Hyperinsulinemia in GPX1 Overexpressing Mice is Independent of Obesity

Abstract

Our laboratory has previously reported insulin resistance, along with hyperglycemia, hyperinsulinemia and obesity, in Se-dependent glutathione peroxidase-1 (GPX1) overexpressing (OE) mice. A subsequent experiment has shown that a caloric restriction of the obese OE mice (10 months of age) for three months eliminated all of the phenotypes except for hyperinsulinemia. The objective of the present study was to determine if hyperinsulinemia, along with insulin resistance, in OE mice could be completely prevented by caloric restriction at a younger age prior to the onset of those disorders. A total of 24 OE and the wild-type (WT) male mice (2-month old, n = 6 per treatment-genotype) were fed a Se-adequate (0.4 mg Se/kg), torula yeast diet at 5 (full feeding) or 3 g per day (caloric restricted) for four months. There was no significant difference in any measure between the two genotypes at initial, and the full feeding OE mice developed all of previously-reported signs. With the caloric restriction, the OE mice had body weight, fasting blood glucose level and insulin sensitivity similar to those of the WT mice at the end of study (6 months of age). The caloric restricted OE mice still had higher (P < 0.05) plasma insulin level after overnight fasting (702 vs. 406 pg/mL), and at 15 min after a glucose challenge (1782 vs. 602 pg/mL) than the WT mice, respectively. Both restricted and full feeding OE mice demonstrated improved (P < 0.05) glucose tolerance than the WT mice. In conclusion, hyperinsulinemia either at fasting or upon glucose stimulation in the OE mice was independent of obesity, and could not be removed by caloric restriction even at the early age. [NIH DK 53018 to XGL]