Montecucco Fabrizio, Steffens Sabine, Mach François
Division of Cardiology, Foundation for Medical Researches, University Hospital, 1211 Geneva, Switzerland.
Mediators Inflamm. 2008;2008:767623. doi: 10.1155/2008/767623.
The dysregulation of the insulin-glucose axis represents the crucial event in insulin resistance syndrome. Insulin resistance increases atherogenesis and atherosclerotic plaque instability by inducing proinflammatory activities on vascular and immune cells. This condition characterizes several diseases, such as type 2 diabetes, impaired glucose tolerance (IGT), impaired fasting glucose (IFG), obesity, hypertension, dyslipidemia, and other endocrinopathies, but also cancer. Recent studies suggest that the pathophysiology of insulin resistance is closely related to interferences with insulin-mediated intracellular signaling on skeletal muscle cells, hepatocytes, and adipocytes. Strong evidence supports the role of free fatty acids (FFAs) in promoting insulin resistance. The FFA-induced activation of protein kinase C (PKC) delta, inhibitor kappaB kinase (IKK), or c-Jun N-terminal kinase (JNK) modulates insulin-triggered intracellular pathway (classically known as PI3-K-dependent). Therefore, reduction of FFA levels represents a selective target for modulating insulin resistance.
胰岛素 - 葡萄糖轴的失调是胰岛素抵抗综合征中的关键事件。胰岛素抵抗通过诱导血管和免疫细胞的促炎活性，增加动脉粥样硬化的发生和动脉粥样硬化斑块的不稳定性。这种情况是多种疾病的特征，如2型糖尿病、糖耐量受损（IGT）、空腹血糖受损（IFG）、肥胖、高血压、血脂异常以及其他内分泌疾病，还包括癌症。最近的研究表明，胰岛素抵抗的病理生理学与骨骼肌细胞、肝细胞和脂肪细胞上胰岛素介导的细胞内信号传导受到干扰密切相关。有力证据支持游离脂肪酸（FFA）在促进胰岛素抵抗中的作用。FFA诱导的蛋白激酶C（PKC）δ、抑制蛋白κB激酶（IKK）或c - Jun氨基末端激酶（JNK）的激活，调节胰岛素触发的细胞内途径（经典上称为PI3 - K依赖性途径）。因此，降低FFA水平是调节胰岛素抵抗的一个选择性靶点。
