Functional receptors for the insulinotropic hormone glucagon-like peptide-I(7-37) on a somatostatin secreting cell line.
Glucagon-like peptide-I(7-37) [(GLP-I(7-37)] is an intestinal 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 hormone secretion was studied using cell lines producing insulin/B cell (beta TC-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.
Fehmann
H C
HC
Laboratory of Molecular Endocrinology, Massachusetts General Hospital, Boston 02114.
Habener
J F
JF
D000818:Animals; D001667:Binding, Competitive; D002460:Cell Line; D000242:Cyclic AMP / Q000378:metabolism; D005934:Glucagon / Q000737:chemistry*; D052216:Glucagon-Like Peptide 1; D000067757:Glucagon-Like Peptide-1 Receptor; D004763:Glucagon-Like Peptides; D005947:Glucose / Q000494:pharmacology; D006728:Hormones / Q000378:metabolism / Q000494:pharmacology; D066298:In Vitro Techniques; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000166:cytology / Q000378:metabolism*; D010446:Peptide Fragments / Q000494:pharmacology; D010455:Peptides / Q000378:metabolism* / Q000494:pharmacology; D052336:Proglucagon; D011498:Protein Precursors / Q000737:chemistry*; D051381:Rats; D011956:Receptors, Cell Surface / Q000378:metabolism; D018027:Receptors, Glucagon; D012636:Secretory Rate / Q000187:drug effects; D013004:Somatostatin / Q000378:metabolism
C000593835:Glp1r protein, rat; D000067757:Glucagon-Like Peptide-1 Receptor; D006728:Hormones; D007328:Insulin; D010446:Peptide Fragments; D010455:Peptides; D011498:Protein Precursors; D011956:Receptors, Cell Surface; D018027:Receptors, Glucagon; D013004:Somatostatin; D052336:Proglucagon; D004763:Glucagon-Like Peptides; D052216:Glucagon-Like Peptide 1; D005934:Glucagon; D000242:Cyclic AMP; D005947:Glucose; C051322:glucagon-like peptide 1 (7-37)