ABSTRACT
<p><b>AIM</b>To investigate the ameliorations of pioglitazone, a member of the thiazolidinedione group of antidiabetic agents, on insulin resistance in spontaneous OLETF rats with impaired glucose tolerance (IGT-OLETF).</p><p><b>METHODS</b>One group of IGT-OLETF rats was orally administered pioglitazone at the dose of 20 mg x kg(-1) (qd) for 2 weeks. Another group was given the same volume of solvent as control. Glucose tolerance and insulin tolerance were tested, and blood glucose concentrations, insulin levels and lipids in serum, liver and muscle were determined. Insulin sensitive index (ISI) was calculated by the reciprocal of fasting blood glucose times fasting insulin.</p><p><b>RESULTS</b>Pioglitazone was shown to markedly enhance the glycemic response to exogenous insulin (0. 4 x kg(-1), sc) in the model. The falls of blood glucose at 40 and 90 min in the insulin tolerance test were augmented by 70% and 158% in the treated group than the control. The serum insulin levels were significantly decreased and the ISI nearly normalized after treatment. Pioglitazone also lowered the serum TG and FFA levels and the lipids in liver and muscle. No effect was found on the expression of leptin in epididymal adipose tissues and on the activity of GFAT, a key enzyme in hexosamine biosynthesis pathway (data were not shown).</p><p><b>CONCLUSION</b>Pioglitazone can improve the insulin resistance state in IGT-OLETF rats. Correction of lipid disorder may be associated with it.</p>
Subject(s)
Animals , Male , Rats , Blood Glucose , Metabolism , Cholesterol , Blood , Cholesterol, HDL , Blood , Cholesterol, LDL , Blood , Diabetes Mellitus, Type 2 , Metabolism , Fatty Acids, Nonesterified , Blood , Metabolism , Glucose Tolerance Test , Hypoglycemic Agents , Pharmacology , Insulin , Metabolism , Insulin Resistance , Liver , Metabolism , Rats, Inbred OLETF , Rats, Wistar , Thiazolidinediones , Pharmacology , Triglycerides , Blood , MetabolismABSTRACT
<p><b>AIM</b>To study the effect of conjugated linoleic acid (CLA) on obese MSG mice with insulin resistance.</p><p><b>METHODS</b>About four months old, obese MSG mice with insulin resistance were divided into control, CLA and rosiglitazone groups and drugs were administrated ig once a day. Body weights were recorded regularly, insulin and glucose tolerance were tested. In addition, serum insulin and TNF-alpha concentrations in serum and fat tissues were determined.</p><p><b>RESULTS</b>CLA was shown to reduce the body weight and fat weight in MSG mice, but can not improve the abnormal insulin and glucose tolerance in these mice. Indeed, the serum insulin and TNF-alpha concentrations in the fat tissues of the group treated with CLA were higher than those in the models and the insulin sensitivity index was significantly lower than that in the model mice.</p><p><b>CONCLUSION</b>CLA can reduce the body weight of MSG mice, but can not improve the insulin resistance in these mice.</p>
Subject(s)
Animals , Female , Male , Mice , Adipose Tissue , Metabolism , Animals, Newborn , Blood Glucose , Metabolism , Body Weight , Glucose Tolerance Test , Insulin , Blood , Insulin Resistance , Linoleic Acids, Conjugated , Pharmacology , Mice, Inbred ICR , Obesity , Metabolism , Sodium Glutamate , Tumor Necrosis Factor-alpha , MetabolismABSTRACT
Peroxisome proliferator activated receptor(PPAR), a member of the hormone receptor superfamily, is a key regulating factor in adipocyte differentiation and lipids metabolism. Recently, with the increased understanding of the precise mechanisms of TZD, thiazolidinedione class of insulin sensitizer, PPARγ has also been identified as the major functional receptor for the drugs. In the study of the relationship between PPAR and insulin resistance, considerable gaps appeared. TZD induced activation of PPARγ is known to promote insulin sensitivity. More interestingly, however, PPRAγ+/- heterozygous mice were shown to be less susceptible to insulin resistance. These findings suggest that the relationship between PPAR activation and insulin sensitivity improvement is not simplely positively related. A better understanding of the role of PPAR in insulin action system will be critical in developing more efficacious and safe agents that act on PPAR and benefit patients with type 2 diabetes.