Mechanisms responsible for the hyperglycemia produced by the dibutyryl derivative of cyclic 3′,5′-adenosine monophosphate

Abstract

Glucose release by the liver and glucose uptake from the blood were measured in intact unanesthetized dogs in the postabsorptive state by the use of 14C-glucose. Plasma insulin concentrations were monitored by radioimmunoassay. It was found that the hyperglycemia resulting from the infusion (at 5 mg/kg/hr, i.v.) of N 6-2′- O-dibutyryl cyclic 3′,5′-adenosine monophosphate (dibutyryl cAMP) was due for the most part to increased glucose release. Plasma insulin concentration rose to the same level during dibutyryl cAMP infusion as during a comparable hyperglycemia produced by intravenous infusion of glucose. It is concluded that dibutyryl cAMP, at a concentration sufficient for a pronounced hepatic response, exerts no direct action on the β cells in vivo to enhance or inhibit glucose-stimulated insulin release. At the same elevated plasma insulin level, glucose uptake was increased less during dibutyryl cAMP hyperglycemia than during the comparable hyperglycemia caused by glucose infusion. It is concluded that a small part of the hyperglycemia maintained by dibutyryl cAMP is due to resistance on the part of the tissues to insulin-stimulated glucose uptake. When epinephrine was infused to yield a comparable hyperglycemia, glucose release from the liver increased but the plasma insulin concentration and the uptake of glucose by the tissues did not increase.