Long-term exposure to genistein improves insulin secretory function of pancreatic beta-cells.
We recently found that genistein, a plant-derived natural compound, is a novel cAMP signaling agonist in pancreatic beta-cells. In the present study, we further show that exposure of clonal insulin secreting (INS-1E) cells to genistein for 48 h enhanced glucose-stimulated insulin secretion (GSIS), whereas insulin content was not altered, suggesting that genistein-enhanced GSIS is not due to a modulation of insulin synthesis. This genistein effect is protein tyrosine kinase- and K(ATP) channel-independent. In addition, genistein had no effect on glucose transporter-2 expression or cellular ATP production, but similarly augmented pyruvate-stimulated insulin secretion in INS-1E cells, indicating that the improvement of insulin secretory function by long-term genistein exposure is not related to an alternation in glucose uptake or the glycolytic pathway. The enhanced insulin secretion by genistein was associated with elevated intracellular Ca(2+) concentration and dependent on protein kinase A and new protein synthesis as this effect was completely blocked by N-[2-(p-Bromocinnamylamino)ethyl]-5-isoquinolinesulfonamide or cycloheximide. Similarly, 48 h of genistein exposure also enhanced GSIS in freshly isolated mouse and human pancreatic islets, suggesting a non-species-specific and biologically relevant effect. These findings provide evidence that genistein may be a novel bioactive compound that has an anti-diabetic effect by improving insulin secretion from pancreatic beta-cells.
Fu
Zhuo
Z
Department of Human Nutrition, Foods and Exercise, College of Agriculture and Life Sciences, Virginia Polytechnic Institute and State University, Blacksburg, Virginia 24061, USA.
Liu
Dongmin
D
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D002999:Clone Cells; D000242:Cyclic AMP / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D019833:Genistein / Q000494:pharmacology*; D005947:Glucose / Q000494:pharmacology; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D042541:Intracellular Space / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D014176:Protein Biosynthesis / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors
D007328:Insulin; D019833:Genistein; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D005947:Glucose; D002118:Calcium