IRF5 ,artikkeli ajalta ennen pandemiaa Covid-19

 Otan sitaatin tästä luonnollisen immuniteetin alueen tekijästä IRF5, koska se, OGT ja hexosaminisysteemin ylössäätyminen SARS-2 infektiossa assosioituvat  yhteen ja  kliinisesti  havaitaan keuhkoissa  aineksia, joiden koostumuseksessa on kiihtyneellä hexosaminitiellä osuutensa.  Ne eivät ole virusproteiinin tuottamia vaan viruksen  säätämän  ihmismetabolian tuotteita  sillä aikaa kun virus saa replikaatiolleen etuja.  

30 May 2018 : Laboratory Research  

Expression Levels of Interferon Regulatory Factor 5 (IRF5) and Related Inflammatory Cytokines Associated with Severity, Prognosis, and Causative Pathogen in Patients with Community-Acquired Pneumonia

Xiaohong Wang^1ABCDEF, Jia Guo^1BCD, Ying Wang^2BD, Yue Xiao^2AB, Liying Wang^2A, Shucheng Hua^2AG*

DOI: 10.12659/MSM.910756

Med Sci Monit 2018; 24: LBR3620-3630

Authors information Article notes Copyright and License information

Abstract

BACKGROUND: Community-acquired pneumonia (CAP) is a common disease with significant morbidity and mortality. Interferon regulatory factor 5 (IRF5), which induces type I interferons (IFNs) and cytokines such as interleukin (IL)-6, tumor necrosis factor (TNF)-α, IL-10, and interferon gamma-induced protein (IP)10, is a key transcription factor involved in controlling the expression of proinflammatory cytokines and responses to infection. Here, we carefully investigated the role of IRF5 in regulating immune responses to CAP.

MATERIAL AND METHODS: QRT-PCR was used to detect the mRNA levels of IRF5, IL-6, IL-10, IP10, TNF-α, and IFN-α in the peripheral blood of 71 CAP patients and 31 healthy controls, as well as in the bronchoalveolar lavage cells of 20 patients with CAP and 23 patients with lung cancer (using samples from the unaffected lung). Flow cytometry was performed to detect the protein level of IRF5, and a CBA flex set was used to detect the levels of these cytokines in the volunteers.

RESULTS: The expression levels of IRF5 and its related cytokines were significantly increased in CAP patients compared with the controls. Additionally, IRF5, IL-6, IL-10, and IP10 levels were found to be related with the severity of CAP. Furthermore, the levels of IRF5 and IFN-a increased significantly in the early phase of pneumonia caused by influenza virus infection.

CONCLUSIONS: IRF5 and its related inflammatory cytokines are associated with the severity, prognosis, and causative pathogen of CAP patients. This finding may provide new drug targets for the prevention and treatment of severe pneumonia caused by influenza virus.

Keywords: Community-Acquired Infections, Cytokines, Influenza A virus, Interferon Regulatory Factors

OGT geeni pohdittavaksi

 

Aliases for OGT Gene

• GeneCards Symbol: OGT ²
• O-Linked N-Acetylglucosamine (GlcNAc) Transferase ^{2 3 5}
• O-GLCNAC ^{2 3 5}
• HRNT1 ^{2 3 5}
• OGT1 ^{2 3 5}
• O-Linked N-Acetylglucosamine (GlcNAc) Transferase (UDP-N-Acetylglucosamine:Polypeptide-N-Acetylglucosaminyl Transferase) ^{2 3}
• UDP-N-Acetylglucosamine--Peptide N-Acetylglucosaminyltransferase 110 KDa Subunit ^{3 4}
• UDP-N-Acetylglucosamine:Polypeptide-N-Acetylglucosaminyl Transferase ^{2 3}
• O-Linked N-Acetylglucosamine Transferase 110 KDa Subunit ^{3 4}
• O-GlcNAc Transferase Subunit P110 ^{3 4}

• MGC22921 ^{2 5}
• FLJ23071 ^{2 5}
• Uridinediphospho-N-Acetylglucosamine:Polypeptide Beta-N-Acetylglucosaminyl Transferase ³
• O-GlcNAc Transferase P110 Subunit ³
• EC 2.4.1.255 ⁴
• EC 2.4.1.186 ⁴⁸
• HINCUT-1 ³
• EC 2.4.1 ⁴⁸
• XLID106 ³
• MRX106 ³

External Ids for OGT Gene

Entrez Gene Summary for OGT Gene

• This gene encodes a glycosyltransferase that catalyzes the addition of a single N-acetylglucosamine in O-glycosidic linkage to serine or threonine residues. Since both phosphorylation and glycosylation compete for similar serine or threonine residues, the two processes may compete for sites, or they may alter the substrate specificity of nearby sites by steric or electrostatic effects. The protein contains multiple tetratricopeptide repeats that are required for optimal recognition of substrates. Alternatively spliced transcript variants encoding distinct isoforms have been found for this gene. [provided by RefSeq, Oct 2009]

GeneCards Summary for OGT Gene

OGT (O-Linked N-Acetylglucosamine (GlcNAc) Transferase) is a Protein Coding gene. Diseases associated with OGT include Intellectual Developmental Disorder, X-Linked 106 and Myoepithelioma. Among its related pathways are Glucose / Energy Metabolism and Programmed Cell Death. Gene Ontology (GO) annotations related to this gene include identical protein binding and phosphatidylinositol-3,4,5-trisphosphate binding. An important paralog of this gene is TTC16.

UniProtKB/Swiss-Prot Summary for OGT Gene

Catalyzes the transfer of a single N-acetylglucosamine from UDP-GlcNAc to a serine or threonine residue in cytoplasmic and nuclear proteins resulting in their modification with a beta-linked N-acetylglucosamine (O-GlcNAc) (PubMed:26678539, 23103939, 21240259, 21285374, 15361863). Glycosylates a large and diverse number of proteins including histone H2B, AKT1, ATG4B, EZH2, PFKL, KMT2E/MLL5, MAPT/TAU and HCFC1 (PubMed:19451179, 20200153, 21285374, 22923583, 23353889, 24474760, 26678539, 27527864).

 Can regulate their cellular processes via cross-talk between glycosylation and phosphorylation or by affecting proteolytic processing (PubMed:21285374). 

Probably by glycosylating KMT2E/MLL5, stabilizes KMT2E/MLL5 by preventing its ubiquitination (PubMed:26678539). 

Involved in insulin resistance in muscle and adipocyte cells via glycosylating insulin signaling components and inhibiting the 'Thr-308' phosphorylation of AKT1, enhancing IRS1 phosphorylation and attenuating insulin signaling (By similarity)

 Involved in glycolysis regulation by mediating glycosylation of 6-phosphofructokinase PFKL, inhibiting its activity (PubMed:22923583).

