Diabetes, Vol 48, Issue 5 997-1005, Copyright © 1999 by American Diabetes Association

ARTICLES

Beta-cell hypertrophy in fa/fa rats is associated with basal glucose hypersensitivity and reduced SNARE protein expression

CB Chan, RM MacPhail, L Sheu, MB Wheeler and HY Gaisano
Department of Anatomy and Physiology, Atlantic Veterinary College, University of Prince Edward Island, Charlottetown, Canada. cchan@upei.ca

In normal isolated beta-cells, the response to glucose is heterogeneous and characterized by an increasing number of secretory cells as glucose concentration rises (Pipeleers DG, Kiekens R, Ling Z, Wilikens A, Schuit F: Physiologic relevance of heterogeneity in the pancreatic beta-cell population. Diabetologia 37 (Suppl. 2):S57-S64, 1994). We hypothesized that fasting hyperinsulinemia in obesity might be explained by altered beta-cell heterogeneity of signal transduction mechanisms, possibly involving exocytotic proteins. Insulin secretion from individual beta-cells sorted according to the size of the islet donor (<125 microm, >250 microm, and intermediate diameter) was measured by reverse hemolytic plaque assay. Beta-cells from fa/fa rats were hypertrophied 25-40%, independent of donor islet size. This was accompanied by an increased proportion of secretory cells (recruitment) at 5.5-11.0 mmol/l glucose, increased secretion per cell at 2.8 mmol/l glucose, and decreased insulin content after acute glucose exposure without an increase in secretion per cell. Decreased expression of exocytotic (soluble N-ethylmaleimide-sensitive fusion protein receptor [SNARE]) proteins, vesicle-associated membrane protein isoform 2 (VAMP-2), synaptosomal protein of 25 kDa (SNAP-25), and syntaxin-1 and -2 in fa/fa beta-cells may contribute to the failure to sustain excessive plaque size at higher glucose concentrations. Fasting hyperinsulinemia may be maintained by increased recruitment and an exaggerated secretory response in all fa-derived islet populations. Glucose regulates beta-cell responsiveness in the short term, and these effects may involve altered expression of SNARE proteins.
CiteULike    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				E. Oh, C. J. Heise, J. M. English, M. H. Cobb, and D. C. Thurmond WNK1 Is a Novel Regulator of Munc18c-Syntaxin 4 Complex Formation in Soluble NSF Attachment Protein Receptor (SNARE)-mediated Vesicle Exocytosis J. Biol. Chem., November 9, 2007; 282(45): 32613 - 32622. [Abstract] [Full Text] [PDF]

				Y. M. Leung, E. P. Kwan, B. Ng, Y. Kang, and H. Y. Gaisano SNAREing Voltage-Gated K+ and ATP-Sensitive K+ Channels: Tuning {beta}-Cell Excitability with Syntaxin-1A and Other Exocytotic Proteins Endocr. Rev., October 1, 2007; 28(6): 653 - 663. [Abstract] [Full Text] [PDF]

				B. Ng, Y. Kang, C. L. Elias, Y. He, H. Xie, J. B. Hansen, P. Wahl, and H. Y. Gaisano The Actions of a Novel Potent Islet {beta}-Cell Specific ATP-Sensitive K+ Channel Opener Can Be Modulated by Syntaxin-1A Acting on Sulfonylurea Receptor 1 Diabetes, August 1, 2007; 56(8): 2124 - 2134. [Abstract] [Full Text] [PDF]

				B. Ke, E. Oh, and D. C. Thurmond Doc2beta Is a Novel Munc18c-interacting Partner and Positive Effector of Syntaxin 4-mediated Exocytosis J. Biol. Chem., July 27, 2007; 282(30): 21786 - 21797. [Abstract] [Full Text] [PDF]

				M. Dubois, P. Vacher, B. Roger, D. Huyghe, B. Vandewalle, J. Kerr-Conte, F. Pattou, N. Moustaid-Moussa, and J. Lang Glucotoxicity Inhibits Late Steps of Insulin Exocytosis Endocrinology, April 1, 2007; 148(4): 1605 - 1614. [Abstract] [Full Text] [PDF]

				L. E. Parton, P. J. McMillen, Y. Shen, E. Docherty, E. Sharpe, F. Diraison, C. P. Briscoe, and G. A. Rutter Limited role for SREBP-1c in defective glucose-induced insulin secretion from Zucker diabetic fatty rat islets: a functional and gene profiling analysis Am J Physiol Endocrinol Metab, November 1, 2006; 291(5): E982 - E994. [Abstract] [Full Text] [PDF]

				T. Wolf-Goldberg, I. Michaelevski, L. Sheu, H. Y. Gaisano, D. Chikvashvili, and I. Lotan Target Soluble N-Ethylmaleimide-Sensitive Factor Attachment Protein Receptors (t-SNAREs) Differently Regulate Activation and Inactivation Gating of Kv2.2 and Kv2.1: Implications on Pancreatic Islet Cell Kv Channels Mol. Pharmacol., September 1, 2006; 70(3): 818 - 828. [Abstract] [Full Text] [PDF]

