Insulin clearance is different in men and women.

Insulin is often infused based upon total body weight (TBW) or fat-free mass (FFM) for glucose clamp protocols. We observed greater insulin concentrations in men than women using this approach and examined whether splanchnic insulin extraction accounts for the differences. Whole-body insulin clearance was measured during a pancreatic clamp study (somatostatin to inhibit islet hormone secretion) including 13 adults (6 men); and whole-body insulin clearance was measured during a euglycemic, hyperinsulinemic clamp study including 27 adults (13 men). Femoral artery and hepatic vein blood samples were collected to measure splanchnic insulin balance. For the pancreatic clamp study, insulin was infused at rates of 0.5, 1.0, and 2.0 mU/kg of TBW per minute; and for the euglycemic, hyperinsulinemic clamp study, insulin was infused at 2.5 mU/kg of FFM per minute. Significantly greater arterial insulin concentrations were found in men than women. Splanchnic plasma flow was similar in men and women in both protocols. Splanchnic insulin extraction and the fraction of infused insulin removed by splanchnic bed were significantly greater in men than in women. However, whole-body insulin clearance was greater in women than men. Infusing insulin per body weight or FFM results in higher plasma insulin concentrations in men than women. Splanchnic insulin extraction is greater in men, indicating that greater peripheral insulin clearance in women accounts for the sex differences we observed. This finding has implications for insulin clamp study design and raises the question of which tissues take up more insulin in women.