Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01275 (glucagon)
 26,492 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The impact of modest but prolonged (3 h) exposure to high physiological glucose concentrations and hyperkalemia on the insulin secretory and phospholipase C (PLC) responses of rat pancreatic islets was determined. In acute studies, glucose (5-20 mM) caused a dose-dependent increase in secretion with maximal release rates 25-fold above basal secretion. When measured after 3 h of exposure to 5-10 mM glucose, subsequent stimulation of islets with 10-20 mM glucose during a dynamic perifusion resulted in dose-dependent decrements in secretion and PLC activation. Acute hyperkalemia (15-30 mM) stimulated calcium-dependent increases in both insulin secretion and PLC activation; however, prolonged hyperkalemia resulted in a biochemical and secretory lesion similar to that induced by sustained modest hyperglycemia. Glucose- (8 mM) desensitized islets retained significant sensitivity to stimulation by either carbachol or glucagon-like peptide-1. These findings emphasize the vulnerability of the beta-cell to even moderate sustained hyperglycemia and provide a biochemical rationale for achieving tight glucose control in diabetic patients. They also suggest that PLC activation plays a critically important role in the physiological regulation of glucose-induced secretion and in the desensitization of release that follows chronic hyperglycemia or hyperkalemia.
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PMID:Desensitization of the pancreatic beta-cell: effects of sustained physiological hyperglycemia and potassium. 1686 27