Pharmacological inhibitors of β-cell dysfunction and death as therapeutics for diabetes

Abstract

More than 500 million adults suffer from diabetes worldwide, and this number is constantly increasing. Diabetes causes 5 million deaths per year and huge healthcare costs per year. β-cell death is the major cause of type 1 diabetes. β-cell secretory dysfunction plays a key role in the development of type 2 diabetes. A loss of β-cell mass due to apoptotic death has also been proposed as critical for the pathogenesis of type 2 diabetes. Death of β-cells is caused by multiple factors including pro-inflammatory cytokines, chronic hyperglycemia (glucotoxicity), certain fatty acids at high concentrations (lipotoxicity), reactive oxygen species, endoplasmic reticulum stress, and islet amyloid deposits. Unfortunately, none of the currently available antidiabetic drugs favor the maintenance of endogenous β-cell functional mass, indicating an unmet medical need. Here, we comprehensively review over the last ten years the investigation and identification of molecules of pharmacological interest for protecting β-cells against dysfunction and apoptotic death which could pave the way for the development of innovative therapies for diabetes.

Preservation of β-Cells as a Therapeutic Strategy for Diabetes

“…Chronic exposure of β-cells to hyperglycemia and elevated saturated fatty acids leads to glucotoxicity and lipotoxicity, contributing to β-cell dysfunction and apoptosis [54,55]. Chronic exposure to high glucose increases reactive oxygen species (ROS) formation, contributing to β-cell damage [56].…”

Novel lipid mediator 7S,14R-docosahexaenoic acid: biogenesis and harnessing mesenchymal stem cells to ameliorate diabetic mellitus and retinal pericyte loss

“…Hypoglycemic agents can significantly reduce the development of diabetic complications (1998; Want, 2008 ; Group et al, 2022 ); however, many of them cause adverse effects and sometimes result in progressive deterioration in β-cell function ( Efanova et al, 1998 ; Hakobyan et al, 2011 ; Dalle et al, 2023 ). Recently, some strategies using antioxidative treatment have been shown to ameliorate diabetic mellitus.…”

Novel Lipid Mediator <em>7S,14R</em>-Docosahexaenoic Acid: Biogenesis and Harnessing Mesenchymal Stem Cells to Ameliorate Diabetic Mellitus and Retinal Pericyte Loss

“…Hypoglycemic agents can significantly reduce the development of diabetic complications Want, 2008;Group et al, 2022); however, many of them cause adverse effects and sometimes result in progressive deterioration in β-cell function (Efanova et al, 1998;Hakobyan et al, 2011;Dalle et al, 2023). Recently, some strategies using antioxidative treatment have been shown to ameliorate diabetic mellitus.…”