Rapid insulinotropic effect of 17beta-estradiol via a plasma membrane receptor.
Impaired insulin secretion is a hallmark in both type I and type II diabetic individuals. Whereas type I (insulin-dependent diabetes mellitus) implies ss-cell destruction, type II (non-insulin dependent diabetes mellitus), responsible for 75% of diabetic syndromes, involves diminished glucose-dependent secretion of insulin from pancreatic beta-cells. Although a clear demonstration of a direct effect of 17beta-estradiol on the pancreatic ss-cell is lacking, an in vivo insulinotropic effect has been suggested. In this report we describe the effects of 17beta-estradiol in mouse pancreatic ss-cells. 17beta-Estradiol, at physiological concentrations, closes K(ATP) channels, which are also targets for antidiabetic sulfonylureas, in a rapid and reversible manner. Furthermore, in synergy with glucose, 17beta-estradiol depolarizes the plasma membrane, eliciting electrical activity and intracellular calcium signals, which in turn enhance insulin secretion. These effects occur through a receptor located at the plasma membrane, distinct from the classic cytosolic estrogen receptor. Specific competitive binding and localization of 17beta-estradiol receptors at the plasma membrane was demonstrated using confocal reflective microscopy and immunocytochemistry. Gaining deeper knowledge of the effect induced by 17beta-estradiol may be important in order to better understand the hormonal regulation of insulin secretion and for the treatment of NIDDM. receptor.
Institute of Bioengineering and Department of Physiology, Miguel Hernández University, San Juan Campus, Alicante, Spain. nadal@umh.es
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Nadal
J M
JM
Rovira
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Laribi
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Leon-quinto
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Andreu
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Ripoll
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Soria
D018528:ATP-Binding Cassette Transporters; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001667:Binding, Competitive; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000378:metabolism; D002463:Cell Membrane Permeability; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007124:Immunoenzyme Techniques; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D017136:Ion Transport / Q000187:drug effects; D007515:Islets of Langerhans / Q000187:drug effects* / Q000378:metabolism; D054086:KATP Channels; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D008565:Membrane Proteins / Q000187:drug effects* / Q000502:physiology; D051379:Mice; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence; D018408:Patch-Clamp Techniques; D011188:Potassium / Q000378:metabolism*; D015221:Potassium Channels / Q000378:metabolism*; D024661:Potassium Channels, Inwardly Rectifying; D011959:Receptors, Estradiol / Q000187:drug effects* / Q000502:physiology; D015398:Signal Transduction; D013453:Sulfonylurea Compounds / Q000494:pharmacology
D018528:ATP-Binding Cassette Transporters; D015220:Calcium Channels; D007004:Hypoglycemic Agents; D007328:Insulin; D054086:KATP Channels; D008565:Membrane Proteins; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; D011959:Receptors, Estradiol; D013453:Sulfonylurea Compounds; C092520:uK-ATP-1 potassium channel; D004958:Estradiol; D000255:Adenosine Triphosphate; D011188:Potassium; D002118:Calcium