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(searched for: doi:10.15415/jptrm.2019.72011)
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Preeti Gupta, Aaliya Taiyab,
Published: 24 November 2020
Structural and Mechanistic Enzymology, Volume 124, pp 47-85; https://doi.org/10.1016/bs.apcsb.2020.11.001

Abstract:
Diabetes mellitus has emerged as a severe burden on the medical health system across the globe. Presently, around 422 million people are suffering from diabetes which is speculated to be expanded to about 600 million by 2035. Patients with type 2 diabetes are at increased risk of developing detrimental metabolic and cardiovascular complications. The scientific understanding of this chronic disease and its underlying root cause is not yet fully unraveled. Protein kinases are well known to regulate almost every cellular process through phosphorylation of target protein in diverse signaling pathways. The important role of several protein kinases including AMP-activated protein kinase, IκB kinase and protein kinase C have been well demonstrated in various animal models. They modulate glucose tolerance, inflammation and insulin resistance in the cells via acting on diverse downstream targets and signaling pathways. Thus, modulating the activity of potential human kinases which are significantly involved in diabetes by targeting with small molecule inhibitors could be an attractive therapeutic strategy to tackle diabetes. In this chapter, we have discussed the potential role of protein kinases in glucose metabolism and insulin sensitivity, and in the pathogenesis of diabetes mellitus. Furthermore, the small molecules reported in the literature that can be potentially used for the treatment of diabetes have been discussed in detail.
Ying-Ying Zhu, Zu-Yao Yang, Ping Li, Xin-Ying Huang, Xue-Hong Zhang, Li-Nong Ji,
World Journal of Meta-Analysis, Volume 8, pp 400-409; https://doi.org/10.13105/wjma.v8.i5.400

Abstract:
Type 2 diabetes mellitus (T2DM) causes both macrovascular and microvascular complications. However, currently, selection of glycemic measures and their thresholds to diagnose T2DM, and efficacy outcomes in evaluation of anti-diabetic drugs is predominantly informed by the relation of T2DM to microvascular complications. We can be severely mistaken on T2DM by neglecting macrovascular complications which are generally more severe, if they also occur more commonly than microvascular complications. To compare the incidence of major cardiovascular events (MACEs) and severe microvascular complications (SMICs) in T2DM patients. MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials were searched from inception to September 2017. Cohort studies or trials of T2DM patients aged 18 years or older that reported incidence of both MACEs and SMICs were included. MACEs were defined as nonfatal myocardial infarction and stroke, and cardiovascular death, while SMICs included serious retinopathy, nephropathy and diabetic disorder. The relative risk (RR) was estimated as the incidence of MACEs divided by that of SMICs in same patients and combined with meta-analysis in a random-effect model. Twelve studies with a total of 16 cohorts and 387376 patients were included, and the combined RR was 2.02 (95%CI: 1.46–2.79). The higher incidence of MACEs remained in various subgroup and sensitivity analyses. Patients with T2DM are much more likely to develop MACEs than SMICs. By taking more serious consequences and relatively higher incidence into consideration, macrovascular complications deserve more emphasis in developing the diagnostic criteria of T2DM and in evaluating the efficacy of anti-diabetic drugs.
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