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

Tohoku J Exp Med. 1994 Jul;173(3):311-20. doi: 10.1620/tjem.173.311.

Abstract

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.

In conclusion: 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.

Publication types

  • Comparative Study

MeSH terms

  • Adipose Tissue / physiology
  • Animals
  • Colforsin / pharmacology
  • Cyclic AMP / biosynthesis*
  • Diabetes Mellitus, Experimental / complications
  • Diabetes Mellitus, Experimental / drug therapy
  • Diabetes Mellitus, Experimental / metabolism*
  • Emaciation / etiology
  • Emaciation / physiopathology
  • Epinephrine / pharmacology*
  • Glucagon / pharmacology
  • Glucose / analysis
  • Insulin / therapeutic use
  • Isoproterenol / pharmacology
  • Lactates / pharmacology
  • Lactic Acid
  • Liver / drug effects*
  • Liver / metabolism
  • Male
  • Oxymetazoline / pharmacology
  • Phenylephrine / pharmacology
  • Propranolol / pharmacology
  • Pyruvates / pharmacology
  • Pyruvic Acid
  • Rats
  • Receptors, Adrenergic, beta / drug effects
  • Receptors, Adrenergic, beta / physiology
  • Streptozocin

Substances

  • Insulin
  • Lactates
  • Pyruvates
  • Receptors, Adrenergic, beta
  • Colforsin
  • Phenylephrine
  • Lactic Acid
  • Streptozocin
  • Pyruvic Acid
  • Oxymetazoline
  • Glucagon
  • Propranolol
  • Cyclic AMP
  • Glucose
  • Isoproterenol
  • Epinephrine