<p>A Recent Achievement In the Discovery and Development of Novel Targets for the Treatment of Type-2 Diabetes Mellitus</p>

Abstract

Type 2 diabetes (T2DM) is a chronic metabolic disorder. Impaired insulin secretion, enhanced hepatic glucose production, and suppressed peripheral glucose use are the main defects responsible for developing the disease. Besides, the pathophysiology of T2DM also includes enhanced glucagon secretion, decreased incretin secretion, increased renal glucose reabsorption, and adipocyte, and brain insulin resistance. The increasing prevalence of T2DM in the world beseeches an urgent need for better treatment options. The antidiabetic drugs focus on control of blood glucose concentration, but the future treatment goal is to delay disease progression and treatment failure, which causes poorer glycemic regulation. Recent treatment approaches target on several novel pathophysiological defects present in T2DM. Some of the promising novel targets being under clinical development include those that increase insulin sensitization (antagonists of glucocorticoids receptor), decreasing hepatic glucose production (glucagon receptor antagonist, inhibitors of glycogen phosphorylase and fructose-1,6-biphosphatase). This review summarizes studies that are available on novel targets being studied to treat T2DM with an emphasis on the small molecule drug design. The experience gathered from earlier studies and knowledge of T2DM pathways can guide the anti-diabetic drug development toward the discovery of drugs essential to treat T2DM.

Lysophosphatidylcholine Containing Anisic Acid Is Able to Stimulate Insulin Secretion Targeting G Protein Coupled Receptors

“…Other oral glucose-lowering medications such as sulfonylureas and meglitinide analogues acting directly on the islet β cells to close ATP-sensitive potassium channels and stimulate insulin secretion, acarbose, and miglitol, being α-glucosidase inhibitors which interfere with gut glucose production or amylin analogues suppressing glucagon release, are not commonly used. Furthermore, the guidelines emphasize the importance of individualizing the choice of medications, considering comorbidities, patient preferences, side effects, and cost [2][3][4].…”

“…MIN6 cells viability after 24-h (a) and 48-h (b) treatment in fasting conditions with p-anisic acid (1), phosphatidylcholines substituted with at anisic and/or palmitoyl acyl residues in different configurations(4)(5)(6), and 1-anisoyl-lysophosphatidylcholine (LPC) (7) in the range of 5-500 μM concentrations. The viability is expressed as % of viable cells after treatment with respective quantities of the compound solvent (EtOH/DMSO).…”

Beneficial effect of anti-diabetic drugs for nonalcoholic fatty liver disease

“…Protein tyrosine phosphatase 1B inhibitor, free fatty acid receptors 1, aldose reductase, glycogen phosphorylase, fructose-1, 6-bisphosphatase, glucagon receptor antagonist, and phosphoenolpyruvate carboxykinase are currently being assessed. 103 Among them, drugs that show weight reduction can be effective in the treatment of NAFLD. Further studies are warranted to evaluate the efficacy of novel anti-diabetic drugs for NAFLD.…”

Direct Effects of D-Chiro-Inositol on Insulin Signaling and Glucagon Secretion of Pancreatic Alpha Cells

“…Although glucagon dysregulation is as important as insulin dysregulation in type 2 diabetes, therapeutic pharmacological approaches targeting glucagon are lacking [ 11 , 12 ], compared with pharmacological approaches that improve insulin secretion and β-cell function [ 13 , 14 ]. Furthermore, it is still unclear if specific treatments capable of improving the insulin sensitivity of pancreatic α-cells can also control glucagon levels in patients with diabetes mellitus.…”