Evidence that hyperglycaemia per se does not inhibit hepatic glucose production in man

Summary

The effect of hyperglycaemia on hepatic glucose production (R _a ) was investigated in nine healthy men using sequential clamp protocols during somatostatin infusion and euglycaemia (0–150 min), at plasma glucose levels of 165 mg · dl⁻¹ (9.2 mM, 150–270 min) and during insulin infusion (1.0 mU · kg⁻¹ · min⁻¹, 270–360 min) in study 1 or during hypo-insulinaemia and plasma glucose levels of 220 mg · dl⁻¹ (12.2 mM; 270–390 min) in study 2. Somatostatin decreased R _a and glucose disposal rate (R _d ) but increased plasma free fatty acids (FFA) and lipid oxidation during euglycaemia. Increasing plasma glucose to 165 mg · dl⁻¹ (9.2 mM) and hypo-insulinaemia increased R _d , but no suppressive effects on R _a , plasma FFA and lipid oxidation were observed. By contrast hyperinsulinaemia (study 1), as well as a further increase in plasma glucose (study 2), both decreased R _a . However, more pronounced hyperglycaemia increased insulin secretion despite somatostatin resulting in a fall in plasma FFA and lipid oxidation. Our data questions the accepted dogma that hyperglycaemia inhibits R _a independently of insulin action.