Partners in Crime: Beta-Cells and Autoimmune Responses Complicit in Type 1 Diabetes Pathogenesis

Type 1 diabetes (T1D) is an autoimmune disease characterized by autoreactive T cell-mediated destruction of insulin-producing pancreatic beta-cells. Loss of beta-cells leads to insulin insufficiency and hyperglycemia, with patients eventually requiring lifelong insulin therapy to maintain normal glycemic control. Since T1D has been historically defined as a disease of immune system dysregulation, there has been little focus on the state and response of beta-cells and how they may also contribute to their own demise. Major hurdles to identifying a cure for T1D include a limited understanding of disease etiology and how functional and transcriptional beta-cell heterogeneity may be involved in disease progression. Recent studies indicate that the beta-cell response is not simply a passive aspect of T1D pathogenesis, but rather an interplay between the beta-cell and the immune system actively contributing to disease. Here, we comprehensively review the current literature describing beta-cell vulnerability, heterogeneity, and contributions to pathophysiology of T1D, how these responses are influenced by autoimmunity, and describe pathways that can potentially be exploited to delay T1D.

Molecular Mechanism of Corticosteroid-Induced Hyperglycemia

Corticosteroids are widely used as strong anti-inflammatory and immunosuppressive drugs to treat various diseases. However, the use of corticosteroids can cause several side effects, such as hyperglycemia. This review aims to examine the effect of corticosteroids on increasing glucose in molecular levels based on literature studies. A literature searching was carried out on the PubMed, Science Direct, and Google Scholar databases published in 2010-2020. Corticosteroids can cause an increase in blood glucose levels by several mechanisms. In the liver, glucocorticoids increase endogenous plasma glucose and stimulate gluconeogenesis. Glucocorticoids increase the production of non-esterified fatty acids which affect the signal transduction of insulin receptor substrate-1 in skeletal muscle. In adipose, glucocorticoids increase lipolysis and visceral adiposity through increased transcription and expression of protein adipose triglyceride lipase and hormone-sensitive lipase. In pancreatic beta cells, glucocorticoids directly inhibit the beta cell response to glucose through the role of protein kinase B and protein kinase C. At the molecular level, corticosteroids can cause hyperglycemia through mechanisms in the liver, skeletal muscle tissue, adipose tissue, and pancreatic beta cells.