Peroxisome Proliferator-Activated Receptor (PPAR) in Metabolic Syndrome and Type 2 Diabetes Mellitus
Peroxisome Proliferator-Activated Receptor (PPAR) in Metabolic Syndrome and Type 2 Diabetes Mellitus
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DOI：
10.2174/157339907779802067
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发表时间：
2007-01-01
影响因子：
3.3
通讯作者：
Ren, Jun
中科院分区：
文献类型：
--
作者：
Jay, Mollie A.;Ren, Jun
2型糖尿病是一种全球性流行病，很大程度上归因于代谢综合征及其一系列心血管危险因素，包括腹部肥胖、血脂异常、高血压和高血糖。最佳控制与代谢综合征相关危险因素的两种主要方法是改变生活方式和药物治疗。尽管已经确定了许多药理学靶点，但与代谢综合征和 2 型糖尿病相关的心血管危险因素的临床管理仍然令人沮丧。最近的证据表明，过氧化物酶体增殖物激活受体 (PPAR) 配体可以对抗 2 型糖尿病和代谢综合征，包括肥胖和胰岛素抵抗。已鉴定出 PPAR 核脂肪酸受体的三种亚型：β/δ 和 γ PPAR 被认为主要参与肝脏和心脏的脂肪酸摄取（β 和 omega 氧化）。 PPAR γ 参与肌肉中的脂肪酸氧化。 PPAR 在脂肪中高表达，可促进葡萄糖和脂质的摄取、刺激葡萄糖氧化、降低游离脂肪酸水平并改善胰岛素抵抗。 PPAR α 和 γ 的合成配体（例如纤维酸和噻唑烷二酮）已用于治疗 2 型糖尿病和糖尿病前期胰岛素抵抗患者，可显着改善 HbA(1c) 和血糖水平。此外，PPAR激动剂或双重激动剂可能会引起非降血糖作用，包括改善脂质代谢、血压控制和内皮功能，以及抑制动脉粥样硬化斑块形成和凝血。然而，使用 PPAR 激动剂降低代谢综合征和 2 型糖尿病心脏病发病率的安全性和临床适应症问题仍未确定。
Type 2 diabetes mellitus, a global epidemic, is largely attributed to metabolic syndrome and its clustering of cardiovascular risk factors including abdominal obesity, dyslipidemia, hypertension and hyperglycemia. The two primary approaches to optimally control risk factors associated with metabolic syndrome are lifestyle changes and medications. Although many pharmacological targets have been identified, clinical management of cardiovascular risk factors associated with metabolic syndrome and type 2 diabetes is still dismal. Recent evidence suggests premises of the peroxisome proliferator-activated receptor (PPAR) ligands in the combat against type 2 diabetes and metabolic syndrome including obesity and insulin resistance. Three subtypes of the PPAR nuclear fatty acid receptors have been identified:, beta/delta and gamma PPAR is believed to participate in fatty acid uptake (beta- and omega-oxidation) mainly in the liver and heart. PPAR gamma is involved in fatty acid oxidation in muscle. PPAR is highly expressed in fat to facilitate glucose and lipid uptake, stimulate glucose oxidation, decrease free fatty acid level and ameliorate insulin resistance. Synthetic ligands for PPAR alpha and gamma such as fibric acid and thiazolidinediones have been used in patients with type 2 diabetes and pre-diabetic insulin resistance with significantly improved HbA(1c) and glucose levels. In addition, nonhypoglycemic effects may be elicited by PPAR agonists or dual agonists including improved lipid metabolism, blood pressure control and endothelial function, as well as suppressed atherosclerotic plaque formation and coagulation. However, issues of safety and clinical indication remain undetermined for use of PPAR agonists for the incidence of heart disease in metabolic syndrome and type 2 diabetes.