Abstract
There are substantial shortcomings in the drugs currently available for treatment of type 2 diabetes mellitus. The global diabetic crisis has not abated despite the introduction of new types of drugs and targets. Persistent unaddressed patient needs remain a significant factor in the quest for new leads in routine studies. Drug discovery methods in this area have followed developments in the market, contributing to a recent rise in the number of molecules. Nevertheless, troubling developments and fresh challenges are still evident. Recently, metformin, the most widely used first-line drug for diabetes, was found to contain a carcinogenic contaminant known as N-nitroso dimethylamine (NDMA). Therefore, purity and toxicity are also a big challenge for drug discovery and development. Moreover, newer drug classes against SGLT-2 illustrate both progress and difficulties. The same was true previously in the case of glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors. Furthermore, researchers must study the importance of mechanistic characteristics of novel compounds, as well as exposure-related hazardous aspects of current and newly identified protein targets, in order to identify new pharmacological molecules with improved selectivity and specificity.
Highlights
University Institute of Pharmaceutical Sciences, UGC Centre for Advanced Studies, Panjab University, Department of Nuclear Medicine, Manipal College of Health Professions (MCHP), Manipal Academy of Chitkara University Institute of Engineering and Technology, Chitkara University, Rajpura 140401, India; Department of Pharmacology, New York Medical College, Valhalla, NY 10595, USA
protein tyrosine phosphatase 1B (PTP1B) dephosphorylates phosphor-tyrosine residues of insulin receptor kinase activation segments leading to negative regulation of insulin signaling
Fernandez-Ruiz et al found that that PTP1B knockout mice have a higher proliferation of β-cells and elevated glucose-induced insulin secretion [27]
Summary
The first reference to diabetes was in 1550 B.C. in an Egyptian papyrus, where it was described as a rare disease characterized by excessive weight loss and frequent urination [8]. The sweet taste of a diabetic patient’s urine apparently led to its second name, mellitus Later in the 19th century, Matthew Dobson discovered that the excessive amount of sugar in the urine of patients with diabetes gives it that sweet taste. He provided an important distinction between the two different types of diabetes, which are referred to as type 1 and type 2 diabetes. The detailed classification can be found in the WHO’s classification of diabetes mellitus 2019 [12]
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