Inhibition of insulin secretion by betagranin, an N-terminal chromogranin A fragment.
Betagranin, an N-terminal fragment of chromogranin A, results from a proteolytic processing, and is co-secreted with insulin. While other chromogranin A-derived peptides negatively modulate hormone secretion, the role of betagranin in pancreatic beta-cells is so far unknown. We have recently shown that pancreatic islet betagranin levels are down-regulated in obese, leptin-deficient mice. In the present study, we have investigated the distribution of betagranin in primary mouse islets and cells of the MIN6 line and have evaluated its effects on insulin secretion. We showed that betagranin co-localizes with insulin within secretory granules and strongly inhibited insulin secretion in response to both glucose and potassium, by blocking the influx of calcium. The data demonstrated a hitherto unknown inhibitory effect of betagranin on insulin secretion.
Schmid
Gerhard M
GM
Biomedical Proteomics Research Group (BPRG), Department of Structural Biology and Bioinformatics, Geneva University Medical Center, CH-1211 Geneva 4, Switzerland.
Meda
Paolo
P
Caille
Dorothée
D
Wargent
Ed
E
O'Dowd
Jacqueline
J
Hochstrasser
Denis F
DF
Cawthorne
Michael A
MA
Sanchez
Jean-Charles
JC
D000818:Animals; D020013:Calcium Signaling / Q000187:drug effects*; D002460:Cell Line; D002864:Chromogranins / Q000494:pharmacology*; D005260:Female; D005947:Glucose / Q000378:metabolism / Q000494:pharmacology; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000378:metabolism* / Q000648:ultrastructure; D051379:Mice; D011188:Potassium / Q000378:metabolism / Q000494:pharmacology; D013549:Sweetening Agents / Q000494:pharmacology
D002864:Chromogranins; D007328:Insulin; D013549:Sweetening Agents; C046560:beta-granins; D005947:Glucose; D011188:Potassium