Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

While glycemic control remains the cornerstone of clinical management for patients with type 2 diabetes, the importance of a more comprehensive approach that addresses the multiple metabolic abnormalities seen in this population is now widely recognized. Abnormal lipid metabolism resulting in dyslipidemia contributes greatly to the markedly increased risks of cardiovascular disease observed in diabetic patients and in prediabetic patients with signs of insulin resistance. The peroxisome proliferator-activated receptors (PPARs) play a key role in the regulation of energy homeostasis and the coordination of inflammatory responses. As such, they are interesting targets for addressing both the glucose and lipid abnormalities associated with insulin resistance. The thiazolidinediones (TZDs), which activate PPARgamma, appear to improve glycemic control primarily by increasing peripheral insulin sensitivity and reducing hepatic glucose production, thereby helping to preserve beta-cell function. They have also demonstrated modest beneficial effects on some lipid parameters. The fibrate drugs, which activate PPARalpha, produce robust improvements in dyslipidemia, decrease atherosclerotic lesions and may have an effect on cardiovascular events, but do not affect glycemia. Theoretically, a compound targeting both the alpha and gamma PPARs simultaneously might combine the benefits of TZDs and fibrates. Tesaglitazar is a dual-acting PPARalpha/gamma agonist currently being investigated in phase III clinical trials as an alternative treatment for insulin resistance and the characteristic dyslypidemia of type 2 diabetes. This article reviews the available data on the clinical efficacy and safety of tesaglitazar in patients with type 2 diabetes and in individuals without diabetes but with insulin resistance.
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PMID:Tesaglitazar: a promising approach in type 2 diabetes. 1662 56

Metabolic syndrome increases the risk of developing diabetes as well as cardiovascular and kidney diseases. This research studied the effects of tesaglitazar, a dual-acting peroxisome proliferator-activated receptor (PPAR)alpha/gamma agonist, on metabolic abnormalities and kidney injury in obese Zucker rats (OZR). Lean Zucker rats (LZR) and OZR were used as control groups. Tesaglitazar (1 micromol/kg/day) was given for 8 weeks in the treatment group (OZR-T). Metabolic parameters, 24-hour urine albumin excretion, and tail blood pressure were measured. Glomerular filtration rate by inulin clearance, abdominal fat and renal histology were determined at the end of the study. In comparison with the OZR and OZR-T groups, the LZR control animals' parameters were significantly more favorable in all measures. Tesaglitazar treatment in OZR significantly reduced nonfasting glucose, C-reactive protein levels and improved dyslipidemia. Body weight, blood pressure and urine albumin excretion were lower, but the adjusted glomerular filtration rate higher, in the OZR-T group than in the OZR controls. Glomerular area, mesangial expansion and tubulointerstitial changes were ameliorated, and the glomerular expression of desmin was markedly more decreased in the OZR-T group than in the OZR controls. Therefore, the PPAR alpha/gamma agonist tesaglitazar significantly improved metabolic abnormalities and renal function, decreased blood pressure, and protected against glomerular and interstitial damage in OZR.
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PMID:Tesaglitazar, a dual peroxisome proliferator-activated receptor agonist (PPAR alpha/gamma), improves metabolic abnormalities and reduces renal injury in obese Zucker rats. 1988 47