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Humanin promotes mitochondrial biogenesis in pancreatic MIN6 β-cells

Journal Article · · Biochemical and Biophysical Research Communications
 [1];  [2];  [1];  [3]; ;  [1];  [3]
  1. Medical Faculty, Kunming University of Science and Technology, Kunming 650500 (China)
  2. State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223 (China)
  3. Institute of Basic and Clinical Medicine, Key Laboratory for Clinical Virology, Key Laboratory for Birth Defects and Genetic Diseases, The First People's Hospital of Yunnan Province, Kunming 650032 (China)

Highlights: • Humanin stimulated the expressions of PGC-1α, NRF1 and TFAM. • Humanin increased Mitochondrial mass, mtDNA/nDNA, and cytochrome B expression. • The effects of Humanin on mitochondrial biogenesis were mediated by AMPK. • Humanin led to a functional gain of the mitochondria. Mitochondrial dysfunction is associated with β-cell failure and insulin resistance in diabetes. Humanin is an endogenous cytoprotective peptide. In the current study, we aimed to define the effects of Humanin on mitochondrial biogenesis in pancreatic β-cells. Our findings demonstrated that Humanin treatment significantly increased the expression of PGC-1α and its downstream target genes NRF1 and TFAM in MIN6 β-cells. Notably, Humanin treatment significantly promoted mitochondrial biogenesis by increasing mitochondrial mass, elevating mtDNA/nDNA ratio, and stimulating the expression of cytochrome B, which were suppressed by the specific AMPK inhibitor compound C. Indeed, Humanin treatment caused the phosphorylation of AMPK, which was involved in the induction of PGC-1α, NRF1, and TFAM by Humanin. Importantly, our findings indicate that Humanin treatment led to a possible functional gain of the mitochondria by increasing ATP levels and respiratory rate. Our findings provided a new insight into the molecular mechanisms of action by which Humanin improves pancreatic β-cell function via enhanced mitochondrial mass and performance.

OSTI ID:
23137331
Journal Information:
Biochemical and Biophysical Research Communications, Journal Name: Biochemical and Biophysical Research Communications Journal Issue: 1 Vol. 497; ISSN 0006-291X; ISSN BBRCA9
Country of Publication:
United States
Language:
English

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