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- Title
Advanced Glycation End Products (AGEs) Cause β-Cell Dysfunction in Mice by Impairing Mitochondrial Function.
- Authors
Zhengshan Zhao; Xu Zhang; Chunying Zhao; Feng Zheng; Weijing Cai; Vlassara, Helen; Ma, Zhongmin A.
- Abstract
Advanced glycation end products (AGEs) have been implicated in diabetic complications. Recent studies showed that dietary AGEs promote T1D, T2D and insulin resistance in mice, suggesting a role for AGEs in the pathogenesis of diabetes. In this study, we investigated whether AGEs have a toxic effect on β-cells in vivo. AGE-BSA or BSA were administered daily for two weeks to normal C57/BL6 mice (100 µg/g body weight, i.p.) (n = 8/group) and metabolic and islet functions were assessed. We found that levels of fasting plasma glucose in the AGE-BSA treated group (131±12 mg/dl) was significantly increased compared to that in the BSA treated group (95±10 mg/dl) (P < 0.05). Whereas high glucose-stimulated (16.7 mM glucose, ip) insulin secretion by islets isolated from BSA-treated mice was 3 times higher (24.5 ± 11.68 ng/mg/h) compared to low (1.7 mM) glucose (7.32 ± 2.97 ng/mg/h), levels of high-glucose insulin secreted by islets from the AGE-BSA treated mice did not differ (13.57 ± 6.76 ng/mg/h) from those in response to low-glucose (1.7 mM) stimulation (13.74 ± 7.68 ng/mg/h). Moreover, the total islet insulin content was decreased in the AGE-BSA treated mice (0.437 ± 0.063 ng/10 islets) compared to BSA-treated controls (1.014 ± 0.138 ng/10 islets), suggesting βcell dysfunction in AGE-treated mice. To investigate the cellular mechanism of β-cell dysfunction, INS-1 cells were cultured in the presence of AGE-BSA (200 µg/ml) or BSA for 24 hours and mitochondrial function was analyzed by JC-1 staining and FACS. We found that AGE decreased mitochondrial membrane potential in INS-1 cells. Thus, exposure to exogenous AGE, especially from diet may impair β-cell mitochondrial function, leading to β-cell insulin secretion impairment and diabetes. ADA-Funded Research
- Subjects
DIABETES complications; PANCREATIC beta cells; LABORATORY mice; MITOCHONDRIA; INSULIN resistance
- Publication
Diabetes, 2007, Vol 56, pA687
- ISSN
0012-1797
- Publication type
Academic Journal