Insulin release by human islet beta cells in the pancreas declines with age, which may contribute to the development of Type 2 diabetes.
By combining sophisticated gene expression profiling, high-resolution confocal microscopy and functional analysis, Rafael Arrojo e Drigo, PhD, and colleagues demonstrate that aging beta cells ramp up gene transcription and translation, while downregulating transcription factors essential for normal functioning of the beta cell and its endoplasmic reticulum (ER).
The ER is a cellular organelle that assembles and secretes proteins, including the hormone insulin, which transports glucose from the bloodstream into tissues. This study, published in the journal Science Advances, suggests that aging induces a chronic ER stress response in beta cells, resulting in decreased insulin secretion.
Drugs that stimulate receptors for the incretin GLP-1, an intestinal hormone, can reduce high blood glucose levels. Aging beta cells have higher expression of incretin receptors. Targeting incretin activity as one ages, therefore, may help preserve beta cell function by relieving ER stress, the researchers concluded.
Co-authors include first author Shristi Shrestha, PhD, and J.P. Cartailler, PhD, of Creative Data Solutions, a shared resource in the Vanderbilt Center for Stem Cell Biology, Vanderbilt postdoctoral fellow Cristiane dos Santos, PhD, and colleagues from the Salk Institute of Biological Studies and University of Alberta.
The research was supported in part by National Institutes of Health grants DK120447, DK097771, and CA014195, the Chapman Foundation, and the Leona M. and Harry B. Helmsley Charitable Trust.
