Researchers have found a novel way to reverse established diabetes in mice, and in the process, unraveled an approach that could potentially be exploited to treat pre-existing diabetes in humans.
Men1 excision dramatically increases a marker of pancreatic beta cell proliferation (orange dots). Click to view full-size image with comparison. Credit: Yuqing Yang, MD, PhD, University of Pennsylvania School of Medicine
Xianxin Hua, MD, PhD, associate professor of Cancer Biology at the Abramson Family Cancer Research Institute at the University of Pennsylvania School of Medicine, and colleagues report in the Proceedings of the National Academy of Sciences, that deletion of the Men1 gene, which encodes the protein menin, reversed pre-existing high blood sugar in mice with diabetes. What’s more, the Men1 deletion also ameliorated the pre-existing high blood sugar and glucose intolerance (a condition of pre-diabetes) in mice with inherited diabetes, as well as reversed pre-existing glucose intolerance in high-fat-diet-fed mice, a model mimicking human type 2 diabetes.
These findings in three different models of diabetes point to the fact that improved glucose metabolism happens at least partly by increasing the number of functional beta cells and increasing the size of islet cells. Hua says that the study shows, above all, that established hyperglycemia can be reversed through repression of a single gene, versus classic approaches on prevention of development of diabetes after a gene is deleted. These novel findings strongly suggest that menin is a vital regulator in pathogenesis of diabetes, and importantly a potential new target to treating diabetes.
Other Penn researchers who have contributed to these studies are Yuqing Yang, Buddha Gurung, Haoren Wang, Wing Wu, and Doris Stoffers.
