Clofibrate enhances the affinity of insulin receptors in non‐insulin dependent diabetes mellitus.

Abstract

Glucose-lowering mechanism by clofibrate was studied in non-insulin dependent diabetics managed with dietary therapy alone. Clofibrate 1500 mg was administered for 1 month to 15 patients, and 75 g oral glucose tolerance test and insulin tolerance test were carried out before and after 1 month of the treatment. Fasting plasma glucose values were decreased from 9.34 + 0.53 mmol/l to 7.58 ± 0.33 mmol/l (P < 0.01), and fasting insulin levels were decreased from 13.8 ± 1.7 ,uu/ml to 10.1 + 1.5 5,u/ml (P < 0.05). However, insulinogenic index and 2IRI/Eglucose ratio during 75 g oral glucose tolerance test were not changed. Enhanced glucose fall in insulin tolerance test was also observed. As these results suggested the enhanced tissue sensitivity to insulin, we examined the insulin binding to erythrocytes before and at 3 months' treatment of clofibrate in 10 non-insulin dependent diabetics. Insulin bindings were increased from 3.41 ± 0.17% to 4.11 + 0.20% in the presence of 1 ng/ml of native insulin (P < 0.01). This increased binding was due to an increased affinity without a change in the number of insulin receptors. These results suggest that improved glucose tolerance by clofibrate might be derived from the enhanced tissue sensitivity to insulin, probably through an enhanced affinity of insulin receptors.

Improvement of Glucose Tolerance in NIDDM by Clofibrate Randomized Double-Blind Study

“…Increased affinity of insulin receptors has been reported (11). We tested 10 subjects before and after either placebo or treatment with clofi- brate.…”

Sorting out the roles of PPAR in energy metabolism and vascular homeostasis

“…This suggests that PPARα activation in skeletal muscles shifts substrate utilization from glucose to FA, a conclusion supported by loss-of-function experiments (73,83). However, only a few clinical trials report an improvement of glucose homeostasis after fibrate treatment (84)(85)(86)(87). Moreover, the recent Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study did not reveal any effect of fenofibrate on glucose parameters in diabetic patients (88); this suggests that effects on glucose homeostasis may be species specific.…”

Peroxisome Proliferator-Activated Receptors and Caloric Restriction—Common Pathways Affecting Metabolism, Health, and Longevity

“…Fasting plasma glucose, oral glucose tolerance test results, and immunoreactive insulin in these patients are significantly decreased, which is accompanied by enhanced glucose use and decreased serum TGs and cholesterol [ 371 ]. Furthermore, clofibrate in patients with non-insulin-dependent diabetes decreases fasting plasma glucose and insulin levels, and insulin binding to erythrocytes is enhanced because of increased insulin receptor affinity without a change in receptor number [ 372 ]. Another study showed that clofibrate ameliorates glucose tolerance in this patient population without changing the number of insulin receptors and that this increased insulin sensitivity occurs via an unknown post-receptor mechanism [ 373 ].…”