The Role of Beta Cell Recovery in Type 2 Diabetes Remission

Abstract

Type 2 diabetes (T2D) has been considered a relentlessly worsening disease, due to the progressive deterioration of the pancreatic beta cell functional mass. Recent evidence indicates, however, that remission of T2D may occur in variable proportions of patients after specific treatments that are associated with recovery of beta cell function. Here we review the available information on the recovery of beta cells in (a) non-diabetic individuals previously exposed to metabolic stress; (b) T2D patients following low-calorie diets, pharmacological therapies or bariatric surgery; (c) human islets isolated from non-diabetic organ donors that recover from "lipo-glucotoxic" conditions; and (d) human islets isolated from T2D organ donors and exposed to specific treatments. The improvement of insulin secretion reported by these studies and the associated molecular traits unveil the possibility to promote T2D remission by directly targeting pancreatic beta cells.

Keywords: bariatric surgery; glucotoxicity; insulin secretion; lipotoxicity; low-calorie diets; pancreatic beta cells; pancreatic islets; remission; transcriptome; type 2 diabetes.

Figure 1

Simplified trajectory of beta cell damage in type 2 diabetes. Obesity and the associated insulin resistance lead to beta cell overwork and the resulting hyperinsulinemia maintains blood glucose levels within the normal range. In case of genetic predisposition, metabolic stress, inflammation and other factors cause alterations in key beta cell organelles, which contributes to beta cell dysfunction and/or death. ER, endoplasmic reticulum.