Catecholamine-Induced cAMP Response in Streptozotocin-Induced Diabetic Rat Liver.

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 tissuepresent 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 «2-adrenergic agonist)-induced suppression of it were not different among the control, newly diabetic (1 week after streptozotocininjection), and the adipose tissue-absent diabetic rat liver. In conclusion: 1) enhanced f3-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 fl-adrenergic cAMP production.streptozotocin-induced diabetic rat liver; adenosine 3', 5'-monophosphate (CAMP); caecholamine; glucagon; secretin It is well known that catecholamines stimulate through al-and R2-adrenergic receptors. The relative receptors in the rat liver depends on age (Sherline et al. sex (Studer and Borle 1982) and pathological conditions. hepatic glycogenolysis potency of these two 1974; Blair et al. 1979),In the normal male rat

Increased Epinephrine-Induced cAMP Response in Severely Diabetic BB/W Rat Liver.

“…We recently found that epinephrineand isoproterenol-induced cAMP production was markedly enhanced in the liver of extremely emaciated diabetic rats without adipose tissue, but not in the liver of diabetic rats with preserved adipose tissue, 4 weeks after streptozotocininjection and kept without insulin [9]. But liver dysfunction was observed when streptozotocininjected rats were kept without insulin, as reported by Lauguens et al [10].…”

“…Expression of the a-adrenergic receptor gene [25] but not of the f3-adrenergic receptor gene [26] has been confirmed in the normal rat liver. In our previous study [9], cAMP response which was dose-dependently enhanced by catecholamines was observed only in the liver of adipose tissue-absent streptozotocin-induced diabetic rats. As expected, epinephrine-induced cAMP response was enhanced only in liver from adipose tissue-absent diabetic BB/W rats, so that the complete loss of intraperitoneal adipose tissue in addition to diabetes appeared to be required for enhancement of catecholamine-induced cAMP response in rat liver.…”

“…When streptozotocin-induced diabetic rats were kept without insulin, liver dysfunction was observed [9]. Streptozotocin is known to be hepatotoxic [10].…”

“…Surprisingly, liver dysfunction was observed on blood chemistry testing in adipose tissue-absent diabetic BB/W rats, but not when adipose tissue was preserved. In adipose tissueabsent diabetic BB/W rats, LW/BW was high, but no remarkable histological change was observed, so that the liver dysfunction observed in adipose tissue-absent diabetic BB/W rats appeared to differ from that in streptozotocin-induced diabetic [9,10], partially hepatectomized [11] and cholestatic [12] rats. In adipose tissue-absent diabetic BB/W rats, plasma glucose was higher, plasma insulin was lower, and islet destruction was greater than in adipose tissue-preserved diabetic BB/W rats.…”

Outcome of Capparis Spinosa Fruit Extracts Treatment on Liver, Kidney, Pancreas and Stomach Tissues in Normal and Diabetic Rats

“…The AST (Aspartate aminotransferase) and ALT (Alanine aminotransferase) are two appropriate markers to assess the level of liver damage [24]. Dysfunction of liver associate to increase levels of AST and ALT and these changes were observed in our STZ-induced DM model, one week after STZ injection which got worsened at about 4 weeks later [25]. Note that the ALT is a specific index for healthy liver cells, while AST presents in other tissues rather than liver, so has less specificity [26].…”