Department of Medicine, Division of Diabetes, Endocrinology and Metabolism, Vanderbilt University School of Medicine, Nashville, TN 37232-0475, USA.
Postgrad Med. 2011 Jul;123(4):27-37. doi: 10.3810/pgm.2011.07.2301.
Insulin is a pleiotropic hormone with numerous effects at the cellular, tissue, and organismal levels. Clinicians are familiar with physiological effects of insulin on carbohydrate metabolism, including stimulation of glucose uptake in skeletal muscle and the suppression of glucose production from the liver. Other metabolic effects of insulin include inhibiting the release of free fatty acids from adipose tissue and stimulating the incorporation of amino acids into proteins. Indeed, every organ in the body, including the brain, is a target for insulin action. Insulin resistance, typically defined with respect to glucose metabolism, is a condition in which normal levels of insulin do not trigger the signal for glucose disposition. The effects of insulin resistance and impaired insulin signaling have profound pathophysiologic effects, such as hyperglycemia-induced tissue damage, hypertension, dyslipidemia, metabolic syndrome, and cardiovascular and renal disease. An integrated view of insulin action in all of these tissues may yield improved therapeutic insight and possibly even illuminate new therapeutic opportunities. With the increase in the number of patients diagnosed with prediabetes and diabetes, an updated understanding of the disease and the pharmacologic armamentarium used to treat it is needed to improve outcomes. To help expand the clinical care provider's perspective, this article will provide a provocative discussion about the pathophysiology of diabetes, the role of insulin and insulin resistance, and the clinical efficacy potential of insulin. Understanding the cellular and molecular mechanisms underlying the effects of insulin and how these translate into clinical consequences beyond glycemia will assist primary care physicians in the care of their patients with diabetes and metabolic syndrome.
胰岛素是一种具有多种细胞、组织和器官水平作用的多效激素。临床医生熟悉胰岛素对碳水化合物代谢的生理作用，包括刺激骨骼肌摄取葡萄糖和抑制肝脏葡萄糖产生。胰岛素的其他代谢作用包括抑制脂肪组织释放游离脂肪酸和刺激氨基酸掺入蛋白质。事实上，身体的每一个器官，包括大脑，都是胰岛素作用的靶标。胰岛素抵抗通常是指葡萄糖代谢方面的一种情况，即正常水平的胰岛素不能引发葡萄糖处置的信号。胰岛素抵抗和胰岛素信号受损的影响具有深远的病理生理效应，如高血糖引起的组织损伤、高血压、血脂异常、代谢综合征以及心血管和肾脏疾病。对所有这些组织中胰岛素作用的综合观点可能会产生改善治疗的见解，甚至可能阐明新的治疗机会。随着被诊断患有前驱糖尿病和糖尿病的患者数量的增加，需要更新对该疾病的认识以及用于治疗该疾病的药物武器库，以改善治疗效果。为了帮助扩大临床护理提供者的视角，本文将对糖尿病的病理生理学、胰岛素和胰岛素抵抗的作用以及胰岛素的临床疗效潜力进行有启发性的讨论。了解胰岛素作用的细胞和分子机制以及这些机制如何转化为血糖以外的临床后果，将有助于初级保健医生治疗糖尿病和代谢综合征患者。