				C.-G. Ostenson, H. Gaisano, L. Sheu, A. Tibell, and T. Bartfai Impaired Gene and Protein Expression of Exocytotic Soluble N-Ethylmaleimide Attachment Protein Receptor Complex Proteins in Pancreatic Islets of Type 2 Diabetic Patients Diabetes, February 1, 2006; 55(2): 435 - 440. [Abstract] [Full Text] [PDF]

				Y. M. Leung, I. Ahmed, L. Sheu, R. G. Tsushima, N. E. Diamant, M. Hara, and H. Y. Gaisano Electrophysiological Characterization of Pancreatic Islet Cells in the Mouse Insulin Promoter-Green Fluorescent Protein Mouse Endocrinology, November 1, 2005; 146(11): 4766 - 4775. [Abstract] [Full Text] [PDF]

				R. McGirr, C. E. Ejbick, D. E. Carter, J. D. Andrews, Y. Nie, T. C. Friedman, and S. Dhanvantari Glucose Dependence of the Regulated Secretory Pathway in {alpha}TC1-6 Cells Endocrinology, October 1, 2005; 146(10): 4514 - 4523. [Abstract] [Full Text] [PDF]

				P. P.L. Lam, Y.-M. Leung, L. Sheu, J. Ellis, R. G. Tsushima, L. R. Osborne, and H. Y. Gaisano Transgenic Mouse Overexpressing Syntaxin-1A as a Diabetes Model Diabetes, September 1, 2005; 54(9): 2744 - 2754. [Abstract] [Full Text] [PDF]

				T. Saito, S. Okada, E. Yamada, K. Ohshima, H. Shimizu, K. Shimomura, M. Sato, J. E. Pessin, and M. Mori Syntaxin 4 and Synip (Syntaxin 4 Interacting Protein) Regulate Insulin Secretion in the Pancreatic {beta} HC-9 Cell J. Biol. Chem., September 19, 2003; 278(38): 36718 - 36725. [Abstract] [Full Text] [PDF]

				L. Sheu, E. A. Pasyk, J. Ji, X. Huang, X. Gao, F. Varoqueaux, N. Brose, and H. Y. Gaisano Regulation of Insulin Exocytosis by Munc13-1 J. Biol. Chem., July 18, 2003; 278(30): 27556 - 27563. [Abstract] [Full Text] [PDF]

				H. Y. Gaisano, C.-G. Ostenson, L. Sheu, M. B. Wheeler, and S. Efendic Abnormal Expression of Pancreatic Islet Exocytotic Soluble N-Ethylmaleimide-Sensitive Factor Attachment Protein Receptors in Goto-Kakizaki Rats Is Partially Restored by Phlorizin Treatment and Accentuated by High Glucose Treatment Endocrinology, November 1, 2002; 143(11): 4218 - 4226. [Abstract] [Full Text] [PDF]

				P. E. MacDonald, G. Wang, S. Tsuk, C. Dodo, Y. Kang, L. Tang, M. B. Wheeler, M. S. Cattral, J. R. T. Lakey, A. M. F. Salapatek, et al. Synaptosome-Associated Protein of 25 Kilodaltons Modulates Kv2.1 Voltage-Dependent K+ Channels in Neuroendocrine Islet {beta}-Cells through an Interaction with the Channel N Terminus Mol. Endocrinol., November 1, 2002; 16(11): 2452 - 2461. [Abstract] [Full Text] [PDF]

				J. Ji, S.-N. Yang, X. Huang, X. Li, L. Sheu, N. Diamant, P.-O. Berggren, and H. Y. Gaisano Modulation of L-Type Ca2+ Channels by Distinct Domains Within SNAP-25 Diabetes, May 1, 2002; 51(5): 1425 - 1436. [Abstract] [Full Text] [PDF]

				A. K. Busch, D. Cordery, G. S. Denyer, and T. J. Biden Expression Profiling of Palmitate- and Oleate-Regulated Genes Provides Novel Insights Into the Effects of Chronic Lipid Exposure on Pancreatic {beta}-Cell Function Diabetes, April 1, 2002; 51(4): 977 - 987. [Abstract] [Full Text] [PDF]

				X. Huang, Y.-H. Kang, E. A. Pasyk, L. Sheu, M. B. Wheeler, W. S. Trimble, A. Salapatek, and H. Y. Gaisano Ca2+ influx and cAMP elevation overcame botulinum toxin A but not tetanus toxin inhibition of insulin exocytosis Am J Physiol Cell Physiol, September 1, 2001; 281(3): C740 - C750. [Abstract] [Full Text] [PDF]

				M. Srinivasan, R. Aalinkeel, F. Song, B. Lee, S. G. Laychock, and M. S. Patel Adaptive changes in insulin secretion by islets from neonatal rats raised on a high-carbohydrate formula Am J Physiol Endocrinol Metab, December 1, 2000; 279(6): E1347 - E1357. [Abstract] [Full Text] [PDF]