May 20, 2021

Beta cell regeneration

Vanderbilt researchers dissected the complex microenvironment of the pancreatic islet to discover the signals that drive beta cell regeneration — as a possible treatment for diabetes.

Promoting the regeneration of insulin-producing beta cells could be an effective treatment for diabetes, but the stimuli that boost beta cell proliferation are not completely understood. 

Marcela Brissova, PhD, Diane Saunders, PhD, and colleagues previously characterized an animal model in which signals from the local islet microenvironment — and interactions with endothelial cells (ECs) and macrophages — stimulated self-renewal of both human and mouse beta cells. 

The investigators have now developed experimental tools to dissect the complex islet microenvironment in this model. They demonstrated that ECs modulate macrophage recruitment and phenotype and that macrophages are essential for beta cell recovery. Transcriptome analysis of beta cells, ECs and macrophages revealed elevated expression of extracellular matrix remodeling molecules and growth factors that likely drive proliferative signaling pathways in beta cells. 

The findings, reported in npj Regenerative Medicine, suggest that macrophages, ECs and extracellular matrix cooperatively promote beta cell regeneration.

This research was supported by grants from the Department of Veterans Affairs, JDRF, National Institutes of Health (DK106755, DK089572, DK066636, DK069603, DK063439, DK062641, DK072473, DK094199, DK068764, DK097829, DK011232, DK117147, DK104211), and the Vanderbilt Diabetes Research and Training Center (supported by NIH grant DK020593).