Increased circulating
insulin and
glucagon levels are a common observation in patients with
cirrhosis, as well as in portal hypertensive models.
Hyperinsulinemia and hyperglucagonemia may be caused either by increased beta- and alpha-cell secretion or by defective hepatic clearance of these
hormones. To elucidate whether an abnormal endocrine pancreatic function might contribute to the
hyperinsulinism or to the hyperglucagonism observed in chronic
portal hypertension,
insulin and
glucagon secretion were measured in vitro in isolated pancreatic islets from rats with partial portal vein ligated and rats with
cirrhosis caused by
carbon tetrachloride poisoning. Both rats with partial portal vein
ligation and rats with
cirrhosis caused by
carbon tetrachloride poisoning exhibited
hyperinsulinism and hyperglucagonism as compared with control rats. Isolated pancreatic islets from both experimental portal hypertensive models showed an impaired insulin secretion after
glucose stimulation. On the contrary,
glucagon secretion was significantly increased, and there was a markedly enhanced response to
arginine. This increased in vitro
glucagon production could not be corrected, even in the presence of high
glucose concentrations in the incubation medium. Therefore our data show that although hyperglucagonism in rats with partial portal vein
ligation and in rats with
cirrhosis caused by
carbon tetrachloride poisoning is promoted by an enhanced alpha-cell secretion,
hyperinsulinism is associated with impaired beta-cell secretion.