 Component of a THAP1 (Znf protein) /THAP3-HCFC1-OGT complex that is required for the regulation of the transcriptional activity of RRM1.

 Plays a key role in chromatin structure by mediating O-GlcNAcylation of 'Ser-112' of histone H2B: recruited to CpG-rich transcription start sites of active genes via its interaction with TET proteins (TET1, TET2 or TET3) (PubMed:22121020, 23353889).

 As part of the NSL complex indirectly involved in acetylation of nucleosomal histone H4 on several lysine residues (PubMed:20018852).

 O-GlcNAcylation of 'Ser-75' of EZH2 increases its stability, and facilitating the formation of H3K27me3 by the PRC2/EED-EZH2 complex (PubMed:24474760).

 Regulates circadian oscillation of the clock genes and glucose homeostasis in the liver. Stabilizes clock proteins ARNTL/BMAL1 and CLOCK through O-glycosylation, which prevents their ubiquitination and subsequent degradation. 

Promotes the CLOCK-ARNTL/BMAL1-mediated transcription of genes in the negative loop of the circadian clock such as PER1/2 and CRY1/2 (PubMed:12150998, 19451179, 20018868, 20200153, 21285374, 15361863).

 O-glycosylates HCFC1 and regulates its proteolytic processing and transcriptional activity (PubMed:21285374, 28584052, 28302723).

 Regulates mitochondrial motility in neurons by mediating glycosylation of TRAK1 (By similarity). Glycosylates HOXA1 (By similarity). 

 O-glycosylates FNIP1 (PubMed:30699359). Promotes autophagy by mediating O-glycosylation of ATG4B (PubMed:27527864). ( OGT1_HUMAN,O15294 )

[Isoform 2]: The mitochondrial isoform (mOGT) is cytotoxic and triggers apoptosis in several cell types including INS1, an insulinoma cell line. ( OGT1_HUMAN,O15294 ) 

 

 

 

Hexosaminitien keskeinen asema 

 https://bmcbiol.biomedcentral.com/articles/10.1186/s12915-019-0671-3

 

Lisääntyvätkö uudet diabetestapaukset covid-19- pandemiasta? Haku: PubMed

3 articles found by citation matching

Increase in the Number of Pediatric New-Onset Diabetes and Diabetic Ketoacidosis Cases During the COVID-19 Pandemic.

Chambers MA, et al. Endocr Pract. 2022. PMID: 35189332 Free PMC article.

Abstract

Objective: Infection with SARS-CoV-2 induces a proinflammatory state that causes hyperglycemia and may precipitate diabetic ketoacidosis (DKA) in patients with known or new-onset diabetes. We examined the trends in new-onset diabetes and DKA prior to and following the onset of the COVID-19 pandemic.Methods: This single-center retrospective observational study included pediatric patients (aged 0 to <18 years) hospitalized with new-onset type 1 diabetes or type 2 diabetes (T2D) before (March 1, 2018, to February 29, 2020) and after (March 1, 2020 to December 31, 2020) the pandemic onset. Demographic, anthropometrics, laboratory and clinical data, and outcomes were obtained. Results: Among 615 children admitted with new-onset diabetes during the entire study period, 401 were admitted before the pandemic onset, and 214 were admitted after the pandemic onset. Children admitted with new-onset diabetes in the postpandemic period were significantly more likely to present with DKA (odds ratio, 1.76; 95% confidence interval, 1.24-2.52) than in the prepandemic phase. Children with DKA after the pandemic onset had higher lengths of hospitalization and were significantly more likely to experience severe DKA (odds ratio, 2.17; 95% confidence interval, 1.34-3.52). A higher proportion of children with DKA admitted to the pediatric intensive care unit required oxygen support after the pandemic onset than before the pandemic onset (8.85% vs 1.92%). Most cases of T2D with DKA occurred following the onset of the pandemic (62.5%). Conclusion: A significant increase in T2D cases occurred following the onset of the COVID-19 pandemic with a greater risk of DKA and severe ketoacidosis. Racial disparity was evident with a higher proportion of Black and American Indian children presenting with ketoacidosis following the pandemic onset.

Keywords: COVID-19; children; diabetes; disparity; ketoacidosis.

 

Increased Severe Cases and New-Onset Type 1 Diabetes Among Children Presenting With Diabetic Ketoacidosis During First Year of COVID-19 Pandemic in Turkey.

Kiral E, et al. Front Pediatr. 2022. PMID: 35844756 Free PMC article. Methods: This is a retrospective multi-center study among 997 children and adolescents with type 1 diabetes who were admitted with DKA to 27 pediatric intensive care units in Turkey between the first year of pandemic and pre-pandemic year. Results: The percentage of children with new-onset Type 1 diabetes presenting with DKA was higher during the COVID-19 pandemic (p < 0.0001). The incidence of severe DKA was also higher during the COVID-19 pandemic (p < 0.0001) and also higher among children with new onset Type 1 diabetes (p < 0.0001). HbA1c levels, duration of insulin infusion, and length of PICU stay were significantly higher/longer during the pandemic period. Eleven patients tested positive for SARS-CoV-2, eight were positive for new onset Type 1 diabetes, and nine tested positive for severe DKA at admission. Discussion: The frequency of new onset of Type 1 diabetes and severe cases among children with DKA during the first year of the COVID-19 pandemic. Furthermore, the cause of the increased severe presentation might be related to restrictions related to the pandemic; however, need to evaluate the potential effects of SARS-CoV-2 on the increased percentage of new onset Type 1 diabetes.

 

The Value of Telemedicine for the Follow-up of Patients with New Onset Type 1 Diabetes Mellitus During COVID-19 Pandemic in Turkey: A Report of Eight Cases.

Evin F, et al. J Clin Res Pediatr Endocrinol. 2021. PMID: 33084289 Free PMC article.The current Coronavirus disease-2019 (COVID-19) pandemic has forced health care teams to look for alternative approaches to manage a great number of children with diabetes, not only in rural but also in urban locations. The aim was to assess the provision of information about follow-up of new-onset pediatric type 1 diabetes (T1D) patients, and to investigate the integration of telemedicine into routine clinical care in the long term. The changes in coefficient of variation (CV), standard deviation and percentages of time in range (TIR), time below range (TBR) and time above range were evaluated in eight children with new-onset T1D, diagnosed during the COVID-19 pandemic. The study period was two-months of follow-up using a telemedicine system. Median follow-up time was 51 (24-66) days. Two of the patients were using low glucose suspend system and six were on multiple daily injection therapy. Target TIR values were achieved in seven patients in the last televisit and, in line with recent guidelines, a TBR <70 mg/dL (<3.9 mmol/L) (level 1 hypoglycemia) of <4% and a TBR <54 mg/dL (<3.0 mmol/L) (level 2 hypoglycemia) of <1% were achieved in all patients. Seven patients achieved a CV of <36% at their last televisit. Telemedicine as an alternative follow-up tool during unusual circumstances such pandemics, even in countries where it is not routinely used, could be beneficial to achieve optimum glycemic control in patients with new-onset T1D.

