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

YAMATANI, K., MARUBASHI, S., WAKASUGI, K., SAITO, K., SATO, N., TAKAHASHI, K. & SASAKI, H. Catecholamine-Induced cAMP Response in Streptozotocin-Induced Diabetic Rat Liver. Tohoku J. Exp. Med., 1994, 173 (3), 311-320-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 α2-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. In conclusion: 1) enhanced β-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 β-adrenergic cAMP production.