Abstract
Fructose stimulates vasopressin in humans
and can be generated endogenously by activation of the polyol pathway
with hyperosmolarity.
We hypothesized that fructose metabolism in the hypothalamus might partly control vasopressin responses after acute dehydration.
Wild-type and fructokinase-knockout mice were deprived of water for 24 h. The supraoptic nucleus was evaluated for vasopressin and markers of the aldose reductase-fructokinase pathway. The posterior pituitary vasopressin and serum copeptin levels were examined. Hypothalamic explants were evaluated for vasopressin secretion in response to exogenous fructose. Water restriction increased serum and urine osmolality and serum copeptin in both groups of mice, although the increase in copeptin in wild-type mice was larger than that in fructokinase-knockout mice. Water-restricted, wild-type mice showed an increase in vasopressin and aldose reductase mRNA, sorbitol, fructose and uric acid in the supraoptic nucleus. In contrast, fructokinase-knockout mice showed no change in vasopressin or aldose reductase mRNA, and no changes in sorbitol or uric acid, although fructose levels increased. With water restriction, vasopressin in the pituitary of wild-type mice was significantly less than that of fructokinase-knockout mice, indicating that fructokinase-driven vasopressin secretion overrode synthesis. Fructose increased vasopressin release in hypothalamic explants that was not observed in fructokinase-knockout mice. In situ hybridization documented fructokinase mRNA in the supraoptic nucleus, paraventricular nucleus and suprachiasmatic nucleus. Acute dehydration activates the aldose reductase-fructokinase pathway in the hypothalamus and partly drives the vasopressin response. Exogenous fructose increases vasopressin release in hypothalamic explants dependent on fructokinase. Nevertheless, circulating vasopressin is maintained and urinary concentrating is not impaired.
Abstract
Fructose stimulates vasopressin in humans
and can be generated endogenously by activation of the polyol pathway
with hyperosmolarity. We hypothesized that fructose metabolism in the
hypothalamus might partly control vasopressin responses after acute dehydration.
Wild-type and fructokinase-knockout mice were deprived of water for 24
h. The supraoptic nucleus was evaluated for vasopressin and markers of
the aldose reductase-fructokinase pathway. The posterior pituitary
vasopressin and serum copeptin levels were examined. Hypothalamic
explants were evaluated for vasopressin secretion in response
to exogenous fructose. Water restriction increased serum and urine
osmolality and serum copeptin in both groups of mice, although the
increase in copeptin in wild-type mice was larger than that in
fructokinase-knockout mice. Water-restricted, wild-type mice showed an
increase in vasopressin and aldose reductase mRNA, sorbitol, fructose
and uric acid in the supraoptic nucleus. In contrast,
fructokinase-knockout mice showed no change in vasopressin or aldose
reductase mRNA, and no changes in sorbitol or uric acid, although
fructose levels increased. With water restriction, vasopressin in the
pituitary of wild-type mice was significantly less than that of
fructokinase-knockout mice, indicating that fructokinase-driven
vasopressin secretion overrode synthesis. Fructose increased vasopressin
release in hypothalamic explants that was not observed in
fructokinase-knockout mice. In situ hybridization documented
fructokinase mRNA in the supraoptic nucleus, paraventricular nucleus and
suprachiasmatic nucleus. Acute dehydration activates the aldose reductase-fructokinase pathway in the hypothalamus and partly drives the vasopressin response.
Exogenous fructose increases vasopressin release in hypothalamic
explants dependent on fructokinase. Nevertheless, circulating
vasopressin is maintained and urinary concentrating is not impaired.
NEW & NOTEWORTHY:
This study increases our understanding of the mechanisms leading to vasopressin release under conditions of water restriction (acute dehydration). Specifically, these studies suggest that the aldose reductase-fructokinase pathways may be involved in vasopressin synthesis in the hypothalamus and secretion by the pituitary in response to acute dehydration. Nevertheless, mice undergoing water restriction remain capable of maintaining sufficient vasopressin (copeptin) levels to allow normal urinary concentration. Further studies of the aldose reductase-fructokinase system in vasopressin regulation appear indicated.
Copyright © 2017 the American Physiological Society.
KEYWORDS:
aldose reductase; dehydration; fructokinase; fructose; uric acid; vasopressinWe hypothesized that fructose metabolism in the hypothalamus might partly control vasopressin responses after acute dehydration.
Wild-type and fructokinase-knockout mice were deprived of water for 24 h. The supraoptic nucleus was evaluated for vasopressin and markers of the aldose reductase-fructokinase pathway. The posterior pituitary vasopressin and serum copeptin levels were examined. Hypothalamic explants were evaluated for vasopressin secretion in response to exogenous fructose. Water restriction increased serum and urine osmolality and serum copeptin in both groups of mice, although the increase in copeptin in wild-type mice was larger than that in fructokinase-knockout mice. Water-restricted, wild-type mice showed an increase in vasopressin and aldose reductase mRNA, sorbitol, fructose and uric acid in the supraoptic nucleus. In contrast, fructokinase-knockout mice showed no change in vasopressin or aldose reductase mRNA, and no changes in sorbitol or uric acid, although fructose levels increased. With water restriction, vasopressin in the pituitary of wild-type mice was significantly less than that of fructokinase-knockout mice, indicating that fructokinase-driven vasopressin secretion overrode synthesis. Fructose increased vasopressin release in hypothalamic explants that was not observed in fructokinase-knockout mice. In situ hybridization documented fructokinase mRNA in the supraoptic nucleus, paraventricular nucleus and suprachiasmatic nucleus. Acute dehydration activates the aldose reductase-fructokinase pathway in the hypothalamus and partly drives the vasopressin response. Exogenous fructose increases vasopressin release in hypothalamic explants dependent on fructokinase. Nevertheless, circulating vasopressin is maintained and urinary concentrating is not impaired.
NEW & NOTEWORTHY:
This study increases our understanding of the mechanisms leading to vasopressin release under conditions of water restriction (acute dehydration). Specifically, these studies suggest that the aldose reductase-fructokinase pathways may be involved in vasopressin synthesis in the hypothalamus and secretion by the pituitary in response to acute dehydration. Nevertheless, mice undergoing water restriction remain capable of maintaining sufficient vasopressin (copeptin) levels to allow normal urinary concentration. Further studies of the aldose reductase-fructokinase system in vasopressin regulation appear indicated.
Copyright © 2017 the American Physiological Society.
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