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

TLDR

Adiponectin, an adipose‑specific plasma protein, is reduced in obesity and type 2 diabetes and is thought to have anti‑atherogenic and anti‑inflammatory effects. The study examined how circulating adiponectin levels relate to insulin resistance in rhesus monkeys that naturally develop obesity and type 2 diabetes. In rhesus monkeys, plasma adiponectin fell early during obesity, remained low after diabetes onset, and its decline tracked insulin resistance, with lower levels correlating with reduced insulin‑stimulated glucose uptake and a strong association with the M rate, indicating that reduced circulating adiponectin may contribute to insulin resistance.

Abstract

Adiponectin is an adipose-specific plasma protein whose plasma concentrations are decreased in obese subjects and type 2 diabetic patients. This protein possesses putative antiatherogenic and anti-inflammatory properties. In the current study, we have analyzed the relationship between adiponectin and insulin resistance in rhesus monkeys (Macaca mulatta), which spontaneously develop obesity and which subsequently frequently progress to overt type 2 diabetes. The plasma levels of adiponectin were decreased in obese and diabetic 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. Hyperinsulinemic-euglycemic clamp studies revealed that the obese monkeys with lower plasma adiponectin showed significantly lower insulin-stimulated peripheral glucose uptake (M rate). The plasma levels of adiponectin were significantly correlated to M rate (r = 0.66, P < 0.001). Longitudinally, the plasma adiponectin decreased in parallel to the progression of insulin resistance. No clear association was found between the plasma levels of adiponectin and its mRNA levels in adipose tissue. These results suggest that reduction in circulating adiponectin may be related to the development of insulin resistance.