Decrease in triglyceride accumulation in tissues by restricted diet and improvement of diabetes in Otsuka Long-Evans Tokushima fatty rats, a non-insulin-dependent diabetes model

Metabolism. 2000 Jan;49(1):108-14. doi: 10.1016/s0026-0495(00)90913-2.


With respect to the connection between triglyceride (TG) and non-insulin-dependent diabetes mellitus (NIDDM), previous reports have shown that TG accumulation in the liver and muscle is one of the causes of insulin resistance, and TG accumulation in pancreatic islets induces impairment of pancreatic beta-cell function. This experiment examined the relationship between an amelioration of hypertriglyceridemia (HTG), a decrease in TG accumulation in tissues, and an improvement of NIDDM by food restriction. In this experiment using Otsuka Long-Evans Tokushima fatty (OLETF) rats developing NIDDM and Long-Evans Tokushima Otsuka (LETO) rats as controls, sequential changes in body weight and TG content in tissue were measured and biochemical blood tests, an insulin euglycemic clamp test, and histopathologic examination of the pancreas and liver were performed. OLETF rats were allocated to a food-satiated group (satiated) or 30% food-restricted group (restricted). As a result, several findings were more evident in the restricted group than in the satiated group: (1) reductions in body weight and intraabdominal fat weight, decreases in plasma TG, insulin, and glucose levels, a decrease in the TG secretion rate, and an increase in plasma lipoprotein lipase (LPL) activity, (2) decreases in the TG content in the liver, pancreas, and muscle, (3) improvement of the glucose infusion rate (GIR), and (4) a marked reduction of TG accumulation in the liver and pancreatic islets on histopathologic examination. These results indicate that the improved HTG caused a reduction in TG accumulation in the liver and muscle, thereby improving insulin resistance. Moreover, the decrease in TG accumulation in pancreatic islets suggests an improvement of pancreatic beta-cell function.

MeSH terms

  • Animals
  • Blood Glucose / metabolism
  • Body Weight
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / diet therapy*
  • Diabetes Mellitus, Type 2 / genetics
  • Disease Models, Animal
  • Glucose Clamp Technique
  • Histocytochemistry
  • Hypertriglyceridemia / blood
  • Hypertriglyceridemia / diet therapy
  • Hypertriglyceridemia / genetics
  • Insulin / blood
  • Lipoprotein Lipase / blood
  • Liver / metabolism
  • Liver / pathology
  • Male
  • Muscle, Skeletal / metabolism
  • Organ Size
  • Pancreas / metabolism
  • Pancreas / pathology
  • Rats
  • Rats, Inbred OLETF
  • Rats, Long-Evans
  • Triglycerides / blood*


  • Blood Glucose
  • Insulin
  • Triglycerides
  • Lipoprotein Lipase