Abstract
Glucagon, the pancreatic hormone secreted in response to hypoglycemia, is a key regulator of hepatic glucose production. Since the number of specific glucagon receptors expressed on the cell surface affects the sensitivity of the liver to glucagon, we have examined the regulation of glucagon receptor mRNA levels in cultured primary rat hepatocytes. By ribonuclease protection assay we have identified glucose and intracellular cAMP as regulators of glucagon receptor mRNA expression in cultured rat hepatocytes. We observed a concentration-dependent increase in glucagon receptor mRNA expression when hepatocytes were cultured in the presence of increasing glucose. A 2-fold induction in glucagon receptor mRNA levels was obtained in hepatocytes cultured for 24 h with 22.5 mM glucose as compared with 5.5 mM glucose. Factors such as 3-isobutyl-1-methylxanthine (IBMX), isoproterenol, and forskolin, which are known to raise intracellular cAMP levels, all caused a reduction in glucagon receptor mRNA expression. IBMX alone, IBMX together with isoproterenol, and forskolin reduced glucagon receptor mRNA expression to approximately 25, 10, and 50%, respectively. Glucagon was found to dose dependently decrease glucagon receptor mRNA expression ...Continue Reading
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