Sensitivity of rat pancreatic A and B cells to somatostatin.
Islet A and B cells were purified from the rat pancreas and examined for their respective sensitivity to somatostatin. Both somatostatin-14 (S14) and -28 (S28) inhibited glucagon and insulin release through direct interactions with the corresponding cell types. A dose-dependent suppression of the secretory activities was paralleled by a reduction in cellular cyclic AMP formation with similar ED50 values for both actions. The somatostatin effects on pancreatic hormone release may thus be mediated via an inhibition of adenylate cyclase activity. In pancreatic A cells, S14 and S28 were equally potent inhibitors with ED50 values ranging from 2 x 10(-12) to 2 x 10(-11) mol/l. Pancreatic B cells exhibited a similar sensitivity to S28 as the A cells (ED50 of 2 to 5 x 10(-11) mol/l), but not to S14 (ED50 of 2 x 10(-9) mol/l). Extrapolation of these in vitro sensitivities of islet A and B cells to the in vivo situation suggests that both cell types can respond to circulating S28 levels and that A cells are sensitive to both locally and distally released S14. Islet B cells appear insensitive to the normal peripheral S14 levels but could respond to locally released somatostatin. The marked difference in the sensitivities of islet A and B cells to S14 suggest that these cell types are equipped with different somatostatin receptors. This notion was further supported by the cell-selective actions of the synthetic S14 analogues [D-Trp8, D-Cys14]S14 and desAsn5[D-Trp8, D-Ser13]S14.
Schuit
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FC
Department of Biochemistry, Vrije Universiteit Brussel, Belgium.
Derde
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MP
Pipeleers
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DG
D000818:Animals; D002449:Cell Aggregation; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism; D005934:Glucagon / Q000378:metabolism*; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D013004:Somatostatin / Q000031:analogs & derivatives / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D007328:Insulin; D013004:Somatostatin; D005934:Glucagon; D000242:Cyclic AMP