Calcitonin gene-related peptide inhibits insulin secretion studies on ion fluxes and cyclic AMP in isolated rat islets.
Calcitonin gene-related peptide (CGRP) is an intrapancreatic neuropeptide that is known to inhibit glucose-stimulated insulin secretion in rats. To study if this inhibition is a direct islet effect, isolated, overnight cultured, rat islets were incubated together with glucose (3.3 or 8.3 mM) and CGRP (10(-11) to 10(-6) M). It was found that insulin secretion stimulated by glucose (8.3 mM) was inhibited by 77% by CGRP at 10(-6) M (p less than 0.001) and by 48% by the peptide at 10(-7) M (p less than 0.05). To study the possible mechanism(s) behind this inhibition, we investigated the effects of CGRP (10(-6) M) on the efflux of 45Ca2+ and 86Rb+ (reflecting Ca2+ and K+ ion movements, respectively) from isolated, perifused, rat islets. Furthermore, we examined the influence of CGRP on the content of cyclic AMP in overnight cultured isolated rat islets. We found that the initial, immediate 2-8 min peak of glucose (16.7 mM)-stimulated 45Ca(2+)-efflux was not affected by CGRP. In contrast, when the peptide was added at min 20 after glucose introduction, i.e., when the peak 45Ca(2+)-efflux had vanished, a small decrease in 45Ca(2+)-efflux was observed (p less than 0.001). CGRP did not alter the 86Rb(+)-efflux at 8.3 mM glucose neither in the presence nor in the absence of extracellular Ca2+. The islet content of cyclic AMP after 30 min incubation was 19.1 +/- 3.1 fmol/islet at 3.3 mM glucose and increased to 36.0 +/- 5.7 fmol/islet at 16.7 mM glucose (p less than 0.05). CGRP (10(-6) M) completely abolished this increase.(ABSTRACT TRUNCATED AT 250 WORDS)
Pettersson
M
M
Department of Pharmacology, Lund University, Sweden.
Ahrén
B
B
D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism*; D003981:Diazoxide / Q000494:pharmacology; D005947:Glucose / Q000494:pharmacology; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D011188:Potassium / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D012413:Rubidium / Q000378:metabolism
D007328:Insulin; D000242:Cyclic AMP; D005947:Glucose; D015740:Calcitonin Gene-Related Peptide; D012413:Rubidium; D003981:Diazoxide; D011188:Potassium; D002118:Calcium