Emerging Anti-Diabetic Drugs for Beta-Cell Protection in Type 1 Diabetes.
Nida AjmalMaislin C BogartPalwasha KhanIbiagbani M Max-HarryCraig S NunemakerPublished in: Cells (2023)
Type 1 diabetes (T1D) is a chronic autoimmune disorder that damages beta cells in the pancreatic islets of Langerhans and results in hyperglycemia due to the loss of insulin. Exogenous insulin therapy can save lives but does not halt disease progression. Thus, an effective therapy may require beta-cell restoration and suppression of the autoimmune response. However, currently, there are no treatment options available that can halt T1D. Within the National Clinical Trial (NCT) database, a vast majority of over 3000 trials to treat T1D are devoted to insulin therapy. This review focuses on non-insulin pharmacological therapies. Many investigational new drugs fall under the category of immunomodulators, such as the recently FDA-approved CD-3 monoclonal antibody teplizumab. Four intriguing candidate drugs fall outside the category of immunomodulators, which are the focus of this review. Specifically, we discuss several non-immunomodulators that may have more direct action on beta cells, such as verapamil (a voltage-dependent calcium channel blocker), gamma aminobutyric acid (GABA, a major neurotransmitter with effects on beta cells), tauroursodeoxycholic acid (TUDCA, an endoplasmic reticulum chaperone), and volagidemab (a glucagon receptor antagonist). These emerging anti-diabetic drugs are expected to provide promising results in both beta-cell restoration and in suppressing cytokine-derived inflammation.
Keyphrases
- type diabetes
- induced apoptosis
- glycemic control
- cell cycle arrest
- single cell
- endoplasmic reticulum
- clinical trial
- cell therapy
- cardiovascular disease
- monoclonal antibody
- signaling pathway
- multiple sclerosis
- insulin resistance
- cell death
- oxidative stress
- emergency department
- metabolic syndrome
- endoplasmic reticulum stress
- skeletal muscle
- adipose tissue
- bone marrow
- replacement therapy
- cell proliferation
- wound healing