HYPERTRIGLYCERIDEMIC MICE TRANSGENIC FOR THE HUMAN APOLIPOPROTEIN C-III GENE ARE NEITHER INSULIN-RESISTANT NOR HYPERINSULINEMIC

Plasma glucose and insulin concentrations and in vivo and in vitro estimates of insulin action were compared in hypertriglyceridemic apolipoprotein C-III transgenic mice (mean +/- SE triglyceride concentration = 11.8 +/- 0.9 mmol/l) and their normotriglyceridemic (1.1 +/- 0.1 mmol/l) littermates. There were no differences in the glucose (8.9 +/- 0.2 vs. 9.3 +/- 0.5 mmol/l) or insulin (172 +/- 21 vs. 203 +/- 17 pmol/l) concentrations of the transgenic and control mice, respectively. Steady state plasma glucose concentrations at the end of a 150-min period of physiological hyperinsulinemia were also in transgenic (6.2 +/- 0.5 mmol/l) and control mice (6.7 +/- 0.5 mmol/l). As the steady-slate plasma insulin levels were essentially identical in the two groups (similar to 1000 pmol/l), these results show that whole body insulin-mediated glucose disposal was unchanged in the transgenic mice. Finally, values for isoproterenol-stimulated lipolysis, insulin-inhibition of lipolysis, and insulin-stimulated glucose disposal were similar in adipocytes isolated from transgenic and control mice. It can be concluded from these data that insulin resistance does not develop in hypertriglyceridemic mice transgenic for the human apolipoprotein C-III gene.