Effect of triiodothyronine on glucose utilization in diaphragm of obese (ob/ob) mice

Genetically obese-hyperglycemic (ob/ob) mice are hypothyroid, hyperinsulinemic, and insulin resistant. Because muscle plays an important role in glucose homeostasis, the role of triiodothyronine (T3) in regulation of insulin-sensitive glucose utilization by muscles of obese mice was examined. Four doses of T3, 5.0, 12.5, 25.0, and 50.0 micrograms/100 g body weight were injected, i.p., into obese and nonobese mice daily from 3 weeks until 6 weeks of age. Food consumption and body weight were decreased at lower doses of T3 and increased at higher doses of T3 in both obese and nonobese mice. By 6 weeks of age all doses of T3 treatment increased oxygen consumption in both genotypes. At 6 weeks of age, the diaphragms from the saline-injected nonobese mice had greater in-vitro insulin-stimulated glucose utilization than muscles from the saline-injected obese mice. Both anaerobic and aerobic glucose oxidation were increased by T3 treatment, but the obese had greater increases than those observed in muscles from nonobese mice. Muscles from obese mice increased insulin-stimulated glucose utilization by T3 treatment to that of the nonobese level, whereas there was no change in insulin-stimulated glucose utilization of nonobese mice. Muscle glycogen synthesis in obese and nonobese mice was decreased with very high T3 doses. A higher dose of T3 was required to increase glucose utilization in the obese muscles than in the nonobese muscles. The results suggest that a functional hypothyroidism or T3 resistance may be an early part of this particular obesity syndrome.