This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Yamada, S. Articles by Hashizume, K. Search for Related Content PubMed PubMed Citation Articles by Yamada, S. Articles by Hashizume, K.

Time-Dependent Stimulation of Insulin Exocytosis by 3',5'-Cyclic Adenosine Monophosphate in the Rat Islet ß-Cell

Department of Cell Biology, Institute for Molecular and Cellular Regulation, Gunma University (S.Y., I.K.), Maebashi, 371-8512, Japan; and Department of Aging Medicine and Geriatrics, School of Medicine (M.K., Y.S., K.Y., K.H.), and Center for Health Services (T.A.), Shinshu University, Matsumoto 390-8621, Japan

Address all correspondence and requests for reprints to: Dr. Toru Aizawa, Center for Health Services, Shinshu University, 3-1-1 Asahi, Matsumoto 390-8621, Japan. E-mail: traizawa{at}hsp.md.shinshu-u.ac.jp.

Isolated rat islets were exposed to cAMP-elevating agents and/or nutrients. Insulin exocytosis subsequently triggered by a depolarizing concentration of K⁺ or a stimulatory concentration of glucose was employed as an index of time-dependent potentiation (TDP). Stimulatory concentrations (5.5 mM) of glucose caused TDP, and 6 µM forskolin (an activator of adenylyl cyclase) significantly enhanced it (3.1-fold at most). Forskolin produced an 8.0-fold increase in islet cell cAMP; however, it returned to the baseline after washout by the time of stimulation of exocytosis. Two millimoles of dibutyryl cAMP (a cAMP analog), 0.1 mM isobutylmethylxanthine (a phosphodiesterase inhibitor), and 100 nM glucagon-like peptide-1 (an incretin hormone) also enhanced glucoseinduced TDP. The time-dependent effect of cAMP was not attenuated by protein kinase A inhibitors (200 µM adenosine 3',5'-cyclic monophosphothioate, Rp isomer, and 10 µM H89). Although glucose-induced TDP was attenuated by NaN₃ (a mitochondrial poison) and cerulenin (an inhibitor of protein acylation), cAMP enhancement of it was unaffected by these agents. In conclusion, cAMP time-dependently stimulates insulin exocytosis, provided the extracellular glucose concentration is equivalent to or higher than ambient plasma levels. Protein kinase A, mitochondrial metabolism, and protein acylation are not involved in this cAMP action. Incretin stimulation of insulin exocytosis may occur in part via this mechanism.

This article has been cited by other articles:

				L. Zhou, X. Wang, L. Shao, Y. Yang, W. Shang, G. Yuan, B. Jiang, F. Li, J. Tang, H. Jing, et al. Berberine Acutely Inhibits Insulin Secretion from {beta}-Cells through 3',5'-Cyclic Adenosine 5'-Monophosphate Signaling Pathway Endocrinology, September 1, 2008; 149(9): 4510 - 4518. [Abstract] [Full Text] [PDF]

				Y. Suzuki, H. Zhang, N. Saito, I. Kojima, T. Urano, and H. Mogami Glucagon-like Peptide 1 Activates Protein Kinase C through Ca2+-dependent Activation of Phospholipase C in Insulin-secreting Cells J. Biol. Chem., September 29, 2006; 281(39): 28499 - 28507. [Abstract] [Full Text] [PDF]

				D. Liu, W. Zhen, Z. Yang, J. D. Carter, H. Si, and K. A. Reynolds Genistein Acutely Stimulates Insulin Secretion in Pancreatic {beta}-Cells Through a cAMP-Dependent Protein Kinase Pathway. Diabetes, April 1, 2006; 55(4): 1043 - 1050. [Abstract] [Full Text] [PDF]

				H. Zhang, M. Nagasawa, S. Yamada, H. Mogami, Y. Suzuki, and I. Kojima Bimodal role of conventional protein kinase C in insulin secretion from rat pancreatic {beta} cells J. Physiol., November 15, 2004; 561(1): 133 - 147. [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]