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Mitochondria-Targeted Small Peptide, SS31 Ameliorates Diabetes Induced Mitochondrial Dynamics in Male TallyHO/JngJ Mice
- Source :
- Mol Neurobiol
- Publication Year :
- 2020
- Publisher :
- Springer Science and Business Media LLC, 2020.
-
Abstract
- The escalating burden of type 2 diabetes (T2D) and its related complications, has become a major public health challenge worldwide. Substantial evidence indicates that T2D is one of the culprits for the high prevalence of Alzheimer’s disease (AD) in diabetic subjects. This study aimed to investigate the possible mitochondrial alterations in the pancreas induced by hyperglycemia in diabetes. We used a diabetic TallyHO/JngJ (TH), and non-diabetic, SWR/J mice strains. The diabetic and non-diabetic status in animals was assessed by performing intraperitoneal glucose tolerance test at four-time points i.e., 4-, 8-, 16- and 24-weeks of age. We divided 24 weeks old TH and SWR/J mice into 3 groups: Controls, diabetic TH mice, and diabetic TH mice treated with SS31 peptide. After the treatment of male TH mice with SS31, intraperitoneally, for 4 weeks, we studied mitochondrial dynamics, biogenesis, and function. The mRNA and protein expression levels of mitochondrial proteins were evaluated using qPCR and immunoblot analysis. The diabetic mice after 24 weeks of age, showed overt pancreatic injury as demonstrated by disintegration, and atrophy of β-cells with vacuolization and reduced islet size. Mitochondrial dysfunction was observed in TH mice, as evidenced by significantly elevated H(2)O(2) production, lipid peroxidation, and reduced ATP production. Furthermore, mRNA expression and immunoblot analysis of mitochondrial dynamics genes were significantly affected in diabetic mice, compared to controls. However, treatment of animals with SS31 reduced mitochondrial dysfunction and restored most of the mitochondrial functions, and mitochondrial dynamics processes to near normal in TH mice. In conclusion, mitochondrial dysfunction is established as one of the molecular events that occur in the pathophysiology of T2D. Further, SS31 treatment may confer protection against the mitochondrial alterations induced by hyperglycemia in diabetic TallyHO/JngJ mice.
- Subjects :
- Blood Glucose
Male
0301 basic medicine
medicine.medical_specialty
Neuroscience (miscellaneous)
Type 2 diabetes
medicine.disease_cause
Mitochondrial Dynamics
Article
Diabetes Mellitus, Experimental
Mice
03 medical and health sciences
Cellular and Molecular Neuroscience
Adenosine Triphosphate
0302 clinical medicine
Atrophy
Diabetes mellitus
Internal medicine
medicine
Animals
RNA, Messenger
Glucose tolerance test
geography
geography.geographical_feature_category
medicine.diagnostic_test
business.industry
Body Weight
Fasting
Glucose Tolerance Test
medicine.disease
Islet
Pathophysiology
Mitochondria
030104 developmental biology
Endocrinology
Neurology
Vacuolization
Hyperglycemia
Female
Lipid Peroxidation
Insulin Resistance
business
Oligopeptides
030217 neurology & neurosurgery
Oxidative stress
Subjects
Details
- ISSN :
- 15591182 and 08937648
- Volume :
- 58
- Database :
- OpenAIRE
- Journal :
- Molecular Neurobiology
- Accession number :
- edsair.doi.dedup.....fd4690cd7f49d5e01c124531436a971e