 

 

2

COVID-19-Induced New-Onset Diabetes: Trends and Technologies.

Metwally AA, Mehta P, Johnson BS, Nagarjuna A, Snyder MP. Diabetes. 2021 Dec;70(12):2733-2744. doi: 10.2337/dbi21-0029. Epub 2021 Oct 22. PMID: 34686519 Free PMC article. Review.

The coronavirus disease 2019 (COVID-19) global pandemic continues to spread worldwide with approximately 216 million confirmed cases and 4.49 million deaths to date. ...Likewise, an increased frequency of diabetes onset and diabetes compl …The coronavirus disease 2019 (COVID-19) global pandemic continues to spread worldwide with approximately 216 million confirmed cases and 4.49 million deaths to date. Intensive efforts are ongoing to combat this disease by suppressing viral transmission, understanding its pathogenesis, developing vaccination strategies, and identifying effective therapeutic targets. Individuals with preexisting diabetes also show higher incidence of COVID-19 illness and poorer prognosis upon infection. Likewise, an increased frequency of diabetes onset and diabetes complications has been reported in patients following COVID-19 diagnosis. COVID-19 may elevate the risk of hyperglycemia and other complications in patients with and without prior diabetes history. It is unclear whether the virus induces type 1 or type 2 diabetes or instead causes a novel atypical form of diabetes. Moreover, it remains unknown if recovering COVID-19 patients exhibit a higher risk of developing new-onset diabetes or its complications going forward. The aim of this review is to summarize what is currently known about the epidemiology and mechanisms of this bidirectional relationship between COVID-19 and diabetes. We highlight major challenges that hinder the study of COVID-19-induced new-onset of diabetes and propose a potential framework for overcoming these obstacles. We also review state-of-the-art wearables and microsampling technologies that can further study diabetes management and progression in new-onset diabetes cases. We conclude by outlining current research initiatives investigating the bidirectional relationship between COVID-19 and diabetes, some with emphasis on wearable technology.

IRF5 geeni .IRF5 on avainasemassa Covid-19 hyperinflammaatiossa. Hexosaminitie säätyy ylös viruksen replikaation eduksi. Calmette-rokotuksen osuus.

Entrez Gene Summary for IRF5 Gene /(7q321)

• This gene encodes a member of the interferon regulatory factor (IRF) family, a group of transcription factors with diverse roles, including virus-mediated activation of interferon, and modulation of cell growth, differentiation, apoptosis, and immune system activity. Members of the IRF family are characterized by a conserved N-terminal DNA-binding domain containing tryptophan (W) repeats. Alternative promoter use and alternative splicing result in multiple transcript variants, and a 30-nt indel polymorphism (SNP rs60344245) can result in loss of a 10-aa segment. [provided by RefSeq, Dec 2016]

GeneCards Summary for IRF5 Gene

IRF5 (Interferon Regulatory Factor 5) is a Protein Coding gene. Diseases associated with IRF5 include Systemic Lupus Erythematosus 10 and Inflammatory Bowel Disease 14. Among its related pathways are TNFR1 Pathway and Senescence and autophagy in cancer. Gene Ontology (GO) annotations related to this gene include DNA-binding transcription factor activity and transcription cis-regulatory region binding. An important paralog of this gene is IRF6.

UniProtKB/Swiss-Prot Summary for IRF5 Gene

Transcription factor that plays a critical role in innate immunity by activating expression of type I interferon (IFN) IFNA and INFB and inflammatory cytokines downstream of endolysosomal toll-like receptors TLR7, TLR8 and TLR9 (PubMed:11303025, 15695821, 22412986, 25326418, 32433612). Regulates the transcription of type I IFN genes (IFN-alpha and IFN-beta) and IFN-stimulated genes (ISG) by binding to an interferon-stimulated response element (ISRE) in their promoters (By similarity). Can efficiently activate both the IFN-beta (IFNB) and the IFN-alpha (IFNA) genes and mediate their induction downstream of the TLR-activated, MyD88-dependent pathway (By similarity). Key transcription factor regulating the IFN response during SARS-CoV-2 infection (PubMed:33440148). ( IRF5_HUMAN,Q13568 )

Protein attributes for IRF5 Gene

Size:498 amino acids

Molecular mass:56044 DaQuaternary structure:

Homodimer, when phosphorylated (PubMed:25326418, 18836453).

• Interacts with TASL (via pLxIS motif); interaction takes place downstream of TLR7, TLR8 or TLR9, leading to its activation (PubMed:32433612).
  Interacts with MYD88 and TRAF6 (By similarity).

 

See this image and copyright information in PMC

Figure 1

Work in progress hypothesis for the hyperinflammatory HBP-GlcNAc-OGT–IRF5-interferon-SARS-CoV-2 pathway leading to the cytokine storm.

 

Working Hypothesis for Glucose Metabolism and SARS-CoV-2 Replication: Interplay Between the Hexosamine Pathway and Interferon RF5 Triggering Hyperinflammation. Role of BCG Vaccine?

Hugo A. Laviada-Molina¹, Irene Leal-Berumen², Ernesto Rodriguez-Ayala³ and Raul A. Bastarrachea^4*

• ^{ONKO BCG  calmettointi  hyödyllinen asia  koronapandemiasta selviämisessä?   Tätä pohdittu seuraavassa artikkelissa vuodelta 2021:}

 https://pubmed.ncbi.nlm.nih.gov/33790587/

 eCollection 2021.

BCG Vaccine-Induced Trained Immunity and COVID-19: Protective or Bystander?

Gopala Koneru  ¹ , Gaber El-Saber Batiha 

 DOI: 10.2147/IDR.S300162 Free PMC article

Abstract

In late 2019, a new virulent coronavirus (CoV) emerged in Wuhan, China and was named as severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). This virus spread rapidly, causing the coronavirus disease-2019 (COVID-19) pandemic. Bacillus Calmette-Guérin (BCG) is a live attenuated tuberculosis (TB) vaccine, associated with induction of non-specific cross-protection against unrelated infections. This protection is a memory-like response in innate immune cells (trained immunity), which is caused by epigenetic reprogramming via histone modification in the regulatory elements of specific genes in monocytes. COVID-19 related epidemiological studies showed an inverse relationship between national BCG vaccination policies and COVID-19 incidence and death, suggesting that BCG may induce trained immunity that could confer some protection against SARS-CoV-2. As this pandemic has put most of Earth's population under quarantine, repurposing of the old, well-characterized BCG may ensure some protection against COVID-19. This review focuses on BCG-related cross-protection and acquisition of trained immunity, as well as the correlation between BCG vaccination and COVID-19 incidence and mortality.

