The prevalence of obesity and type 2 diabetes (T2DM) is a major health burden. Insulin resistance is readily inducible with high-fat feeding in rats. Previous studies have shown that diet-induced insulin resistance can be reversed by a single oral glucose meal. In this study, we tested whether insulin resistance was also ameliorated by intravenous infusion of glucose.
Male Wistar rats were fed ad libitum either standard chow or high fat (45% of energy as saturated fat from lard) diet for three weeks. Jugular vein cannulas were placed surgically and insulin sensitivity was assessed using the hyperinsulinemic-euglycemic clamp technique with concomitant infusion of 3H glucose and 14C 2-deoxyglucose. The evening before the clamp, high fat fed rats were divided into three groups and received either isocaloric meals of high fat (HF), high glucose (HG) or an intravenous glucose infusion (IVG). Chow fed rats received their usual chow meal (C).
Basal blood glucose and clamped plasma glucose levels were not different between groups. HF rats had significantly lower GIR (10.1±0.8 mg/kg/min) than C rats (16.4±0.6, p<0.001), indicative of insulin resistance. HF rats infused with glucose (IVG) were also insulin resistant (GIR 12.1±0.7, p<0.01 vs C), and not different to HF rats. HG rats fed a single glucose meal instead of the usual fat meal had a significantly higher GIR (15.2±1.0) than HF (P<0.001) or IV glucose (p=0.067), but not different to C. Preliminary analysis of tracer derived glucose metabolism parameters indicates glucose disposal (Rd) in HG rats was markedly increased compared with HF rats (p<0.05), and insulin-stimulated muscle glucose uptake (Rg’) was reduced in IVG but not HG rats compared with C.
These results suggest that glucose-mediated reversal of whole body insulin resistance in fat fed rats may be dependent on digestion and absorption of the glucose meal by the gastrointestinal tract.