Impaired function of pancreatic islets from rats with portal hypertension resulting from cirrhosis and partial portal vein ligation.
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.
Gomis
R
R
Endocrinology Unit, Hospital Clínic I Provincial, University of Barcelona, School of Medicine, Spain.
Fernández-Alvarez
J
J
Pizcueta
P
P
Fernández
M
M
Casamitjana
R
R
Bosch
J
J
Rodés
J
J
D000818:Animals; D002251:Carbon Tetrachloride; D005934:Glucagon / Q000378:metabolism; D006975:Hypertension, Portal / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology*; D066298:In Vitro Techniques; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000378:metabolism / Q000503:physiopathology*; D008026:Ligation; D008106:Liver Cirrhosis, Experimental / Q000139:chemically induced / Q000150:complications*; D008297:Male; D011169:Portal Vein / Q000601:surgery*; D051381:Rats; D017208:Rats, Wistar
D007328:Insulin; D005934:Glucagon; D002251:Carbon Tetrachloride