Endocrinology, Vol 126, 1750-1755, Copyright © 1990 by Endocrine Society

ARTICLES

Effect of glucagon or somatostatin on desensitized insulin secretion

JL Bolaffi, G Rodd, YH Ma and GM Grodsky
Metabolic Research Unit, University of California, San Francisco 94143.

In this study we have examined the role of glucagon and somatostatin in regulating glucose-induced desensitization of insulin secretion from rat islets. Measured in batch incubations with medium routinely used to induce three phases of insulin secretion, secreted glucagon levels fell off over 24 h to 20% of peak secretion levels. Although more responsive to various secretagogues, somatostatin secretion also declined to the same degree. Thus, the A- and D-cells desensitize to chronic stimulation as does the B cell. In other experiments, added glucagon (10(-6) M) enhanced glucose (11 X 10(-3) M)-stimulated insulin secretion 34% in the first 3 h; however, islets became insensitive to continuous glucagon by 4 h. The exogenous glucagon did not prevent or delay glucose-induced desensitization of insulin secretion. When glucagon was administered as acute 1-h tests over continuous glucose administration, the degree of B-cell response did not differ in the 1st, 3rd, or 6th hours and appeared to increase in the 21st hour. When islets were perifused continuously with glucose (22 X 10(-3) M) plus 3 X 10(-7) M somatostatin, glucose-induced insulin secretion was suppressed 50% in the first 3 h, but this inhibitory effect disappeared after 6 h. Desensitization was slightly delayed, but not prevented. When somatostatin was administered as acute 1-h tests over continuous glucose perifusion, the B-cell response was relatively constant in the 3rd, 6th, and 21st hours. Results show that 1) islet release of glucagon and somatostatin desensitizes during constant stimulation; and 2) islet release of insulin desensitizes to chronic potentiation or inhibition, respectively, by these hormones. Furthermore, 3) changing B- cell sensitivity to either glucagon or somatostatin cannot account for observed desensitization of insulin secretion with chronic glucose exposure.

This article has been cited by other articles:

				J. Gromada, I. Franklin, and C. B. Wollheim {alpha}-Cells of the Endocrine Pancreas: 35 Years of Research but the Enigma Remains Endocr. Rev., February 1, 2007; 28(1): 84 - 116. [Abstract] [Full Text] [PDF]

				P. Han, J. Werber, M. Surana, N. Fleischer, and T. Michaeli The Calcium/Calmodulin-dependent Phosphodiesterase PDE1C Down-regulates Glucose-induced Insulin Secretion J. Biol. Chem., August 6, 1999; 274(32): 22337 - 22344. [Abstract] [Full Text] [PDF]