Keywords: BCG vaccine; COVID-19; coronavirus; trained immunity; tuberculosis. 

 

Kommentti: Post-pandemisen vaiheen  kansanterveystyössä olisi mielstäni suositeltavaa käynnistää vanhanaikainen  tubitarkastus eli niitä keuhkoröntgeneitä, koska tubilla ja covidilla on samantapainen  vaikutus immuunikarttaan ja kohde-elimen valintaan.   Ja molempien tautien yhteisvaikutustakin saataa esiintyä.  Ne tavalliset  kylästä kylään rullaavat minithorax-tutkimukset eivät ole mahdotonta toteuttaa. Calmettointikin on  suositeltavaa maailmassa. .

GLP-1 analogeista metabolisen oireyhtymän ja diabeteksen DM2 hoitoon. Semaglutidin kysynnästä obesitashoitoon.

 

Suomen uutisissa mainitaan semaglutide- lääkkeen puute diabeetikoilla, koska lääkettä on alettu käyttää toiseen indikaatioon, obesitas, enenevästi. Kyse on lääkkeen injisoitavasta muodosta. Lääkkeestä on myös tablettimuoto diabeteksen hoitoon. Ruotsissa on 2 valmistetta semaglutidia:

Toinen on suun kautta otettava tablettimuoto.Rybelsus. Toinen on injektiomuoto Ozempic (NovoNordisk), josta Suomen lehdistä mainitsee.

Uutiset https://www.aamulehti.fi/uutiset/art-2000009091964.html

Elintärkeä diabeteslääke loppui Suomen apteekeista, syynä sen suuri suosio laihdutuslääkkeenä – ”Kaikki varastot on myyty loppuun” Ozempicia käytetään tyypin 2 diabeteksessa verensokerin hoitoon. Lääkkeellä on havaittu myös selvästi laihduttava vaikutus, mikä on saanut sen kysynnän rajuun kasvuun syksyn aikana….

• Inkretiinilääkkeiden historiasta muutama artikkeli:

  • Vuodelta 2022 ( semaglutide)

Wegovy (semaglutide): a new weight loss drug for chronic weight management.

Singh G, Krauthamer M, Bjalme-Evans M. J Investig Med. 2022 Jan;70(1):5-13. doi: 10.1136/jim-2021-001952. Epub 2021 Oct 27. PMID: 34706925 Free PMC article. Review.

• Vuodelta 2021 (semaglutide)

Front Endocrinol (Lausanne) 2021 Jul 7;12:645563.

eCollection 2021. Safety of Semaglutide Mark M Smits  1 et al. DOI: 10.3389/fendo.2021.645563 Free PMC article

• Vuodelta 2021 (lixisenatide, exenatide, liraglutide, semaglutide, albiglutide, dulaglutide) https://www.eurekaselect.com/images/graphical-abstract/chyr/17/2/007.jpg

GLP-1RA and SGLT2i: Cardiovascular Impact on Diabetic Patients

Author(s): Aschner Pablo et al. Volume 17, Issue 2, 2021 Published on: 24 November, 2020 DOI: 10.2174/1573402116999201124123549 Background: Diabetes is a chronic disease with high complexity that demands strategic medical care with a multifactorial risk-reduction approach. Over the past decade, the treatment of type 2 diabetes mellitus (T2DM) has entirely changed. One of the paradigm changes has been the arrival of new drugs that reduce cardiovascular risk beyond the reduction of A1C. Objective: Sodium-glucose cotransporter 2 (SGLT2i) and glucagon-like peptide-1 receptor agonist (GLP-1RA) are two groups of antidiabetics drugs, which have demonstrated superiority compared to placebo for major cardiovascular events (MACE).

Methods: We update and discuss their impact on MACE expressed as relative risk (HR hazard ratio) and as the number needed to treat (NNT) to avoid one cardiovascular event in 5 years. We include the publications of the last 10 years. Results: Empagliflozin, Canagliflozin and Dapagliflozin present an HR for MACE of 0.86, 0.86, 0.86 and an NNT of 38, 44, and 33, respectively (Dapagliflozin in secondary prevention). Regarding HHF (Hospitalization for Heart Failure), the HR was 0.65, 0.67, 0.73 and NNT was 44, 62, and 98, respectively. Lixisenatide, Exenatide, Liragutide, Semaglutide, Albiglutide and Dulaglutide presented for MACE an HR of 1.02, 0.91, 0.87, 0.74, 0.78, 0.88, respectively. There was no increase in the risk of HHF, but there was no benefit either. Conclusion: Cardiovascular benefits of the GLP-1RA and the SGLT2i are clinically significant. A number needed to treat under 50 is required to avoid one MACE in five years. These benefits have led to important changes in the Clinical Practice Guidelines and in the care of our patients with T2DM. Keywords: Cardiovascular outcomes, glucose lowering medications, type 2 diabetes mellitus, SGLT2i, GLP1 agonist, cardiovascular mechanisms, cardiovascular disease.

• Vuodelta 2020 ( Semaglutide , dulaglutide, exenatide, liraglutide, lixisenatide)

https://pubmed.ncbi.nlm.nih.gov/31990244/

J Med Econ 2020 Jun;23(6):650-658.

doi: 10.1080/13696998.2020.1722678. Epub 2020 Feb 7. Oral semaglutide versus injectable glucagon-like peptide-1 receptor agonists: a cost of control analysis B B Hansen  1 , S Nuhoho  1 , S N Ali  2 , T Dang-Tan  2 , W J Valentine  3 , S J P Malkin  3 , B Hunt  3 DOI: 10.1080/13696998.2020.1722678 Free article Results: For the treatment target of HbA1c ≤6.5%, once-weekly semaglutide 1 mg and oral semaglutide 14 mg were associated with the lowest costs of control, at USD 15,430 and USD 17,383 per patient achieving target, respectively. Similarly, the cost of control was lowest with once-weekly semaglutide 1 mg at USD 12,627 per patient achieving target, followed by oral semaglutide 14 mg at USD 13,493 per patient achieving target for the target of HbA1c <7.0%. All other interventions were associated with higher cost of control values for both targets. Conclusions: Oral semaglutide 14 mg is likely to be cost-effective versus dulaglutide, exenatide (once weekly and twice daily), liraglutide, and lixisenatide in terms of bringing people with type 2 diabetes to glycemic control targets of HbA1c ≤6.5% and HbA1c <7.0% in the US.

