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.
Nadal
A
A
Institute of Bioengineering and Department of Physiology, Miguel Hernández University, San Juan Campus, Alicante, Spain. nadal@umh.es
Rovira
J M
JM
Laribi
O
O
Leon-quinto
T
T
Andreu
E
E
Ripoll
C
C
Soria
B
B
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