Insulin resistance and impaired glucose tolerance in the atherosclerosis-prone LA/N corpulent rat.

Abstract

The LA/N-cp rat is, when homozygous for the cp gene, hyperphagous, hyperlipidemic, and corpulent. The corpulent males develop atherosclerotic disease and myocardial lesions while corpulent females and lean rats do not. The fasting plasma glucose concentrations of corpulent rats are in the normal range, but insulin concentrations are mildly elevated in corpulent females and markedly elevated in corpulent males. Glucose tolerance testing reveals a glucose intolerance in corpulent rats in the presence of very high insulin concentrations, and this deficiency is more severe in the male rats. Glucagon concentrations are higher in corpulent rats than lean rats at 3 months of age and decrease progressively with age. In contrast, glucagon concentrations increase with age in lean rats and are higher than those in corpulent rats at 9 months. The islets of Langerhans of corpulent rats exhibit marked hyperplasia that increases with age. The hyperplasia is less extreme in corpulent female rats. The abnormalities suggest that this strain of rats has an insulin resistance leading to impaired glucose tolerance and progressive pancreatic disturbance. This process may be related to an accompanying defect causing elevated concentrations of very low density lipoproteins and correlates with the development of atherosclerotic disease.

Nifedipine increases energy expenditure by increasing PGC-1α expression in skeletal muscle

“…The present study revealed that nonhypotensive doses of nifedipine (a dose of 1 mg kg À1 per day via infusion pump for 4 months) significantly reduced epididymal WAT and body weight gain, suggesting that the nifedipine has an antiobesity effect. In agreement, Russell et al 21,22 reported that nifedipine treatment (a dose of 15 mg kg À1 per day in food pellets for 7.5 months) moderately decreased the body weight of JCR:LA-cp/cp rats, a normotensive obese rat model with marked hyperlipidemia and insulin resistance, indicating that nifedipine directly affects weight loss. Iwai et al 17 also reported that non-hypotensive doses of nifedipine (average dose 1.5 mg kg À1 per day in lab chow for 5 weeks) significantly decreased epididymal WAT weight and moderately decreased wholebody weight of obese diabetic KK-A y mice by stimulating adipocyte differentiation.…”

Improvement of insulin sensitivity and cardiovascular outcomes in the JCR:LA-cp rat by D-fenfluramine

“…Male cp/cp rats, while highly insulin resistant and with impaired glucose tolerance, do not have fasting hyperglycaemia and are not diabetic [16]. Thus, dfenfluramine did not decrease fasting plasma glucose concentrations (Fig.…”

Effects of chronic ethanol consumption in atherosclerosis-prone JCR:LA-corpulent rat.

“…23 The rats exhibit an insulin resistance and impaired glucose tolerance, which like the myocardial lesions is more mild in the female corpulent rats than the males. 24 The vascular and myocardial lesions both develop only in cp/cp males, with lean and female rats being essentially unaffected. Both types of lesions increase in frequency with age.…”