Imeglimin to the Rescue: Enhanced CHOP/GADD34/eIF2 α Signaling Axis Promotes β-Cell Survival

Pancreatic β-cells are the main source of insulin in the body, and this hormone is required to maintain glucose homeostasis and normal metabolic health. Circulating insulin level is impacted by total β-cell mass in the pancreas, which is maintained by the ability of the β-cells to self-duplicate and survive from various stressors, such as apoptosis and endoplasmic reticulum (ER) stress. Given the inherently low rate of turnover in β-cells (1,2), apoptosis can play a key pathogenic role in the development of diabetes. While many factors contribute to the death of β-cells, such as inflammation and oxidative stress, ER homeostasis through the unfolded protein response (UPR) elements are of the utmost importance (3). As the insulin factory of the body, β-cells allocate a significant amount of energy on insulin synthesis in the ER, and the quantity of insulin produced is partly dependent on the processes that shape ER synthetic capacity (4). Current literature argues that induction of UPR in the face of ER stress represents a cell ’s functional adaptation to cellular stress, but, unchecked, it can ultimately cause the demise of a cell if the stressor is not remedied in a timely manner.

Source: Diabetes - February 23, 2022 Category: Endocrinology Source Type: research