Catecholamine-induced cAMP response in streptozotocin-induced diabetic rat liver

The effect of prolonged diabetic state on catecholamine-induced adenosine 3',5'-monophosphate (cAMP) response in the rat liver was examined using isolated liver perfusion. Epinephrine- or isoproterenol-induced cAMP production was enhanced (10-fold of the control) in the liver from extremely emaciated (intraperitoneal adipose tissue was absent completely) diabetic rats 4 weeks after streptozotocin-injection kept without insulin, but not from adipose tissue-present diabetic rats. Glucagon-induced cAMP production was decreased in the diabetic rat liver 4 weeks after streptozotocin regardless of the presence or absence of adipose tissue. Secretin-induced cAMP production was also decreased in the adipose tissue-absent diabetic rat liver. Plasma levels of glucose or insulin were not different between adipose tissue-present and -absent diabetic rats. Liver dysfunction (elevated AST and ALT levels) was observed 1 week after streptozotocin-injection, and worsened at 4 weeks. Forskolin-induced production of cAMP, and oxymetazoline (an alpha 2-adrenergic agonist)-induced suppression of it were not different among the control, newly diabetic (1 week after streptozotocin-injection), and the adipose tissue-absent diabetic rat liver.

1) enhanced beta-adrenergic, and decreased glucagon- or secretin-induced cAMP production seems to be caused by different mechanisms; 2) the prolonged severe diabetic state losing adipose tissue may cause a considerable change in metabolism and the characteristics of hepatocyte, and lead to enhanced beta-adrenergic cAMP production.