(Bacground: Clinicians have a range of treatment options available to treat people with type 2 diabetes not achieving glycemic control on metformin monotherapy, including modern interventions such as glucagon-like peptide-1 (GLP-1) receptor agonists, sodium-glucose cotransporter-2 (SGLT-2) inhibitors, dipeptidyl peptidase-4 (DPP-4) inhibitors, and older interventions such as thiazolidinediones and sulfonylureas1. GLP-1 receptor agonists are recommended when there is a need to minimize the risk of hypoglycemia, and when there is a need to minimize weight gain or promote weight loss1. Furthermore, GLP-1 receptor agonists with a proven positive impact on the risk of cardiovascular disease are preferred for treatment of patients at high risk of cardiovascular disease1. )

• Vuodelta 2020 (lixisenatide)

Low-dose lixisenatide protects against early-onset nephropathy induced in diabetic rats

2020, Life Sciences

https://www.sciencedirect.com/science/article/abs/pii/S002432052031345X

Lixisenatide, in a low dose regimen, induced a nephroprotective effect evident by significant decreases in serum creatinine and serum urea along with improved renal histology. Low lixisenatide dose showed an antioxidant effect, exhibited by a significant decrease in renal malondialdehyde and total NOx− levels along with a marked rise in total antioxidant capacity. Apart from ameliorating glucose intolerance and insulin resistance, significant down-regulation in renal expressions of iNOS, COX-2, and TGF-B1 were recorded in the diabetic group treated with low dose lixisenatide. Furthermore, low dose lixisenatide was reported to be superior to glimepiride as a nephroprotective. On the contrary, treatment with large dose lixisenatide was founded to be deleterious.

• Vuodelta 2019 kuva (liraglutide, semaglutide)

Figure: GLP-1, liraglutide, semaglutide:

https://www.google.com/url?sa=i&url=https%3A%2F%2Fwww.dovepress.com%2Foral-semaglutide-in-the-management-of-type-2-diabetes-a-report-on-the--peer-reviewed-fulltext-article-DMSO&psig=AOvVaw2JseAF06mq6uzFOGlZnRLQ&ust=1664268015531000&source=images&cd=vfe&ved=0CAkQjRxqFwoTCLiykeqHsvoCFQAAAAAdAAAAABAD

• Vuodelta 2019: Obes Rev 2019 Jun;20(6):805-815.

Epub 2019 Feb 15. Semaglutide as a promising antiobesity drug Georgios A Christou  1 et al. DOI: 10.1111/obr.12839 https://pubmed.ncbi.nlm.nih.gov/30768766/ Semaglutide is a glucagon-like peptide-1 receptor agonist (GLP-1 RA) with a long elimination half-life, allowing subcutaneous (sc) administration once per week. Both the European Medicines Agency (EMA) and the Food and Drug Administration (FDA) recently approved once-weekly sc semaglutide for the treatment of type 2 diabetes mellitus (T2DM). The weight loss efficacy of once-weekly sc semaglutide appears to be superior compared with the other once-weekly GLP-1 RAs in patients with T2DM. Semaglutide was recently evaluated as an antiobesity drug in a phase II dose-finding trial, which demonstrated superior weight loss efficacy of once daily sc semaglutide compared with both placebo and once daily 3.0 mg liraglutide in patients with obesity but without T2DM. The magnitude of semaglutide-induced weight loss in this study exceeded the criteria of both the EMA and FDA for antiobesity drugs, and there were no safety concerns, indicating the eligibility of once daily sc semaglutide as a future antiobesity drug.

• Vuodelta 2019 (liraglutide, semaglutide)

The Discovery and Development of Liraglutide and Semaglutide. Knudsen LB, Lau J. Front Endocrinol (Lausanne). 2019 Apr 12;10:155. doi: 10.3389/fendo.2019.00155. eCollection 2019. PMID: 31031702 Free PMC article. Review. Furthermore, the development of an oral formulation for semaglutide may provide individuals with additional benefits in relation to treatment adherence. In addition to T2D, liraglutide is used in the treatment of obesity, while semaglutide is currently under investi …

• Vuodelta 2018 ( GLP-1RAs, insulin combination)

Am J Med 2018 Nov;131(11):1304-1306.

doi: 10.1016/j.amjmed.2018.05.043. Epub 2018 Jul 2. New Injectable Agents for the Treatment of Type 2 Diabetes Part 2-Glucagon-Like Peptide-1 (GLP-1) Agonists Christa George  1 , AhYoung Byun  2 , Amanda Howard-Thompson  3 Affiliations DOI: 10.1016/j.amjmed.2018.05.043 Abstract The US Food and Drug Administration has recently approved several new glucagon-like peptide-1 (GLP-1) agonists alone and in combination with various insulin products. The second of 2 articles in a series, this review will describe the potential advantages and disadvantages of the GLP-1 agonist class of products. Keywords: GLP-1 combination products; Glucagon like peptide-1 (GLP-1) agonist; Type 2 diabetes.

• Vuodelta 2016 (exenatide, albiglutide, dulaglutide, liraglutide, lixisenatid)

• Vuodelta 2015 informaatiota ruotsalaisesta diabeteslääkehoidon arsenaalista: Mikael Ry´den :Inkretinläkemedel- dyra med oklara läkemedeleffekter (Sida 67) “Det senaste tillskottet I den terapeutiska arsenalen är preparat som påverkar inkretinsystemet. Glukagonlik peptid 1 (GLP-1) är den fysiologiskt kanske viktigaste inkretinen, som verkar genom att öka insulinfrisättningen på intracellulära steg nedom sulfonylureapreparat (SU). Det innebär bl a att GLP-1 stimulerar insulinfrisättningen endast vid förhöjda glukosvärden. Antingen kan man ge subkutana injektioner av GLP-1-analoger (exanatide, liraglutide etc. ) eller perorala preparat som hämmar enzymet dipeptidylpeptidas-4 (DPP4) (sitagliptin etc.) , som bryter ned endogent GLP-1 HbA1c sänks med ca 1 procentenhet med GLP-1-analoger och med 0,7 procentenheter med DPP4-hämmare. GLP-1-analoger förlångsammar även ventrikeltömmningen och kan eventuellt ha effekter på centrala mättnadssystemet. Illamående är vanlig biverkan, men för de patienter som föredrar behandlingen innebär behandlingen med GLP-1-analoger ofta viktnedgång. I kliniska studier har man observerat en viktminskning på ca 3 kg under sex månader, men hos enskilda individer kan effekten vara både större och mindre. DPP-4 hämmare (-gliptiner) är viktneutrala. Det finns ännu inga långtidsstudier på något av dessa preparat, och de är väsentligt dyrare än övriga läkemedel, varför de bör användas restriktivt. Följaktligen bör de betraktas som tredjehandspreparat (prioritet 10 enligt Socialstyrelsen) . En lämplig patient för GLP-1-analoger kan t ex vara en kraftigt obes patient med postprandiala hyperglykemier, där insulin lett eller förväntas leda till utttalada viktuppgång, som kan innebära medicinsk risk. DPP4-hämmare kan övervägas hos patienter som behöver tillägg av perorala antidiabetik men som reagerar med hypoglykemier även på låga elelr måttiga doser av sulfonyureapreparat(SU). Det är viktigt att med dessa nya och dyra preparat utvärdera effekten efter 3-6 månader och seponera preparatet vid utebliven eller otillräcklig effekt.

