Functional receptors for the insulinotropic hormone glucagon-like peptide-I(7–37) on a somatostatin secreting cell line

Abstract

Glucagon-like peptide-I (7–37) [(GLP-I(7–37)] is an instestinal peptide hormone that has potent insulinotropic activities in vivo in response to oral nutrients. In the isolated perfused pancreas, and in vitro in cultured B cells, GLP-I(7–37) receptor binding and GLP-I(7–37)-induced cAMP generation and harmone secretion was studied using cell lines producing insulin/B cell (βTC-1), glucagon/A cell (INR1G9) and somatostatin/D cell (RIN 1027-B2). [ 125I]GLP-I(7–37) bound specifically to both B and D cells but not to A cells. GLP-I(7–37) induced cAMP-formation in B and D cells with a maximum response at 10 nmol/l(B cells) or at 100 nmol/l (D cells). Insulin secretion from perifused B cells was stimulated by GLP-I(7–37) (maximum at 10 nmol/l) and 10 nmol/l GLP-I(7–37) released somatostatin from perifused D cells, GLP-I(7–37) did not influence cAMP or glucagon secretion from A cells. These data indicate that pancreatic B and D cells, but not the A cells are influenced directly by GLP-I(7–37) via binding to specific receptors. Our findings support a model of physiologic regulation of insulin secretion whereby GLP-I(7–37) released from the intestine in response to oral nutrients potently stimulates insulin secretion via an endocrine mechanism that in turn may be dampened by a feed-back suppression by the release of somatostatin. In addition, suppression of the secretion of glucagon, a hormone whose actions are counter-regulatory to those of insulin, may occur by paracrine mechanisms involving GLP-I(7–37)-mediated stimulation of both insulin and somatostatin secretion.