Liver glycogen catabolism in young adult Goto-Kakizaki rats

Liver glycogen catabolism was investigated in young adult Goto-Kakizaki rats (GK group) and compared with non-diabetic Wistar rats (Control group). The diabetic condition of GK rats was confirmed by hyperglycemia and insulin resistance. Glycogen catabolism was intensified during the infusion of epinephrine (10 μM, 20 μM, and 40 μM), phenylephrine (2 μM, 4 μM, and 6 μM), and glucagon (1 nM) in both Control and GK livers. The degree of glycogen catabolism during these infusions was similar in Control and GK rats, despite the higher liver glycogen content observed in the GK rats. However, a diminished intensification of hepatic glucose production was observed in GK rats during the infusion of isoproterenol (10 μM, 20 μM, and 40 μM). To further investigate this difference, the effect of cAMP, the intracellular mediator of isoproterenol, on liver glycogen catabolism was examined. Livers from GK rats showed no response to 3 μM and 5 μM cAMP but displayed a similar intensification of glycogen catabolism at 7 μM and 9 μM cAMP as the Control group. Interestingly, a higher intensification of glycogen catabolism was observed in GK livers during the infusion of 3 μM dibutyryl-cAMP, a phosphodiesterase-resistant cAMP analog, suggesting that cAMP inactivation by phosphodiesterases might be increased in GK livers. While these findings suggest a possible involvement of phosphodiesterases in the reduced response to isoproterenol, the evidence is insufficient to conclusively establish this mechanism. It can be concluded that liver glycogenolysis does not contribute to the hyperglycemia and glucose intolerance observed in young adult GK rats and that cAMP-mediated intracellular signaling appears to be attenuated in the livers of these animals.