Beta-Cell Dysfunction Induced by Tacrolimus: A Way to Explain Type 2 Diabetes?

The combination of insulin resistance and beta-cells dysfunction leads to the onset of type-2 diabetes mellitus (T2DM). This process can last for decades, as beta-cells are able to compensate the demand for insulin and maintain normoglycemia. Understanding the adaptive capacity of beta-cells during this process and the causes of its failure is essential to the limit onset of diabetes. Post-transplant diabetes mellitus (PTDM) is a common and serious disease that affects 30% of renal transplant recipients. With the exception of immunosuppressive therapy, the risk factors for T2D are the same as for PTDM: obesity, dyslipidaemia, insulin resistance and metabolic syndrome. Tacrolimus (TAC) is the immunosuppressant of choice after renal transplantation but it has the highest rates of PTDM. Our group has shown that insulin resistance and glucolipotoxicity, without favouring the appearance of apoptosis, modify key nuclear factors for the maintenance of identity and functionality of beta-cells. In this context, TAC accelerates or enhances these changes. Our hypothesis is that the pathways that are affected in the progression from pre-diabetes to diabetes in the general population are the same pathways that are affected by TAC. So, TAC can be considered a tool to study the pathogenesis of T2DM. Here, we review the common pathways of beta-cells dysfunction on T2DM and TAC-induced diabetes.

Automated summary

This article discusses the mechanisms by which insulin resistance and beta-cell dysfunction lead to the onset of type-2 diabetes, as well as the similar pathways of diabetes induced by the immunosuppressant TAC.