• Vuodelta 2015 (exenatide)

Epub 2015 Nov 11. The value of short- and long-acting glucagon-like peptide-1 agonists in the management of type 2 diabetes mellitus: experience with exenatide

Xiao-Hui Guo  1

DOI: 10.1185/03007995.2015.1103214 Abstract

Background: Only about half of patients with type 2 diabetes treated with antihyperglycemic drugs achieve glycemic control (HbA1c <7%), most commonly due to poor treatment adherence. Glucagon-like peptide-1 (GLP-1) receptor agonists act on multiple targets involved in glucose homeostasis and have a low risk of causing hypoglycemia. While GLP-1 receptor (GLP-1R) agonists (GLP-1RA) share the same mechanism of action, clinical profiles of individual agents differ, particularly between short- and long-acting agents.

In this article, recent findings regarding the pharmacology of GLP-1 agonists are reviewed, and the clinical effects of short- versus long-acting agents are compared.Data sources: Relevant articles were identified through a search of PubMed using the keywords glucagon-like peptide-1, GLP-1, glucagon-like peptide-1 receptor agonist, GLP-1R agonist, and exenatide for publications up to 22 May 2015. Supporting data were obtained from additional searches for e as well as from the bibliographies of key articles.Findings: Short-acting GLP-1R agonists produce greater reductions in postprandial glucose levels by slowing gastric emptying, whereas long-acting GLP-1R agonists produce greater reductions in fasting blood glucose by stimulating insulin secretion from the pancreas. These characteristics can be exploited to provide individualized treatment to patients. A large body of evidence supports the benefits of short- and long-acting exenatide as add-on therapy in patients with inadequate glycemic control despite maximum tolerated doses of metformin and/or sulfonylurea. Exenatide is generally well tolerated and no new safety concerns were identified during long-term follow-up of up to 5 years. A limitation of this review of short-and long-acting GLP-1 receptor agonists is that it focuses on exenatide rather than all the drugs in this class. However, the focus on a single molecule helps to avoid any confusion that may be introduced as a result of differences in molecular structure and size.Conclusions: Short-acting GLP-1R agonists including exenatide are well suited to patients with type 2 diabetes with exaggerated postprandial glucose excursions and for co-administration with basal insulin therapy. Long-acting GLP-1R agonists including once weekly exenatide offer greater convenience and are well suited to patients who require specific control of fasting hyperglycemia.

Keywords: Exenatide; GLP-1; Glucagon-like peptide-1; Hyperglycemia; Hypoglycemia; Review; Type 2 diabetes

• Vuodelta 2014 (GLP1 reseptoriagonisti- insuliini-kombinaatio)

Insulin and glucagon-like peptide receptor agonist (GLP 1 RA) combinations. Kalra S. J Pak Med Assoc. 2014 Mar;64(3):359-61. PMID: 24864619 Review.

• Vuodelta 2013 (lixisenatide , exenatide )

Rosenstock J .Raccah D ,Koranyi L et al. Efficacy and safety of lixisenatide once daily versus exenatide twice daily in type 2 diabetes inadequately controlled on metformin (Get Goal-X).Diabetes Care. 2013; 36: 2945-2951

• Vuodelta 2012 (exenatide, liraglutide)

(Drug Administration: exenatide twice daily and liraglutide once daily. Several additional GLP-1 agonists, including exenatide LAR, albiglutide, and taspoglutide, are in various stages of clinical trials and have been modified to increase their half-lives). Clinical efficacy and safety of once-weekly glucagon-like peptide-1 agonists in development for treatment of type 2 diabetes mellitus in adults. Tzefos M, Harris K, Brackett A. Ann Pharmacother. 2012 Jan;46(1):68-78. doi: 10.1345/aph.1Q379. PMID: 22232377 Review.

• Vuodelta 2012 (Liraglutide)

.2012 Oct;28(4):436-44.

doi: 10.1017/S0266462312000608. Epub 2012 Sep 24. Cost-utility analysis of liraglutide versus glimepiride as add-on to metformin in type 2 diabetes patients in China

• Vuodelta 2011 (Liraglutide, exenatide)

https://pubmed.ncbi.nlm.nih.gov/21609656/

Liraglutide for the treatment of type 2 diabetes D Shyangdan  1 , E Cummins, P Royle, N Waugh Affiliations DOI: 10.3310/hta15suppl1/09 Health Technol Assess 2011 May;15 Suppl 1:77-86. doi: Two doses of liraglutide, 1.2 and 1.8 mg, were used in some trials, but in the two comparisons in triple therapy, against glargine and exenatide, only the 1.8-mg dose was used. Liraglutide in both doses was found to be clinically effective in lowering blood glucose concentration [glycated haemoglobin (HbA1c)], reducing weight (unlike other glucose-lowering agents, such as sulphonylureas, glitazones and insulins, which cause weight gain) and also reducing systolic blood pressure (SBP). Hypoglycaemia was uncommon.

Sinkkihomeostaasin geeniperheistä ZNT ja ZIP. Perhe ZNT, 10 jäsentä.

Kaksi proteiiniperhettä SLC30A (ZNT) ja SLC39A (ZIP) osallistuvat sinkin homeostaasiin.Sinkillä on merkitys glukoosiaineenvaihdunnalle.
https://pubmed.ncbi.nlm.nih.gov/29372370/?from_term=SLC30A+family&from_pos=1

ZNT geeni perhe

(1) Zinc Transporter 1, SLC30, ZNT(1q32.3)

Sinkinpuute tyyppi. Acrodermatitis enteropathica.

https://www.genecards.org/cgi-bin/carddisp.pl?gene=SLC30A1&keywords=ZNT1 GeneCards Summary for SLC30A1 Gene

SLC30A1 (Solute Carrier Family 30 Member 1) is a Protein Coding gene. Diseases associated with SLC30A1 include Epidermodysplasia Verruciformis 1 and Acrodermatitis Enteropathica, Zinc-Deficiency Type. Among its related pathways are Mineral absorption and Metal ion SLC transporters. Gene Ontology (GO) annotations related to this gene include cation transmembrane transporter activity and calcium channel inhibitor activity. An important paralog of this gene is SLC30A10. UniProtKB/Swiss-Prot Summary for SLC30A1 Gene: May be involved in zinc transport out of the cell. ZNT1_HUMAN,Q9Y6M5

(2) Zinc transporter 2 (1p36.11) , ZNT2, SLC30A2, TNZD, PP12488.

https://www.genecards.org/cgi-bin/carddisp.pl?gene=SLC30A2&keywords=ZNT2

(Sinkin erittyminen äidinmaitoon. Sinkinpuute tyyppi).

