Department of Emergency and Organ Transplantation, Section of Internal Medicine, Endocrinology, Andrology and Metabolic Diseases, University of Bari Aldo Moro, 70124 Bari, Italy.
Int J Mol Sci. 2019 Feb 11;20(3):759. doi: 10.3390/ijms20030759.
Insulin is a major endocrine hormone also involved in the regulation of energy and lipid metabolism via the activation of an intracellular signaling cascade involving the insulin receptor (INSR), insulin receptor substrate (IRS) proteins, phosphoinositol 3-kinase (PI3K) and protein kinase B (AKT). Specifically, insulin regulates several aspects of the development and function of adipose tissue and stimulates the differentiation program of adipose cells. Insulin can activate its responses in adipose tissue through two INSR splicing variants: INSR-A, which is predominantly expressed in mesenchymal and less-differentiated cells and mainly linked to cell proliferation, and INSR-B, which is more expressed in terminally differentiated cells and coupled to metabolic effects. Recent findings have revealed that different distributions of INSR and an altered INSR-A:INSR-B ratio may contribute to metabolic abnormalities during the onset of insulin resistance and the progression to type 2 diabetes. In this review, we discuss the role of insulin and the INSR in the development and endocrine activity of adipose tissue and the pharmacological implications for the management of obesity and type 2 diabetes.
胰岛素是一种主要的内分泌激素，也通过激活涉及胰岛素受体 (INSR)、胰岛素受体底物 (IRS) 蛋白、磷酸肌醇 3-激酶 (PI3K) 和蛋白激酶 B (AKT) 的细胞内信号级联反应来调节能量和脂质代谢。具体而言，胰岛素调节脂肪组织的发育和功能的几个方面，并刺激脂肪细胞的分化程序。胰岛素可以通过两种 INSR 剪接变体在脂肪组织中激活其反应：主要在间充质和分化程度较低的细胞中表达且主要与细胞增殖相关的 INSR-A，以及在终末分化细胞中表达更多且与代谢作用相关的 INSR-B。最近的研究结果表明，INSR 的不同分布和 INSR-A:INSR-B 比值的改变可能导致胰岛素抵抗发生和 2 型糖尿病进展期间代谢异常。在这篇综述中，我们讨论了胰岛素和 INSR 在脂肪组织的发育和内分泌活性中的作用，以及在肥胖症和 2 型糖尿病管理中的药理学意义。
