September 8, 2022

Immune cells drive beta cell loss in Type 2 diabetes

Vanderbilt researchers have discovered details of pancreatic beta cell loss — and potential therapeutic targets — during conditions of overnutrition, as occurs in obesity.

Obesity and overnutrition increase the risk of Type 2 diabetes through several mechanisms. One of these is through loss of the insulin-producing beta cells of the pancreatic islet. 

Wenbiao Chen, PhD, and colleagues previously have shown that overnutrition stressed the endoplasmic reticulum, the part of the beta cell essential for producing insulin. This caused the secretion of inflammatory signals that attract macrophages, a type of immune cell. 

Using live imaging in a zebrafish model in a new study, they demonstrated that the macrophages induced beta cells to express CXCL8, a potent signaling protein. CXCL8, in turn, recruited neutrophils, another type of immune cell, which attacked and killed macrophage-associated beta cells. 

Investigation of two mouse models confirmed that macrophages and neutrophils are increased in Type 2 diabetes and play a role in pathogenesis. 

These findings, published in Cell Reports, suggest that overnutrition-induced beta-cell death involves intricate communication between beta cells and immune cells. Targeting these signaling pathways may prevent beta cell loss. 

VUMC co-authors include Bingyuan Yang, PhD, Liu Yang, PhD, Zihan Tang, Sander Haigh, Yulong Gong, Yue Zhang, PhD, Brittney Covington, Karin Bosma, PhD, Xin Tong, PhD, Patrick Page-McCaw, PhD, and Maureen Gannon, PhD. 

This study was supported by National Institutes of Health grants DK117147, DK020593, GM119787, and DK007563, and the China Scholarship Council.