The protein encoded by this gene is a zinc transporter that acts as a homodimer. The encoded protein plays a role in secreting zinc into breast milk. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2015]

SLC30A2 (Solute Carrier Family 30 Member 2) is a Protein Coding gene. Diseases associated with SLC30A2 include Zinc Deficiency, Transient Neonatal and Acrodermatitis Enteropathica, Zinc-Deficiency Type. Among its related pathways are Metal ion SLC transporters and Transport of glucose and other sugars, bile salts and organic acids, metal ions and amine compounds. Gene Ontology (GO) annotations related to this gene include cation transmembrane transporter activity. An important paralog of this gene is SLC30A3.

(3) ZNT3, SCL30A3 ( 2p23.3)

https://www.genecards.org/cgi-bin/carddisp.pl?gene=SLC30A3&keywords=ZNT3

GeneCards Summary for SLC30A3 Gene

SLC30A3 (Solute Carrier Family 30 Member 3) is a Protein Coding gene. Diseases associated with SLC30A3 include Hyperekplexia. Among its related pathways are Metal ion SLC transporters and Transport of glucose and other sugars, bile salts and organic acids, metal ions and amine compounds. Gene Ontology (GO) annotations related to this gene include cation transmembrane transporter activity and zinc-transporting ATPase activity. An important paralog of this gene is SLC30A2. UniProtKB/Swiss-Prot Summary for SLC30A3 Gene Involved in accumulation of zinc in synaptic vesicles. ZNT3_HUMAN,Q99726

(4) ZNT4 , SLC30A4(15q21.1)

https://www.genecards.org/cgi-bin/carddisp.pl?gene=SLC30A4&keywords=ZNT4 Zinc is the second most abundant trace metal in the human body. It is an essential element, serving both a structural role, as in the formation of zinc fingers in DNA-binding proteins, and a catalytic role in metalloenzymes, such as pancreatic carboxypeptidases (e.g., MIM 114852), alkaline phosphatases (e.g., MIM 171760), various dehydrogenases, and superoxide dismutases (e.g., MIM 147450). SLC30A4, or ZNT4, belongs to the ZNT family of zinc transporters. ZNTs are involved in transporting zinc out of the cytoplasm and have similar structures, consisting of 6 transmembrane domains and a histidine-rich cytoplasmic loop (Huang and Gitschier, 1997 [PubMed 9354792]).[supplied by OMIM, Mar 2008] GeneCards Summary for SLC30A4 Gene SLC30A4 (Solute Carrier Family 30 Member 4) is a Protein Coding gene. Diseases associated with SLC30A4 include Acrodermatitis Enteropathica, Zinc-Deficiency Type and Acrodermatitis. Among its related pathways are Metal ion SLC transporters. Gene Ontology (GO) annotations related to this gene include cation transmembrane transporter activity and zinc ion transmembrane transporter activity. An important paralog of this gene is SLC30A2. Probably involved in zinc transport out of the cytoplasm, maybe by sequestration into an intracellular compartment. ZNT4_HUMAN,O14863

(5) ZNT5 (SLC30A5) (5q13.1-q13.29 , ZNTL1, HZTL1

https://www.genecards.org/cgi-bin/carddisp.pl?gene=SLC30A5&keywords=ZNT5 Entrez Gene Summary for SLC30A5 Gene This gene encodes a member of the SLC30A/ZnT family of zinc transporter proteins. ZnT proteins mediate both cellular zinc efflux and zinc sequestration into membrane-bound organelles. The encoded protein plays a role in the early secretory pathway as a heterodimer with zinc transporter 6, and may also regulate zinc sequestration into secretory granules of pancreatic beta cells. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene, and a pseudogene of this gene is located on the long arm of chromosome 19. [provided by RefSeq, Oct 2011] GeneCards Summary for SLC30A5 Gene SLC30A5 (Solute Carrier Family 30 Member 5) is a Protein Coding gene. Diseases associated with SLC30A5 include Acrodermatitis Enteropathica, Zinc-Deficiency Type and Nonsyndromic Deafness. Among its related pathways are Metal ion SLC transporters and Peptide hormone metabolism. Gene Ontology (GO) annotations related to this gene include cation transmembrane transporter activity and zinc ion transmembrane transporter activity. An important paralog of this gene is SLC30A7. UniProtKB/Swiss-Prot Summary for SLC30A5 Gene Functions as a zinc transporter. May be a transporter of zinc into beta cells in order to form insulin crystals. Partly regulates cellular zinc homeostasis. Required with ZNT7 for the activation of zinc-requiring enzymes, alkaline phosphatases (ALPs). Transports zinc into the lumens of the Golgi apparatus and vesicular compartments where ALPs locate, thus, converting apoALPs to holoALPs. Required with ZNT6 and ZNT7 for the activation of TNAP. ZNT5_HUMAN,Q8TAD4

(6) ZNT6, SLC30A6, (2p22.3), MST103, MSTP103.

https://www.genecards.org/cgi-bin/carddisp.pl?gene=SLC30A6&keywords=ZNT6 Entrez Gene Summary for SLC30A6 Gene This gene encodes a member of a family of proteins that function as zinc transporters. This protein can regulate subcellular levels of zinc in the Golgi and vesicles. Expression of this gene is altered in the Alzheimer's disease brain plaques. [provided by RefSeq, Aug 2016] GeneCards Summary for SLC30A6 Gene SLC30A6 (Solute Carrier Family 30 Member 6) is a Protein Coding gene. Diseases associated with SLC30A6 include Alzheimer Disease and Myasthenic Syndrome, Congenital, 5. Among its related pathways are Metal ion SLC transporters and Peptide hormone metabolism. Gene Ontology (GO) annotations related to this gene include cation transmembrane transporter activity and zinc ion transmembrane transporter activity. An important paralog of this gene is SLC30A5. UniProtKB/Swiss-Prot Summary for SLC30A6 Gene Zinc-efflux transporter which allocates the cytoplasmic zinc to the trans-Golgi network (TGN) as well as the vesicular compartment. ZNT6_HUMAN,Q6NXT4

(7) ZNT7, SLC30A7 . Zinc transporter like 2, ZNTL2.

https://www.genecards.org/cgi-bin/carddisp.pl?gene=SLC30A7&keywords=ZNT7Entrez Gene Summary for SLC30A7 Gene. Zinc functions as a cofactor for numerous enzymes, nuclear factors, and hormones and as an intra- and intercellular signal ion. Members of the zinc transporter (ZNT)/SLC30 subfamily of the cation diffusion facilitator family, such as SLC30A7, permit cellular efflux of zinc (Seve et al., 2004 [PubMed 15154973]).[supplied by OMIM, Mar 2008] GeneCards Summary for SLC30A7 Gene

