Circulating concentrations of the adipocyte protein adiponectin are decreased in parallel with reduced insulin sensitivity during the progression to type 2 diabetes in rhesus monkeys

Adiponectin is an adipose-specific plasma protein whose plasma concentratio ns are decreased in obese subjects and type 2 diabetic patients. This prote in possesses putative antiatherogenic and anti-inflammatory properties. In the current study, we have analyzed the relationship between adiponectin an d insulin resistance in rhesus monkeys (Macaca mulatta), which spontaneousl y develop obesity and which subsequently frequently progress to overt type 2 diabetes. The plasma levels of adiponectin were decreased in obese and di abetic monkeys as in humans. Prospective longitudinal studies revealed that the plasma levels of adiponectin declined at an early phase of obesity and remained decreased after the development of type 2 diabetes. Hyperinsuline mic-euglycemic clamp studies revealed that the obese monkeys with lower pla sma adiponectin showed significantly lower insulin-stimulated peripheral gl ucose uptake (M rate). The plasma levels of adiponectin were significantly correlated to M rate (r = 0.66,P < 0.001). Longitudinally, the plasma adipo nectin decreased in parallel to the progression of insulin resistance. No c lear association was found between the plasma levels of adiponectin and its mRNA levels in adipose tissue. These results suggest that reduction in cir culating adiponectin may be related to the development of insulin resistanc e.