Fig. 4.

A demonstration of the “paradoxical” stimulation of glucagon secretion by hyperglycemia when unaccompanied by a concomitant increase in insulin. These experiments were performed in hypoinsulinemic alloxan-diabetic dogs, in which glucose was infused at a rate of 8.8 mg/kg/min to worsen the hyperglycemia. As blood glucose increased without an increase in insulin, glucagon levels increased paradoxically. Similar results have been obtained in cultured α-cells. These findings suggest that, in T1DM, the hyperglycemia induced by carbohydrate ingestion may be further exaggerated by inappropriate glucagon-stimulated hepatic glucose production [Figure modified from Braaten et al. (21)].