Simultaneous insulinlike growth factor I and insulin resistance in obese Zucker rats

It has recently been shown that the ability of insulinlike growth factor I (IGF-I) to stimulate glucose uptake and to lower circulating amino acid levels is retained in insulin-resistant diabetic BB rats. To examine in vivo effects of IGF-I in obese Zucker rats (another model of insulin resistance) 6 obese and 6 lean rats received euglycemic IGF-I infusions (0.65 nmol.kg-1.min-1). IGF-I-stimulated glucose uptake in obese rats was 50% lower than lean control rats (45.0 +/- 2.8 vs. 92.2 +/- 6.1 mumol.kg-1.min-1, respectively), even though the rise in circulating IGF-I levels was greater in the obese group during IGF-I infusion. In addition, branched chain amino acid concentrations that declined by 45% in lean controls were not suppressed significantly in obese rats (392 +/- 33 basal vs. 327 +/- 29 microM at 90 min). Equivalent results were observed during euglycemic insulin clamps (12 pmol.kg-1.min-1) in 7 obese and 11 lean rats. These studies demonstrate that obese Zucker rats are resistant to the effects of IGF-I and insulin on glucose and amino acid metabolism.