The unique innervation pattern of the human islets of Langerhans has been described in two articles in the Nature Medicine and Cell Metabolism. These results will have major implications for future development of novel drugs for the treatment of diabetes.
Hormone release by the endocrine pancreas is regulated by the autonomic, non-voluntarily, nervous system, consisting of parasympathetic and sympathetic nerves.
Until now the interplay between the nervous system and hormone releasing cells of the human endocrine pancreas has been unclear.
Professor Per-Olof Berggren’s research group has now discovered that the human islet is only scarcely innervated by acetylcholine releasing parasympathetic nerves.
Instead, this regulating neurotransmitter substance is released by the glucagon producing alpha-cells.
Moreover, the sympathetic system innervates the smooth muscle cells of the blood vessels instead of endocrine cells. This implies indirect control of hormone release following changes in blood flow.
The findings of the unique innervation patterns are important for development of novel pharmacological strategies in the treatment of diabetes and its complications.
Read more:
- Alpha cells secrete acetylcholine as a non-neuronal paracrine signal priming beta cell function in humans. Rodriguez-Diaz R et.al. Nat Med. 2011, June; 17(7):888-92
- Autonomic axons in the human endocrine pancreas show unique innervation patterns. Rodriguez-Diaz R, Abdulreda MH, Formoso AL, Gans I, Ricordi C, Berggren P-O and Caicedo A. Cell Metabolism, July 2011
- KOLINERGINEN SIGNALOINTI Haimasaarekkeessa:
Diabetes. 2014 Aug;63(8):2714-26. doi: 10.2337/db13-1371. Epub 2014 Mar 21.
Control of insulin secretion by cholinergic signaling in the human pancreatic islet. Molina J1, Rodriguez-Diaz R2, Fachado A3, Jacques-Silva MC3, Berggren PO4, Caicedo A5.
Tutkijat havaitsivat, että endogeeninen AK stimuloi INSULIINIA erittäviä Beta-soluja muskarinireseptoreitten M3 ja M5 välityksellä ja lisäksi sSOMATOSTATIINIA erittäviä D-soluja M1- reseptorin kautta.
Koska SOMATOSTATIINI on vahva inhibiittori INSULIINI-eritykselle, tutkijat tekivät hypoteesin, että kolinerginen INPUT D-soluihin epäsuorasti säätelee Beta-solufunktiota.
Todellakin kun kaikki muskariiniset signaalit oli blokeerattu, SOMATOSTATIINI-eritys laski ja INSULIINI-eritys odottamatta liääntyi viitaten siihen, että estävä ( inhibitorinen) INPUT Beta-soluihin vähentyi. Endogeeninen kolinerginen signalointi antaa siten stimuloivaa ja epäsuorasti inhiboivaa INPUT virtaa Beta-soluihin säädellen ihmisen saarekkeiden INSULIINI-eritysta.
- Acetylcholine regulates hormone secretion from the pancreatic islet and is thus crucial for glucose homeostasis. Little is known, however, about acetylcholine (cholinergic) signaling in the human islet. We recently reported that in the human islet, acetylcholine is primarily a paracrine signal released from α-cells rather than primarily a neural signal as in rodent islets. In this study, we demonstrate that the effects acetylcholine produces in the human islet are different and more complex than expected from studies conducted on cell lines and rodent islets. We found that endogenous acetylcholine not only stimulates the insulin-secreting β-cell via the muscarinic acetylcholine receptors M3 and M5, but also the somatostatin-secreting δ-cell via M1 receptors. Because somatostatin is a strong inhibitor of insulin secretion, we hypothesized that cholinergic input to the δ-cell indirectly regulates β-cell function. Indeed, when all muscarinic signaling was blocked, somatostatin secretion decreased and insulin secretion unexpectedly increased, suggesting a reduced inhibitory input to β-cells. Endogenous cholinergic signaling therefore provides direct stimulatory and indirect inhibitory input to β-cells to regulate insulin secretion from the human islet.
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