HYPERGLYCEMIA INHIBITS GLUCOSE PRODUCTION IN MAN INDEPENDENT OF CHANGES IN GLUCOREGULATORY HORMONES

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Abstract
To evaluate the influence of hyperglycemia on hepatic glucose output in the absence of a rise in insulin, glucose was infused for 2 hours into six juvenile-onset diabetics receiving a constant infusion of insulin at a rate of 0.05–0.15 mU kg-1min-1. Prior to the infusion of glucose, insulin administration resulted in stable levels of plasma glucose (76±8 mg/dl) and glucose output (1.9±0.1 mg kg-1min-1). The addition of glucose produced a 2–3 fold rise in plasma glucose and a prompt fall in glucose output to 0.2–0.4 mg kg-1min-1, despite the unchanged rate of insulin infusion and the absence of a reduction in plasma glucagon or catecholamines. A similar decline in glucose output was observed when exogenous glucagon (1 ng kg-1min-1) was added to the glucose infusion. We conclude that in the presence of basal insulin levels hyperglycemia inhibits glucose output independent of a rise in insulin or a fall in anti-insulin hormones.