Sabir Shakila, Saleem Ammara, Akhtar Muhammad Furqan, Saleem Muhammad, Raza Moosa
Faculty of Pharmaceutical Sciences, Government College University Faisalabad, Pakistan.
Faculty of Pharmacy, University of Lahore, Lahore, Pakistan.
Adv Clin Exp Med. 2018 Sep;27(9):1309-1315. doi: 10.17219/acem/74452.
Finding a radical cure for diabetes has reached paramount importance in medicine due to the widespread prevalence of the disease. A substantial reduction in insulin-secreting beta cells is evident in diabetes. The failure of cyclin-dependent kinases (CDKs) and cyclins to access the nucleus is responsible for quiescence or senescence in human and rodent beta cells. The augmentation of beta cell proliferation is supposed to reverse diabetes. This concept has inspired the discovery of newer drugs that encourage the proliferation of beta cells. Although it is a rational step towards a cure for diabetes, the differences in biochemical pathways in rodents and human beta cells pose difficulty in promoting the proliferation of human beta cells. Primarily, it is mandatory to clearly understand the intracellular pathways involved in the proliferation of beta cells so as to pave the way for therapeutic interventions. There are several intrinsic factors that trigger the proliferation of beta cells. Furthermore, it is also obvious that the early death of beta cells due to oxidative stress-related upregulation of pro-apoptotic genes also predisposes individuals to diabetes mellitus. Polyphenols, exendin 4, histone deacetylase inhibitors, glucagon-like peptide 1, phenyl pyruvic acid glucoside, and several flavonoids reduce the early apoptosis of beta cells partly through their role in the reduction of oxidative stress. A better understanding of intracellular pathways, the identification of specific mitogens, the induction of beta cell proliferation, and the inhibition of apoptosis may help us treat diabetes mellitus through an increase in beta cell mass.
由于糖尿病的广泛流行，找到一种根治糖尿病的方法在医学上已变得至关重要。在糖尿病中，胰岛素分泌β细胞大量减少是显而易见的。细胞周期蛋白依赖性激酶（CDK）和细胞周期蛋白无法进入细胞核是导致人类和啮齿动物β细胞静止或衰老的原因。β细胞增殖的增加有望逆转糖尿病。这一概念激发了人们发现鼓励β细胞增殖的新药。尽管这是朝着治愈糖尿病迈出的合理一步，但啮齿动物和人类β细胞生化途径的差异给促进人类β细胞增殖带来了困难。首先，必须清楚了解β细胞增殖所涉及的细胞内途径，以便为治疗干预铺平道路。有几种内在因素会触发β细胞的增殖。此外，由于促凋亡基因的氧化应激相关上调导致β细胞过早死亡，这也使个体易患糖尿病。多酚、艾塞那肽4、组蛋白去乙酰化酶抑制剂、胰高血糖素样肽1、苯丙酮酸葡萄糖苷和几种黄酮类化合物部分通过减少氧化应激的作用来减少β细胞的早期凋亡。更好地理解细胞内途径、识别特定的促有丝分裂原、诱导β细胞增殖以及抑制细胞凋亡可能有助于我们通过增加β细胞数量来治疗糖尿病。
