Obesity increases the risk of developing type 2 diabetes mellitus (T2DM). However, it is incompletely understood why some individuals with obesity develop the disease and others do not.
To answer this question, Mototsugu Nagao, Lena Eliasson and colleagues studied pancreatic islets from people with obesity who had developed T2DM and compared them with islets from people with obesity who had not developed T2DM.
“When Mototsugu Nagao came to my laboratory, he had published a paper describing that pancreatic islets from mice prone to diet-induced diabetes mellitus had high expression of the fatty acid transporter CD36 (Cd36) and, at the same time, lower expression of some exocytotic genes,” says Eliasson, co-corresponding author of the study. “We decided to investigate together if this was also the case in human islets, and if it might have a pathogenic role in T2DM in relation to obesity.”
The researchers observed that islets from donors with obesity-associated T2DM had reduced insulin secretion and β-cell exocytosis compared with islets from donors with obesity but not T2DM. Furthermore, dysfunctional insulin secretion and impaired exocytosis were associated with increased expression of CD36.
Using a rat-derived β-cell line the team investigated the mechanisms underlying the human findings. Their findings suggest that increased levels of CD36 modulate β-cell insulin signalling and suppress insulin granule exocytosis.
To test the therapeutic potential of their work, the researchers treated a human β-cell line with CD36-neutralizing antibodies. They observed that the treatment increased the expression of exocytosis-associated proteins and enhanced insulin secretion. “Taken together, our findings further highlight the pathogenic role of β-cell CD36 in the development of T2DM, especially in relation to obesity,” explains Eliasson.
“We believe that the blockage of CD36 function could be an attractive approach to improve insulin secretion, especially in obesity-related T2DM,” summarizes Eliasson. “A further study to test the CD36-neutralizing antibody on human islets of donors with obesity and T2DM is warranted as the next step.”
Nagao, M. et al. Potential protection against type 2 diabetes in obesity through lower CD36 expression and improved exocytosis in β-cells. Diabetes https://doi.org/10.2337/db19-0944 (2020)
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Kriebs, A. β-cell CD36 linked to insulin secretion. Nat Rev Endocrinol 16, 300 (2020). https://doi.org/10.1038/s41574-020-0360-x