Adrenergic modulation of pancreatic somatostatin, insulin, and glucagon secretion: evidence for differential sensitivity of islet A, B, and D cells.
To characterize the adrenergic effects of epinephrine on somatostatin, insulin and glucagon release and to assess the potential interactions of islet A, B, and D cell function, isolated rat islets were incubated in vitro with epinephrine (0.05-20 microM) in the presence and absence of the alpha adrenergic antagonist, phentolamine (2 or 4 microM), and/or the beta adrenergic antagonist, propranolol (2 microM). At concentrations of epinephrine at or less than 1 microM, somatostatin and insulin release were inhibited while glucagon release was unaffected. At greater epinephrine concentrations, somatostatin and glucagon release were increased while insulin release was further suppressed. The threshold as well as the half-maximal effect of epinephrine occurred at lower concentrations for somatostatin release than for insulin and glucagon release. The inhibitory effect of 0.5 microM epinephrine on somatostatin and insulin release was completely reversed by phentolamine and was unaffected by propranolol. The stimulatory effect of 2 and 20 microM epinephrine on somatostatin and glucagon release was not observed when propranolol was included in the incubation medium along with epinephrine. These results demonstrate that rat islet A, B, and D cells differ in their sensitivity to alpha and beta adrenergic effects. At low concentrations of epinephrine, alpha adrenergic effects on D cells predominate over beta adrenergic effects whereas at greater concentrations of epinephrine alpha and beta effects appear to be equal; alpha adrenergic effects of epinephrine predominate over those of beta on the B cell at least up to 20 microM epinephrine: exclusively beta adrenergic effects of epinephrine are observed on the A cell at least up to 20 microM epinephrine.
D000818:Animals; D004837:Epinephrine / Q000494:pharmacology; D005934:Glucagon / Q000378:metabolism*; D066298:In Vitro Techniques; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000294:innervation / Q000378:metabolism*; D010646:Phentolamine / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013004:Somatostatin / Q000378:metabolism*; D013564:Sympathetic Nervous System / Q000502:physiology*
D007328:Insulin; D013004:Somatostatin; D005934:Glucagon; D011433:Propranolol; D004837:Epinephrine; D010646:Phentolamine