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Diluted serum from calorie-restricted animals promotes mitochondrial β-cell adaptations and protect against glucolipotoxicity
- Source :
- Repositório Institucional da USP (Biblioteca Digital da Produção Intelectual), Universidade de São Paulo (USP), instacron:USP
- Publication Year :
- 2015
-
Abstract
- β-cells quickly adjust insulin secretion to oscillations in nutrients carried by the blood, acting as fuel sensors. However, most studies of β-cell responses to nutrients do not discriminate between fuel levels and signaling components present in the circulation. Here we studied the effect of serum from calorie-restricted rats versus serum from rats fed ad libitum, diluted tenfold in the medium, which did not contribute significantly to the pool of nutrients, on β-cell mitochondrial function and dynamics under regular and high-nutrient culture conditions. Insulin secreting beta-cell derived line (INS1) cells incubated with serum from calorie-restricted rats (CR serum) showed higher levels of peroxisome proliferator-activated receptor gamma coactivator 1-α (PGC-1α) and active nitric oxide synthase. The expression of mitofusin-2 (Mfn-2) and optic atrophy 1 (OPA-1), proteins involved in mitochondrial fusion, was increased, while the levels of the mitochondrial fission mediator dynamin related protein 1 (DRP-1) were reduced. Consistent with changes in mitochondrial dynamics protein levels, CR serum treatment increased mitochondrial fusion rates, as well as their length and connectivity. These changes in mitochondrial morphology were associated with prolonged glucose-stimulated insulin secretion and mitochondrial respiration. When combining CR serum and high levels of glucose and palmitate (20 and 0.4 mm, respectively), an in vitro model of type II diabetes, we observed that signaling promoted by CR serum was enough to overcome glucolipotoxicity, as indicated by CR-mediated prevention of mitochondrial fusion arrest and reduced respiratory function in INS1 cells under glucolipotoxicity. Overall, our results provide evidence that non-nutrient factors in serum have a major impact on β-cell mitochondrial adaptations to changes in metabolism.
- Subjects :
- 0301 basic medicine
Dynamins
Male
medicine.medical_specialty
Nitric Oxide Synthase Type III
Cellular respiration
medicine.medical_treatment
Cell Respiration
Cell Separation
Biology
Mitochondrion
Biochemistry
Mitochondrial Dynamics
Cell Line
GTP Phosphohydrolases
Rats, Sprague-Dawley
03 medical and health sciences
DNM1L
Oxygen Consumption
Internal medicine
Insulin-Secreting Cells
medicine
Animals
Insulin
Respiratory function
Molecular Biology
Caloric Restriction
Cell Biology
medicine.disease
Flow Cytometry
Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
Mitochondria
Rats
030104 developmental biology
Endocrinology
Glucose
mitochondrial fusion
MITOCÔNDRIAS
Optic Atrophy 1
Mitochondrial fission
Transcription Factors
Subjects
Details
- ISSN :
- 17424658
- Volume :
- 283
- Issue :
- 5
- Database :
- OpenAIRE
- Journal :
- The FEBS journal
- Accession number :
- edsair.doi.dedup.....9fdd7efa7cac08ff110299f330efdf75