The Regulation of Splanchnic Glucose Production in Subjects with Low Insulin Response – a Compensatory Mechanism in Prediabetes?

Splanchnic exchange of glucose, pyruvate, lactate, glycerol and individual amino acids was measured in 22 healthy non‐obese men with normal glucose tolerance. Ten of the subjects had a diminished insulin response to glucose infusion and formed the group of low insulin responders. Basal insulin levels were significantly reduced in the latter group. In spite of this, the splanchnic glucose output was 45 per cent lower than in the controls. During the infusion of 2 mg glucose/kg/ min. for 45 min., a significant elevation of the arterial insulin concentration was observed only in the control group. However, splanchnic glucose output decreased more rapidly and to a greater extent in the low insulin responders despite significantly reduced insulin levels. The uptake of gluconeogenic precursors was similar in both groups. No differences were noted in the arterial glucagon levels. These findings are taken to indicate that hepatic sensitivity to endogenous insulin is augmented in low insulin responders, thereby providing a mechanism for maintaining normal glucose tolerance in the presence of subnormal insulin secretion.