Pancreastatin Inhibits Insulin Secretion and Stimulates Glucagon Secretion in Mice

Recently a new peptide, pancreastatin, was isolated from porcine pancreatic extracts. It contains 49 amino acids and shows a structural similarity to chromogranin A, which occurs in secretory granules of the endocrine pancreas. Furthermore, pancreastatin has been found to inhibit glucose-induced insulin secretion in the perfused rat pancreas. However, its effects under in vivo conditions have never been studied. We have therefore investigated the effects of this peptide on insulin and glucagon secretion in vivo in the mouse. We found that an intravenous injection of pancreastatin (4.0 nmol/kg) lowered basal plasma insulin concentration at 6 min from 55 ± 8 μU/ml in control mice to 21 ± 7 microU/ml (P < .01). The peptide also inhibited the plasma insulin response to both glucose (P < .01) and the cholinergic agonist carbachol (P < .001). Furthermore, 2 min after injection of pancreastatin, plasma glucagon concentration had increased to 301 ± 19 pg/ml compared to 190 ± 12 pg/ml in control mice (P < .001). The peptide did not, however, affect the carbachol-induced plasma glucagon response. In addition, pancreastatin induced a transient hyperglycemia. Combined adrenergic blockade by means of a pretreatment of phentolamine and propranolol did not prevent pancreastatin from exerting its effects on plasma insulin levels, whereas the increase in plasma glucagon levels was abolished. Thus, in the mouse, the newly discovered intrapancreatic peptide pancreastatin 1) lowers baseline plasma insulin levels, 2) inhibits glucose- and cholinergically induced insulin secretion, 3) stimulates baseline glucagon secretion, and 4) induces hyperglycemia. The effects seen were modest in potency, and the effects on plasma insulin levels were seen also after combined α- and β-adrenoreceptor antagonism. We suggest that pancreastatin could be a regulator of islet function.