[Regulation of insulin release: analysis of the insulin secretory cascade and possible contribution to novel anti-diabetic drug development].
Insulin is the only 'hypoglycemic' hormone synthesized in and secreted from the pancreatic beta cell. Type 2 diabetes results from both secretory failure in the beta cell and insulin resistance in the target tissues for insulin. Attempts to develop anti-diabetic drugs that induce insulin secretion from residual beta cells in type 2 diabetic patients originate from the serendipitous discovery of sulphonylureas as hypoglycemic agents 60 years ago. Generally, secretion is carried out by sequential processes such as granule formation, intracellular traffic, granule docking/priming and the final step, exocytosis (secretory cascade). In the beta cell, recent progress in cell biology enables us to analyze each step in the secretory cascade and to reveal controlling mechanisms. This review describes regulatory mechanisms of insulin release by distinct nutrients, hormones and neurotransmitters, and roles of second messengers and protein phosphorylation in the insulin secretory cascade. Possible development of insulinotropic drugs for the treatment of type 2 diabetes has been also discussed.
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Department of Cell Pharmacology, Nagoya University Postgraduate School of Medicine, Japan.
D003924:Diabetes Mellitus, Type 2 / Q000503:physiopathology; D015195:Drug Design; D005089:Exocytosis; D006728:Hormones / Q000502:physiology; D006801:Humans; D007004:Hypoglycemic Agents; D007328:Insulin / Q000378:metabolism*; D007333:Insulin Resistance; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000378:metabolism*; D018377:Neurotransmitter Agents / Q000502:physiology; D010766:Phosphorylation; D015290:Second Messenger Systems / Q000502:physiology; D013453:Sulfonylurea Compounds
D006728:Hormones; D007004:Hypoglycemic Agents; D007328:Insulin; D018377:Neurotransmitter Agents; D013453:Sulfonylurea Compounds