Effect of glucagon or somatostatin on desensitized insulin secretion.
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.
Bolaffi
J L
JL
Metabolic Research Unit, University of California, San Francisco 94143.
Rodd
G
G
Ma
Y H
YH
Grodsky
G M
GM
D000818:Animals; D001402:B-Lymphocytes / Q000187:drug effects; D005576:Colforsin / Q000494:pharmacology; D005934:Glucagon / Q000378:metabolism / Q000494:pharmacology*; D066298:In Vitro Techniques; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D013004:Somatostatin / Q000378:metabolism / Q000494:pharmacology*; D013997:Time Factors
D007328:Insulin; D005576:Colforsin; D013004:Somatostatin; D005934:Glucagon