We examined the effects of phosphatidylinositol 3-kinase (PI3K) inhibition by wortmannin or LY294002 on glucose-induced secretion from mouse islets. Islets were collagenase isolated and perifused or subjected to Western blot analyses and probed for insulin receptor-signaling components. In agreement with previous studies, mouse islets, when compared with rat islets, were minimally responsive to 10 mM glucose stimulation. The inclusion of 50 nM wortmannin or 10 microM LY294002 significantly amplified 10 mM glucose-induced release from mouse islets. The effect of wortmannin was abolished by the calcium channel antagonist nitrendipine or by lowering the glucose level to 3 mM. Wortmannin had no effect on 10 mM alpha-ketoisocaproate-induced secretion. In contrast to its potentiating effect on islets from CD-1 mice, wortmannin had no effect on 10 mM glucose-induced release from ob/ob mouse islets. Western blot analyses revealed the presence of the insulin receptor, insulin receptor substrate proteins 1 and 2 and PI3K in CD-1 islets. These results support the concept that a PI3K-dependent signaling pathway exists in beta-cells and that it may function to restrain glucose-induced insulin secretion from beta-cells. They also suggest that, as insulin resistance develops in peripheral tissues, a potential result of impaired PI3K activation, the same biochemical anomaly in beta-cells promotes a linked increase in insulin secretion to maintain glucose homeostasis.

This article has been cited by other articles:

				G. M. Pigeau, J. Kolic, B. J. Ball, M. B. Hoppa, Y. W. Wang, T. Ruckle, M. Woo, J. E. Manning Fox, and P. E. MacDonald Insulin Granule Recruitment and Exocytosis Is Dependent on p110{gamma} in Insulinoma and Human {beta}-Cells Diabetes, September 1, 2009; 58(9): 2084 - 2092. [Abstract] [Full Text] [PDF]

				A. Nishida, A. Andoh, O. Inatomi, and Y. Fujiyama Interleukin-32 Expression in the Pancreas J. Biol. Chem., June 26, 2009; 284(26): 17868 - 17876. [Abstract] [Full Text] [PDF]

				A. Assmann, K. Ueki, J. N. Winnay, T. Kadowaki, and R. N. Kulkarni Glucose Effects on Beta-Cell Growth and Survival Require Activation of Insulin Receptors and Insulin Receptor Substrate 2 Mol. Cell. Biol., June 1, 2009; 29(11): 3219 - 3228. [Abstract] [Full Text] [PDF]

				A. Nishida, A. Andoh, M. Shioya, S. Kim-Mitsuyama, A. Takayanagi, and Y. Fujiyama Phosphatidylinositol 3-kinase/Akt signaling mediates interleukin-32{alpha} induction in human pancreatic periacinar myofibroblasts Am J Physiol Gastrointest Liver Physiol, March 1, 2008; 294(3): G831 - G838. [Abstract] [Full Text] [PDF]

				E. A. Bradley, M. G. Clark, and S. Rattigan Acute effects of wortmannin on insulin's hemodynamic and metabolic actions in vivo Am J Physiol Endocrinol Metab, March 1, 2007; 292(3): E779 - E787. [Abstract] [Full Text] [PDF]

				H. Cheng, S. G. Straub, and G. W. G. Sharp Inhibitory role of Src family tyrosine kinases on Ca2+-dependent insulin release Am J Physiol Endocrinol Metab, March 1, 2007; 292(3): E845 - E852. [Abstract] [Full Text] [PDF]

				A. I. Tarasov, C. A.J. Girard, and F. M. Ashcroft ATP Sensitivity of the ATP-Sensitive K+ Channel in Intact and Permeabilized Pancreatic {beta}-Cells Diabetes, September 1, 2006; 55(9): 2446 - 2454. [Abstract] [Full Text] [PDF]

				Y. W. Chen, C. F. Huang, K. S. Tsai, R. S. Yang, C. C. Yen, C. Y. Yang, S. Y. Lin-Shiau, and S. H. Liu The Role of Phosphoinositide 3-Kinase/Akt Signaling in Low-Dose Mercury-Induced Mouse Pancreatic {beta}-Cell Dysfunction In Vitro and In Vivo Diabetes, June 1, 2006; 55(6): 1614 - 1624. [Abstract] [Full Text] [PDF]

				W S Zawalich, H Yamazaki, K C Zawalich, and G Cline Comparative effects of amino acids and glucose on insulin secretion from isolated rat or mouse islets J. Endocrinol., November 1, 2004; 183(2): 309 - 319. [Abstract] [Full Text] [PDF]

				P. A. Ortiz, N. J. Hong, and J. L. Garvin Luminal flow induces eNOS activation and translocation in the rat thick ascending limb. II. Role of PI3-kinase and Hsp90 Am J Physiol Renal Physiol, August 1, 2004; 287(2): F281 - F288. [Abstract] [Full Text] [PDF]

				E. Chernogubova, B. Cannon, and T. Bengtsson Norepinephrine Increases Glucose Transport in Brown Adipocytes via {beta}3-Adrenoceptors through a cAMP, PKA, and PI3-Kinase-Dependent Pathway Stimulating Conventional and Novel PKCs Endocrinology, January 1, 2004; 145(1): 269 - 280. [Abstract] [Full Text] [PDF]

				S. Srivastava and H. J. Goren Insulin Constitutively Secreted by {beta}-Cells Is Necessary for Glucose-Stimulated Insulin Secretion Diabetes, August 1, 2003; 52(8): 2049 - 2056. [Abstract] [Full Text] [PDF]