Development of insulin resistance in the rat is dependent on the rate of glucose absorption from the diet.

The effect of long-term consumption of diets of different carbohydrate composition was investigated be feeding rats for up to 52 wk on diets in which the carbohydrate was either glucose, amylose or amylopectin. A glucose-based diet was included to examine the relationship between the rate of carbohydrate absorption from the diet and the development of insulin resistance. Insulin sensitivity was assessed by subjecting animals to an intravenous glucose tolerance test (IVGTT). Amylopectin-fed animals became progressively insulin resistant from 12 to 26 wk of feeding. The area under the plasma insulin curves in response to a glucose load (IVGTT) for these animals rose progressively from 15.1 +/- 2.5 nmol/L.30 min at 8 wk to 45.8 +/- 3.5 nmol/L.30 min (P < 0.001) at 26 wk of feeding. Amylose-fed animals did not exhibit insulin resistance until 26 wk of feeding when insulin secretion in response to a glucose load was 28.3 +/- 0.9 vs. 14.6 +/- 3.2 nmol/L.30 min at 16 wk of feeding (P < 0.005). Glucose-fed animals displayed insulin resistance after only 8 wk of feeding. At this time, the area under their plasma insulin curves was almost double that for amylose- or amylopectin-fed animals (P < 0.001). We conclude that long-term consumption of a diet in which available carbohydrate is rapidly absorbed causes insulin resistance in rats. The more rapidly glucose is absorbed from the diet, the faster the insulin resistance develops.