SLC30A7 (Solute Carrier Family 30 Member 7) is a Protein Coding gene. Diseases associated with SLC30A7 include Joubert Syndrome 1 and Acrodermatitis Enteropathica, Zinc-Deficiency Type. Among its related pathways are Metal ion SLC transporters and Peptide hormone metabolism. Gene Ontology (GO) annotations related to this gene include cation transmembrane transporter activity. An important paralog of this gene is SLC30A5. UniProtKB/Swiss-Prot Summary for SLC30A7 Gene Seems to facilitate zinc transport from the cytoplasm into the Golgi apparatus. Partly regulates cellular zinc homeostasis. Required with ZNT5 for the activation of zinc-requiring enzymes, alkaline phosphatases (ALPs). Transports zinc into the lumens of the Golgi apparatus and the vesicular compartments where ALPs locate, thus, converting apoALPs to holoALPs. Required with ZNT5 and ZNT6 for the activation of TNAP (By similarity). ZNT7_HUMAN,Q8NEW0
 

(8), ZNT8, SLC30A8, (8q24.11)

https://www.genecards.org/cgi-bin/carddisp.pl?gene=SLC30A8&keywords=ZNT8 Entrez Gene Summary for SLC30A8 Gene. The protein encoded by this gene is a zinc efflux transporter involved in the accumulation of zinc in intracellular vesicles. This gene is expressed at a high level only in the pancreas, particularly in islets of Langerhans. The encoded protein colocalizes with insulin in the secretory pathway granules of the insulin-secreting INS-1 cells. Allelic variants of this gene exist that confer susceptibility to diabetes mellitus, noninsulin-dependent (NIDDM). Several transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Mar 2010]. GeneCards Summary for SLC30A8 Gene. SLC30A8 (Solute Carrier Family 30 Member 8) is a Protein Coding gene. Diseases associated with SLC30A8 include Diabetes Mellitus, Noninsulin-Dependent and Diabetes Mellitus. Among its related pathways are Metal ion SLC transporters and Peptide hormone metabolism. Gene Ontology (GO) annotations related to this gene include protein homodimerization activity and zinc ion transmembrane transporter activity. An important paralog of this gene is SLC30A2. UniProtKB/Swiss-Prot Summary for SLC30A8 Gene. Facilitates the accumulation of zinc from the cytoplasm into intracellular vesicles, being a zinc-efflux transporter. May be a major component for providing zinc to insulin maturation and/or storage processes in insulin-secreting pancreatic beta-cells. ZNT8_HUMAN,Q8IWU4

(9) ZNT9, SLC30A9.(4p13), GRIP1- dependent Nuclear Receptor Coactivator, GAC63, Chromosome4 OREF1, BILAPES, HuEL.
 GeneCards Summary for SLC30A9 Gene

SLC30A9 (Solute Carrier Family 30 Member 9) is a Protein Coding gene. Diseases associated with SLC30A9 include Birk-Landau-Perez Syndrome and Hemochromatosis, Type 5. Among its related pathways are Metal ion SLC transporters. Gene Ontology (GO) annotations related to this gene include DNA-binding transcription factor activity and nuclear receptor transcription coactivator activity. UniProtKB/Swiss-Prot Summary for SLC30A9 Gene Acts as a zinc transporter involved in intracellular zinc homeostasis (PubMed:28334855). Functions as a secondary coactivator for nuclear receptors by cooperating with p160 coactivators subtypes. Plays a role in transcriptional activation of Wnt-responsive genes (By similarity). ZNT9_HUMAN,Q6PML9 Quaternary structure: Interacts with GRIP1, ESR1 and AR.

(10) ZNT10, SLC30A10, (1q41), Manganese Transporter SLC30 A19, HMNDYT1, HMDPC, ZRC1, ZNT8.
Entrez Gene Summary for SLC30A10 Gene This gene is highly expressed in the liver and is inducible by manganese. Its protein product appears to be critical in maintaining manganese levels, and has higher specificity for manganese than zinc. Loss of function mutations appear to result in a pleomorphic phenotype, including dystonia and adult-onset parkinsonism. Alternatively spliced transcript variants have been observed for this gene. [provided by RefSeq, Mar 2012]GeneCards Summary for SLC30A10 Gene SLC30A10 (Solute Carrier Family 30 Member 10) is a Protein Coding gene. Diseases associated with SLC30A10 include Hypermanganesemia With Dystonia 1 and Hypermanganesemia With Dystonia. Among its related pathways are Metal ion SLC transporters. Gene Ontology (GO) annotations related to this gene include cation transmembrane transporter activity. An important paralog of this gene is SLC30A1. UniProtKB/Swiss-Prot Summary for SLC30A10 Gene. Plays a pivotal role in manganese transport. Manganese is an essential cation for the function of several enzymes, including some crucially important for the metabolism of neurotransmitters and other neuronal metabolic pathways. However, elevated levels of manganese are cytotoxic and induce oxidative stress, mitochondrial dysfunction and apoptosis. Acts as manganese efflux transporter and confers protection against manganese-induced cell death (PubMed:22341972, PubMed:22341971, PubMed:25319704, PubMed:27226609, PubMed:27307044). Also acts as zinc transporter involved in zinc homeostasis. Seems to mediate zinc transport into early endosomes and recycling endosomes to prevent zinc toxicity; the function may be regulated by heterodimerization with other zinc transporters of the SLC30A subfamily. The SLC30A3:SLC30A10 heterodimer is involved in zinc transport-dependent regulation of the EGFR/ERK transduction pathway in endosomes. May be involved in regulation of zinc-dependent senescence of vascular smooth muscle cells (PubMed:22706290, PubMed:22427991, PubMed:26728129). ZNT10_HUMAN,Q6XR72 Protein attributes for SLC30A10 Gene Size: 485 amino acids , Molecular mass: 52684 Da . Quaternary structure: Forms homodimers. Forms heterodimers and high-molecular weight oligomers with SLC30A3, SLC30A2 and SLC30A4; heterodimerization is mediated by covalent-bound tyrosine residues and occurs probably in a tissue-specific manner. Miscellaneous: [Isoform 2]: May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay. SequenceCaution: Sequence=AAP44332.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Sequence of unknown origin in position 427.; Evidence={ECO:0000305};

(11) ZNT tästä eteenpäin ei löydy geenejä tällä perhenimellä  SLC30A.
9.6. 2020 ZNT perheen geeneistä Gene Cards lähteestä. hakusanana  ZNT , numerot 1-10 tai  SCL30A numerot 1-10.
Klo 12:02.