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.


CONCLUSIONS
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.
Third Department of Internal Medicine, Yamagata University School of Medicine, Japan.
K
K
Yamatani
S
S
Marubashi
K
K
Wakasugi
K
K
Saito
N
N
Sato
K
K
Takahashi
H
H
Sasaki
D000273:Adipose Tissue / Q000502:physiology; D000818:Animals; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000096:biosynthesis*; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000188:drug therapy / Q000378:metabolism*; D004614:Emaciation / Q000209:etiology / Q000503:physiopathology; D004837:Epinephrine / Q000494:pharmacology*; D005934:Glucagon / Q000494:pharmacology; D005947:Glucose / Q000032:analysis; D007328:Insulin / Q000627:therapeutic use; D007545:Isoproterenol / Q000494:pharmacology; D007773:Lactates / Q000494:pharmacology; D019344:Lactic Acid; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D010109:Oxymetazoline / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D011773:Pyruvates / Q000494:pharmacology; D019289:Pyruvic Acid; D051381:Rats; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000502:physiology; D013311:Streptozocin
D007328:Insulin; D007773:Lactates; D011773:Pyruvates; D011943:Receptors, Adrenergic, beta; D005576:Colforsin; D010656:Phenylephrine; D019344:Lactic Acid; D013311:Streptozocin; D019289:Pyruvic Acid; D010109:Oxymetazoline; D005934:Glucagon; D011433:Propranolol; D000242:Cyclic AMP; D005947:Glucose; D007545:Isoproterenol; D004837:Epinephrine