Diabetes, Vol 45, Issue 12 1766-1773, Copyright © 1996 by American Diabetes Association

ARTICLES

The betaHC-9 pancreatic beta-cell line preserves the characteristics of progenitor mouse islets

M Noda, M Komatsu and GW Sharp
Department of Pharmacology, College of Veterinary Medicine, Cornell University, Ithaca, New York, USA.

betaHC-9 is a pancreatic beta-cell line that is derived from the hyperplastic islets of transgenic mice that express the simian virus 40 tumor antigen gene in the islets. This cell secretes insulin in response to glucose in a concentration-dependent manner. Maximal and half-maximal concentrations were approximately 20 and approximately 10 mmol/l, respectively, with a maximal fractional release that averaged 3.7% of the total cellular insulin content per 60 min. The cellular insulin content was 3-9% of the content of mouse islet cells. Under perifusion conditions, high glucose concentrations induced a sharp first phase that lasted approximately 10 min and a succeeding second phase of sustained release, as exhibited by mouse islets. The cells did not show a rising second phase as seen with rat islets. This biphasic response was obtained without the need for activators of protein kinase A such as forskolin or 3-isobutyl-1-methylxanthine. The dose-dependency and the phasic response to glucose were essentially invariable up to passage 38 but thereafter declined. The cells respond to various well-known stimulators of insulin secretion, including leucine and arginine; to modulators such as carbachol, glucagon-like peptide I, and pituitary adenylyl cyclase activating polypeptide; and to the inhibitors norepinephrine, somatostatin, and galanin. The pharmacological agents glibenclamide, 12-O-tetradecanoylphorbol-13-acetate, and KCl stimulate and forskolin potentiates insulin release. Mannoheptulose, 2-deoxyglucose, and nitrendipine inhibit glucose-stimulated insulin release from the cells. The intracellular Ca2+ concentration was raised by high glucose and by glibenclamide. In conclusion, this cell line preserves the fundamental characteristics of the progenitor normal mouse islets very well. Although several cell lines have been reported to have glucose-responsive insulin secretion, few demonstrate clear biphasic secretion as this cell line displays. In this context, this cell line should serve as a potent tool for studying the mechanisms of insulin secretion, especially the important phasic secretion.
CiteULike    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				G.-H. Sun-Wada, T. Toyomura, Y. Murata, A. Yamamoto, M. Futai, and Y. Wada The a3 isoform of V-ATPase regulates insulin secretion from pancreatic {beta}-cells J. Cell Sci., November 1, 2006; 119(21): 4531 - 4540. [Abstract] [Full Text] [PDF]

				M. Noda, S. Yamashita, N. Takahashi, K. Eto, L.-M. Shen, K. Izumi, S. Daniel, Y. Tsubamoto, T. Nemoto, M. Iino, et al. Switch to Anaerobic Glucose Metabolism with NADH Accumulation in the beta -Cell Model of Mitochondrial Diabetes. CHARACTERISTICS OF beta HC9 CELLS DEFICIENT IN MITOCHONDRIAL DNA TRANSCRIPTION J. Biol. Chem., October 25, 2002; 277(44): 41817 - 41826. [Abstract] [Full Text] [PDF]

				R. A. Waterland and C. Garza Early Postnatal Nutrition Determines Adult Pancreatic Glucose-Responsive Insulin Secretion and Islet Gene Expression in Rats J. Nutr., March 1, 2002; 132(3): 357 - 364. [Abstract] [Full Text] [PDF]

				T. K. Bratanova-Tochkova, H. Cheng, S. Daniel, S. Gunawardana, Y.-J. Liu, J. Mulvaney-Musa, T. Schermerhorn, S. G. Straub, H. Yajima, and G. W.G. Sharp Triggering and Augmentation Mechanisms, Granule Pools, and Biphasic Insulin Secretion Diabetes, February 1, 2002; 51(90001): S83 - 90. [Abstract] [Full Text] [PDF]

				K. Eto, T. Yamashita, Y. Tsubamoto, Y. Terauchi, K. Hirose, N. Kubota, S. Yamashita, J. Taka, S. Satoh, H. Sekihara, et al. Phosphatidylinositol 3-Kinase Suppresses Glucose-Stimulated Insulin Secretion by Affecting Post-Cytosolic [Ca2+] Elevation Signals Diabetes, January 1, 2002; 51(1): 87 - 97. [Abstract] [Full Text] [PDF]

				K. Sooy, T. Schermerhorn, M. Noda, M. Surana, W. B. Rhoten, M. Meyer, N. Fleischer, G. W. G. Sharp, and S. Christakos Calbindin-D28k Controls [Ca2+]i and Insulin Release. EVIDENCE OBTAINED FROM CALBINDIN-D28k KNOCKOUT MICE AND beta CELL LINES J. Biol. Chem., November 26, 1999; 274(48): 34343 - 34349. [Abstract] [Full Text] [PDF]

				K. K. Papas and M. A. C. Jarema Glucose-stimulated insulin secretion is not obligatorily linked to an increase in O2 consumption in beta HC9 cells Am J Physiol Endocrinol Metab, December 1, 1998; 275(6): E1100 - E1106. [Abstract] [Full Text] [PDF]

				T. Hayakawa, M. Noda, K. Yasuda, H. Yorifuji, S. Taniguchi, I. Miwa, H. Sakura, Y. Terauchi, J.-i. Hayashi, G. W. G. Sharp, et al. Ethidium Bromide-induced Inhibition of Mitochondrial Gene Transcription Suppresses Glucose-stimulated Insulin Release in the Mouse Pancreatic beta -Cell Line beta HC9 J. Biol. Chem., August 7, 1998; 273(32): 20300 - 20307. [Abstract] [Full Text] [PDF]

				S. G. Straub, B. Kornreich, R. E. Oswald, E. F. Nemeth, and G. W. G. Sharp The Calcimimetic R-467 Potentiates Insulin Secretion in Pancreatic beta Cells by Activation of a Nonspecific Cation Channel J. Biol. Chem., June 16, 2000; 275(25): 18777 - 18784. [Abstract] [Full Text] [PDF]

				Y. Tsubamoto, K. Eto, M. Noda, S. Daniel, S. Suga, S. Yamashita, H. Kasai, M. Wakui, G. W. G. Sharp, S. Kimura, et al. Hexamminecobalt(III) Chloride Inhibits Glucose-induced Insulin Secretion at the Exocytotic Process J. Biol. Chem., January 26, 2001; 276(5): 2979 - 2985. [Abstract] [Full Text] [PDF]