Diabetes, Vol 41, Issue 7 861-865, Copyright © 1992 by American Diabetes Association

ARTICLES

Impaired glucose sensitivity of ATP-sensitive K+ channels in pancreatic beta-cells in streptozotocin-induced NIDDM rats

Y Tsuura, H Ishida, Y Okamoto, K Tsuji, T Kurose, M Horie, H Imura, Y Okada and Y Seino
Department of Metabolism and Clinical Nutrition, Kyoto University Faculty of Medicine, Japan.

ATP-sensitive K+ channels (KATP channels) are known to play a key role in the cellular mechanism of insulin secretion from pancreatic beta cells. In order to examine the possible impairment of KATP channel function in non-insulin-dependent diabetes mellitus (NIDDM), we have studied the properties of the KATP channels in single beta cells of neonatally streptozotocin-induced diabetic rats (NSZ rats) using the patch-clamp technique. The unitary conductance of the channel in diabetic beta-cells was virtually identical to that in control beta cells and there was no difference in the sensitivity to ATP and glibenclamide of KATP channels between the NIDDM and control groups. In response to glucose, the activity of the KATP channels was diminished in a dose-dependent manner in both control and diabetic cells. However, the inhibition of the KATP channels in beta-cells of NSZ rats was significantly less than that in control cells. Even in the presence of 11.1 mM glucose, the openings of a few single KATP channels were consistently observed in cell-attached patch membranes of diabetic, but not control, beta-cells. Thus, it appears that the impaired insulinotropic action of glucose in beta-cells in NSZ rats is associated with a reduced sensitivity of the KATP channel to glucose, but not to ATP, presumably due to a deficiency in glucose metabolism.
CiteULike    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				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]

				N. M. Doliba, W. Qin, M. Z. Vatamaniuk, C. Li, D. Zelent, H. Najafi, C. W. Buettger, H. W. Collins, R. D. Carr, M. A. Magnuson, et al. Restitution of defective glucose-stimulated insulin release of sulfonylurea type 1 receptor knockout mice by acetylcholine Am J Physiol Endocrinol Metab, May 1, 2004; 286(5): E834 - E843. [Abstract] [Full Text] [PDF]

				N. M. Doliba, M. Z. Vatamaniuk, C. W. Buettger, W. Qin, H. W. Collins, S. L. Wehrli, R. D. Carr, and F. M. Matschinsky Differential Effects of Glucose and Glyburide on Energetics and Na+ Levels of {beta}HC9 Cells: Nuclear Magnetic Resonance Spectroscopy and Respirometry Studies Diabetes, February 1, 2003; 52(2): 394 - 402. [Abstract] [Full Text] [PDF]

				C. G. Sobey Potassium Channel Function in Vascular Disease Arterioscler. Thromb. Vasc. Biol., January 1, 2001; 21(1): 28 - 38. [Abstract] [Full Text] [PDF]

				E. Mukai, H. Ishida, S. Kato, Y. Tsuura, S. Fujimoto, A. Ishida-Takahashi, M. Horie, K. Tsuda, and Y. Seino Metabolic inhibition impairs ATP-sensitive K+ channel block by sulfonylurea in pancreatic beta -cells Am J Physiol Endocrinol Metab, January 1, 1998; 274(1): E38 - E44. [Abstract] [Full Text] [PDF]

				T. J. Ribar, C.-R. Jan, G. J. Augustine, and A. R. Means Defective Glycolysis and Calcium Signaling Underlie Impaired Insulin Secretion in a Transgenic Mouse J. Biol. Chem., December 1, 1995; 270(48): 28688 - 28695. [Abstract] [Full Text] [PDF]

				N. Inagaki, Y. Tsuura, N. Namba, K. Masuda, T. Gonoi, M. Horie, Y. Seino, M. Mizuta, and S. Seino Cloning and Functional Characterization of a Novel ATP-sensitive Potassium Channel Ubiquitously Expressed in Rat Tissues, including Pancreatic Islets, Pituitary, Skeletal Muscle, and Heart J. Biol. Chem., March 17, 1995; 270(11): 5691 - 5694. [Abstract] [Full Text] [PDF]