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High-resolution Respirometry to Measure Mitochondrial Function of Intact Beta Cells in the Presence of Natural Compounds
Published on: January 23, 2018
Trim67 alleviates lipotoxicity-induced β-cell dysfunction by modulating Sirt1-mediated mitochondrial function
Liting Wu1, Qin Xiong2, Fang Zou3
1Department of Endocrinology and Metabolism, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, 330006, China; Department of Endocrinology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, 510080, China.
Molecular and Cellular Endocrinology
|July 24, 2026
Summary
Klf6 activates Trim67, which stabilizes Sirt1 and improves mitochondrial function in beta cells, offering a new therapeutic target for diabetes treatment.
Area of Science:
- Endocrinology
- Molecular Biology
- Mitochondrial Biology
Background:
- Beta-cell dysfunction is central to diabetes progression.
- Lipotoxicity impairs beta-cell mitochondrial function through unclear mechanisms.
Purpose of the Study:
- To elucidate the molecular mechanisms underlying lipotoxicity-induced beta-cell mitochondrial dysfunction.
- To investigate the role of Trim67 in regulating beta-cell function and mitochondrial health.
Main Methods:
- Utilized diabetic db/db mice and palmitic acid-treated MIN6 cells to model lipotoxicity.
- Employed Co-IP, ChIP, and dual-luciferase assays to study protein interactions and transcriptional regulation.
- Assessed beta-cell mitochondrial function using JC-1, Seahorse XF-96, and ATP detection kits.
Main Results:
- Trim67 expression was reduced in diabetic islets and lipotoxic beta-cells.
- Overexpression of Trim67 improved glucose tolerance and insulin secretion in diabetic mice.
- Trim67 enhanced beta-cell mitochondrial function by stabilizing Sirt1 via ubiquitination, activating the Sirt1/Pgc-1α pathway.
Conclusions:
- Klf6 transcriptionally activates Trim67, which regulates the Sirt1/Pgc-1α pathway to mitigate lipotoxicity-induced mitochondrial dysfunction in beta cells.
- This pathway presents a novel therapeutic strategy for diabetes.