Research & Development, Lovely Professional University, Phagwara, Punjab-144411, India.
Center for Molecular Biology, Institute of Research and Development, Duy Tan University, 03 Quang Trung, Da Nang, Vietnam.
Curr Pharm Des. 2019;25(23):2526-2539. doi: 10.2174/1381612825666190716102901.
Diabetes is one of the most common endocrine non-communicable metabolic disorders which is mainly caused either due to insufficient insulin or inefficient insulin or both together and is characterized by hyperglycemia. Diabetes emerged as a serious health issue in the industrialized and developing country especially in the Asian pacific region. Out of the two major categories of diabetes mellitus, type 2 diabetes is more prevalent, almost 90 to 95% cases, and the main cause of this is insulin resistance. The main cause of the progression of type 2 diabetes mellitus has been found to be insulin resistance. The type 2 diabetes mellitus may be managed by the change in lifestyle, physical activities, dietary modifications and medications. The major currently available management strategies are sulfonylureas, biguanides, thiazolidinediones, α-glucosidase inhibitors, dipeptidyl peptidase-IV inhibitors, and glucagon-like peptide-1 (GLP-1) agonist. Binding of insulin on the extracellular unit of insulin receptor sparks tyrosine kinase of the insulin receptor which induces autophosphorylation. The phosphorylation of the tyrosine is regulated by insulin and leptin molecules. Protein tyrosine phosphatase-1B (PTP1B) works as a negative governor for the insulin signalling pathways, as it dephosphorylates the tyrosine of the insulin receptor and suppresses the insulin signalling cascade. The compounds or molecules which inhibit the negative regulation of PTP1B can have an inductive effect on the insulin pathway and finally help in the management of diabetes mellitus. PTP1B could be an emerging therapeutic strategy for diabetes management. There are a number of clinical and basic research results which suggest that induced expression of PTP1B reduces insulin resistance. In this review, we briefly elaborate and explain the place of PTP1B and its significance in diabetes as well as a recent development in the PTP1B inhibitors as an antidiabetic therapy.
糖尿病是最常见的内分泌代谢紊乱性非传染性疾病之一，主要是由于胰岛素不足或胰岛素作用效率低下（或两者兼有）引起的，其特征是高血糖。糖尿病已成为工业化国家和发展中国家（特别是亚太地区）的一个严重健康问题。在两种主要类型的糖尿病中，2 型糖尿病更为普遍，约占 90%至 95%，其主要原因是胰岛素抵抗。2 型糖尿病进展的主要原因已被发现是胰岛素抵抗。2 型糖尿病可以通过改变生活方式、体育活动、饮食调整和药物治疗来控制。目前主要的管理策略有磺酰脲类、双胍类、噻唑烷二酮类、α-葡萄糖苷酶抑制剂、二肽基肽酶-IV 抑制剂和胰高血糖素样肽-1（GLP-1）激动剂。胰岛素与胰岛素受体细胞外单元结合会引发胰岛素受体的酪氨酸激酶，从而诱导自身磷酸化。酪氨酸的磷酸化受胰岛素和瘦素分子的调节。蛋白酪氨酸磷酸酶-1B（PTP1B）是胰岛素信号通路的负调控因子，因为它可以使胰岛素受体的酪氨酸去磷酸化，并抑制胰岛素信号级联反应。抑制 PTP1B 负调控的化合物或分子可以对胰岛素通路产生诱导作用，最终有助于糖尿病的管理。PTP1B 可能成为糖尿病管理的新兴治疗策略。有许多临床和基础研究结果表明，PTP1B 的诱导表达会降低胰岛素抵抗。在这篇综述中，我们简要阐述并解释了 PTP1B 的作用及其在糖尿病中的意义，以及作为抗糖尿病治疗的 PTP1B 抑制剂的最新进展。
