AJP - Cell Physiology, Vol 264, Issue 6 C1458-C1465, Copyright © 1993 by American Physiological Society

ARTICLES

K+ channel and alpha 2-adrenergic effects on glucose-induced Ca2+i surges: aberrant behavior in ob/ob mice

L. Fournier, J. F. Whitfield, H. Xiang, J. L. Schwartz and N. Begin-Heick
Department of Biochemistry, University of Ottawa, Ontario, Canada.

Glucose-induced shifts in intracellular free Ca2+ concentration ([Ca2+]i) were quantitatively and temporally the same in ob/ob and +/+ beta-cells. In both, epinephrine promptly and protractedly inhibited the glucose-induced [Ca2+]i surge via a pertussis toxin-sensitive alpha 2-adrenergic mechanism that was reversible by potassium depolarization. When added before glucose, epinephrine blocked completely in the ob/ob beta-cells, but in the +/+ beta-cells it produced a delayed, reduced, and transient intracellular Ca2+ (Ca2+i) surge. Neither the ATP-sensitive K+ channel blocker tolbutamide nor the large-conductance Ca(2+)-activated K+ channel (Kmaxi) blocker charybdotoxin reversed the effect of epinephrine. Tetraethylammonium (TEA), a blocker of both the Kmaxi and the delayed-rectifier K+ channel, and forskolin attenuated the effect of epinephrine in +/+ but not in the ob/ob beta-cells. The data show that 1) alpha 2-adrenoreceptor activation decreases the glucose-stimulated Ca2+i surge in +/+ beta-cells primarily by activating a tolbutamide- and charybdotoxin-insensitive, TEA- and forskolin-sensitive K+ channel; 2) the hypersecretion of insulin in ob/ob beta-cells is not due to enhanced glucose-induced Ca2+ influx; and 3) the ob/ob beta-cells are aberrant with regard to alpha 2-adrenergic modulation.

This article has been cited by other articles:

				P. E. MacDonald, W. El-kholy, M. J. Riedel, A. M. F. Salapatek, P. E. Light, and M. B. Wheeler The Multiple Actions of GLP-1 on the Process of Glucose-Stimulated Insulin Secretion Diabetes, December 1, 2002; 51(90003): S434 - 442. [Abstract] [Full Text] [PDF]

				J. Tateishi and J. E. Faber ATP-Sensitive K+ Channels Mediate {alpha}2D-Adrenergic Receptor Contraction of Arteriolar Smooth Muscle and Reversal of Contraction by Hypoxia Circ. Res., January 1, 1995; 76(1): 53 - 63. [Abstract] [Full Text]