Hepatic glucose production and insulin sensitivity and responsiveness in iron-deficient anemic rats

We performed euglycemic hyperinsulinemic glucose clamps at insulin infusion rates of 1.9, 4.0, 9.3, and 19.3 mU.kg-1 x min-1 in rats with varying severities of iron deficiency anemia (IDA; mean hemoglobin concentrations of 59, 79, 107, and 137 g/l) to assess the effect of IDA on insulin sensitivity and responsiveness. Glucose appearance and disappearance (Rd) rates were determined using a primed continuous infusion of [3-3H]glucose. Basal plasma glucose and insulin concentrations were similar between the IDA and control rats. Basal hepatic glucose production was significantly (P = 0.0001) elevated in the two most anemic groups (13.6 +/- 2.4 and 12.6 +/- 3.1 vs. 10.6 +/- 2.2 and 10.2 +/- 2.0 mg.kg-1 x min-1). A significant upward shift in the insulin dose-response curves for Rd indicated an increase in peripheral insulin responsiveness in the two most anemic groups while a slight leftward shift was suggestive of an increase in insulin sensitivity in all three anemic groups. Hepatic insulin sensitivity and responsiveness were unaffected by IDA. We conclude that increased glucose utilization rates in IDA rats are due primarily to an increase in peripheral insulin responsiveness.