HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 289/5/E900    most recent 00101.2005v1 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 Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (7) Citing Articles via Google Scholar Google Scholar Articles by Taylor, J. T. Articles by Li, M. Search for Related Content PubMed PubMed Citation Articles by Taylor, J. T. Articles by Li, M.

Role of high-voltage-activated calcium channels in glucose-regulated -cell calcium homeostasis and insulin release

¹Department of Pharmacology, Tulane University Health Sciences Center, New Orleans, Louisiana; and ²Department of Pharmacology, University of South Alabama College of Medicine, Mobile, Alabama

Submitted 8 March 2005 ; accepted in final form 2 June 2005

High-voltage-activated (HVA) calcium channels are known to be the primary source of calcium for glucose-stimulated insulin secretion. However, few studies have investigated how these channels can be regulated by chronically elevated levels of glucose. In the present study, we determined the level of expression of the four major HVA calcium channels (N-type, P/Q-type, L_C-type, and L_D-type) in rat pancreatic -cells. Using quantitative real-time PCR (QRT-PCR), we found the expression of all four HVA genes in rat insulinoma cells (INS-1) and in primary isolated rat islet cells. We then determined the role of each channel in insulin secretion by using channel-selective antagonists. Insulin secretion analysis revealed that N- and L-type channels are both involved in immediate glucose-induced insulin secretion. However, L-type was preferentially coupled to secretion at later time points. P/Q-type channels were not found to play a role in insulin secretion at any stage. It was also found that long-term exposure to elevated glucose increases basal calcium in these cells. Interestingly, chronically elevated glucose decreased the mRNA expression of the channels involved with insulin secretion and diminished the level of stimulated calcium influx in these cells. Using whole cell patch clamp, we found that N- and L-type channel currents increase gradually subsequent to lower intracellular calcium perfusion, suggesting that these channels may be regulated by glucose-induced changes in calcium.

glucose desensitization; insulinoma cells; diabetes

This article has been cited by other articles:

				M. Hiriart and L. Aguilar-Bryan Channel regulation of glucose sensing in the pancreatic {beta}-cell Am J Physiol Endocrinol Metab, December 1, 2008; 295(6): E1298 - E1306. [Abstract] [Full Text] [PDF]

				M. D. Nitert, C. L F Nagorny, A. Wendt, L. Eliasson, and H. Mulder CaV1.2 rather than CaV1.3 is coupled to glucose-stimulated insulin secretion in INS-1 832/13 cells J. Mol. Endocrinol., July 1, 2008; 41(1): 1 - 11. [Abstract] [Full Text] [PDF]

				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]