Pancreatic beta cell senescence contributes to the pathogenesis of type 2 diabetes in high-fat diet-induced diabetic mice
- H. SoneAffiliated withHigh Technology Research Centre, Kagawa Nutrition University
- , Y. KagawaAffiliated withHigh Technology Research Centre, Kagawa Nutrition UniversityDepartment of Biochemistry, Jichi Medical School Email author
During the pathogenesis of type 2 diabetes insulin resistance causes compensatory proliferation of beta cells. As beta cells have a limited replication potential, this compensatory proliferation might accelerate cellular senescence and lead to diabetes. We examined the cellular senescence of beta cells after proliferation during lipoglucotoxicity.
Senescence-associated markers in beta cells were examined in nutrient-induced diabetic C57BL/6J mice that were fed a high-fat diet. After 4 and 12 months of the high-fat diet, intraperitoneal glucose tolerance tests (IPGTTs) and histochemical analyses of Ki-67, p38, senescence-associated beta-galactosidase, and beta cell mass were performed.
At 4 months, the AUC for plasma insulin levels during the IPGTT (AUCinsulin) was higher, beta cell mass was 3.1-fold greater, and the proliferation of beta cells was 2.2-fold higher than in the control group. However, at 12 months, AUCinsulin declined, the frequency of Ki-67-positive beta cells decreased to one-third that of the control group, and the senescence-associated, beta-galactosidase-positive area increased to 4.7-fold that of the control group. Moreover, small amounts of p38, which is induced by oxidative stress and mediates cellular senescence, were found in beta cells from the high-fat diet group, but not in beta cells from the control group. Furthermore, the senescence-associated, beta-galactosidase-positive area in the high-fat diet group had a highly significant negative correlation with AUCinsulin (r=−0.852, p<0.01).
Beta cell senescence occurred in diet-induced type 2 diabetes and led to insufficient insulin release. These findings suggest that cellular senescence contributes to the pathogenesis of diet-induced diabetes.
KeywordsCellular proliferation Cellular senescence High-fat diet Pancreatic beta cell Type 2 diabetes
- Pancreatic beta cell senescence contributes to the pathogenesis of type 2 diabetes in high-fat diet-induced diabetic mice
Volume 48, Issue 1 , pp 58-67
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- Cellular proliferation
- Cellular senescence
- High-fat diet
- Pancreatic beta cell
- Type 2 diabetes
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