Evaluation of enhanced glucagon sensitivity as the cause of glucose intolerance in acutely uremic rats

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Abstract
These studies were undertaken to evaluate the possibility that increased hepatic glucose output, secondary to enhanced glucagon sensitivity, contributes to the glucose intolerance of acute uremia. In order to accomplish this, we determined the effect of an infusion of glucagon (6 ng/kg per min) on hepatic glucose output from isolated perfused livers of acutely uremic and sham-operated rats. Hepatic glucose output by livers from sham-operated rats more than doubled during glucagon infusion. In contrast, hepatic glucose output did not increase when livers of acutely uremic rats were perfused with glucagon. Furthermore, glycogen content did not fall nor did urea formation increas when livers from acutely uremic rats perfused with glucagon. On the other hand, dibutyryl cAMP infusion led to a similar increase in hepatic glucose output by livers from sham-operated and acutely uremic rats. Furthermore, urea formation increased and glycogen content decreased when livers from acutely uremic rats were perfused with dibutyryl cAMP. These results indicate that livers from acutely uremic rats exhibit a diminished responsiveness to glucagon-induced glycogenolysis and gluconeogenesis, but respond normally to dibutyryl cAMP. Thus, an increase in hepatic glucose output, secondary to enhanced glucagon sensitivity, does not appears to contribute to glucose intolerance in acutely uremic rats.