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 Wang, L. Articles by Li, M. Search for Related Content PubMed PubMed Citation Articles by Wang, L. Articles by Li, M.

A Low Voltage-Activated Ca²⁺ Current Mediates Cytokine-Induced Pancreatic ß-Cell Death¹

Departments of Pharmacology (L.W., A.B., F.H., M.L.) and Biochemistry (Z.Z., R.E.H.), University of South Alabama College of Medicine, Mobile, Alabama 36688; and The Rolf Luft Center for Diabetes Research, Department of Molecular Medicine, Karolinska Institute (P.-O.B.), S-171 76 Stockholm, Sweden

Address all correspondence and requests for reprints to: Ming Li, Ph.D., Department of Pharmacology, University of South Alabama College of Medicine, Mobile, Alabama 36688. E-mail: mli{at}jaguar1.usouthal.edu

Insulin-dependent diabetes mellitus is characterized by the selective destruction of pancreatic ß-cells. Chronic treatment with cytokines induced a low voltage-activated (LVA) Ca²⁺ current in mouse ß-cells. The concomitant increase in the basal cytoplasmic free Ca²⁺ concentration ([Ca²⁺]_i) was associated with DNA fragmentation and cell death. Antagonists of LVA Ca²⁺ channels prevented this elevation of basal [Ca²⁺]_i and DNA fragmentation and reduced the percentage of cell death. Exposure to cytokines did not affect the profile of Ca²⁺ currents or basal [Ca²⁺]_i in glucagon-secreting -cells. An increased Ca²⁺ signal through LVA Ca²⁺ channels may thus be a key feature in cytokine-induced ß-cell destruction.

This article has been cited by other articles:

				V. Navarro-Tableros, T. Fiordelisio, A. Hernandez-Cruz, and M. Hiriart Physiological development of insulin secretion, calcium channels, and GLUT2 expression of pancreatic rat beta-cells Am J Physiol Endocrinol Metab, April 1, 2007; 292(4): E1018 - E1029. [Abstract] [Full Text] [PDF]

				S.-N. Yang and P.-O. Berggren The Role of Voltage-Gated Calcium Channels in Pancreatic {beta}-Cell Physiology and Pathophysiology Endocr. Rev., October 1, 2006; 27(6): 621 - 676. [Abstract] [Full Text] [PDF]

				J. Storling, S. V. Zaitsev, I. L. Kapelioukh, A. E. Karlsen, N. Billestrup, P.-O. Berggren, and T. Mandrup-Poulsen Calcium Has a Permissive Role in Interleukin-1{beta}-Induced c-Jun N-Terminal Kinase Activation in Insulin-Secreting Cells Endocrinology, July 1, 2005; 146(7): 3026 - 3036. [Abstract] [Full Text] [PDF]

				S.-N. Yang and P.-O. Berggren {beta}-Cell CaV channel regulation in physiology and pathophysiology Am J Physiol Endocrinol Metab, January 1, 2005; 288(1): E16 - E28. [Abstract] [Full Text] [PDF]

				R. Aikin, D. Maysinger, and L. Rosenberg Cross-Talk between Phosphatidylinositol 3-Kinase/AKT and c-Jun NH2-Terminal Kinase Mediates Survival of Isolated Human Islets Endocrinology, October 1, 2004; 145(10): 4522 - 4531. [Abstract] [Full Text] [PDF]

				I. Chang, N. Cho, S. Kim, J. Y. Kim, E. Kim, J.-E. Woo, J. H. Nam, S. J. Kim, and M.-S. Lee Role of Calcium in Pancreatic Islet Cell Death by IFN-{gamma}/TNF-{alpha} J. Immunol., June 1, 2004; 172(11): 7008 - 7014. [Abstract] [Full Text] [PDF]

				L. Huang, A. Bhattacharjee, J. T. Taylor, M. Zhang, B. M. Keyser, L. Marrero, and M. Li [Ca2+]i regulates trafficking of Cav1.3 ({alpha}1D Ca2+ channel) in insulin-secreting cells Am J Physiol Cell Physiol, February 1, 2004; 286(2): C213 - C221. [Abstract] [Full Text]

				N. Allaman-Pillet, J. Storling, A. Oberson, R. Roduit, S. Negri, C. Sauser, P. Nicod, J. S. Beckmann, D. F. Schorderet, T. Mandrup-Poulsen, et al. Calcium- and Proteasome-dependent Degradation of the JNK Scaffold Protein Islet-brain 1 J. Biol. Chem., December 5, 2003; 278(49): 48720 - 48726. [Abstract] [Full Text] [PDF]

				J.-H. Liu, S. Konig, M. Michel, S. Arnaudeau, J. Fischer-Lougheed, C. R. Bader, and L. Bernheim Acceleration of human myoblast fusion by depolarization: graded Ca2+ signals involved Development, August 1, 2003; 130(15): 3437 - 3446. [Abstract] [Full Text] [PDF]

				E. Perez-Reyes Molecular Physiology of Low-Voltage-Activated T-type Calcium Channels Physiol Rev, January 1, 2003; 83(1): 117 - 161. [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]

				P. Mariot, K. Vanoverberghe, N. Lalevee, M. F. Rossier, and N. Prevarskaya Overexpression of an alpha 1H (Cav3.2) T-type Calcium Channel during Neuroendocrine Differentiation of Human Prostate Cancer Cells J. Biol. Chem., March 22, 2002; 277(13): 10824 - 10833. [Abstract] [Full Text] [PDF]

				A. Rabinovitch, W. L. Suarez-Pinzon, K. Sooy, K. Strynadka, and S. Christakos Expression of Calbindin-D28k in a Pancreatic Islet {beta}-Cell Line Protects against Cytokine-Induced Apoptosis and Necrosis Endocrinology, August 1, 2001; 142(8): 3649 - 3655. [Abstract] [Full Text] [PDF]

				S. Wu, M. Zhang, P. A. Vest, A. Bhattacharjee, L. Liu, and M. Li A Mibefradil Metabolite Is a Potent Intracellular Blocker of L-Type Ca2+ Currents in Pancreatic beta -Cells J. Pharmacol. Exp. Ther., March 1, 2000; 292(3): 939 - 943. [Abstract] [Full Text]

				J. E. McRory, C. M. Santi, K. S. C. Hamming, J. Mezeyova, K. G. Sutton, D. L. Baillie, A. Stea, and T. P. Snutch Molecular and Functional Characterization of a Family of Rat Brain T-type Calcium Channels J. Biol. Chem., February 2, 2001; 276(6): 3999 - 4011. [Abstract] [Full Text] [PDF]