Cited by 41Mitochondrial Function and PathologyPancreatic function and diabetesAutophagy in Disease and Therapy

Mitochondria-Targeted Small Peptide, SS31 Ameliorates Diabetes Induced Mitochondrial Dynamics in Male TallyHO/JngJ Mice

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Bhatti, Jasvinder Singh, Thamarai, Kavya, Kandimalla, Ramesh, Manczak, Maria, Yin, Xiangling, Kumar, Subodh, Vijayan, Murali, Reddy, P. Hemachandra·2021·Molecular Neurobiology

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-week-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 with 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.

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  • In type 2 diabetes, animal models and human islet and leukocyte samples provide evidence that elamipretide improves mitochondrial function.

    “studies using animal models and human islet and leukocyte samples support the beneficial effects of elamipretide in improving mitochondrial function288,289”

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  1. [34]Mathews CE, Leiter EH (2005) Rodent models for the study of diabetes In: Kahn CR, Weir GC, King GL, Jacobson AM, Moses AC, Smith RJ (eds) Joslin’s Diabetes Mellitus. 14 edn. Lippincott Williams, Willkins, Philadelphia, pp 292– 328
  2. [57]Bhatti JS, Bhatti GK, Reddy PH (2017) Mitochondrial dysfunction and oxidative stress in metabolic disorders - A step towards mitochondria based therapeutic strategies. Biochim Biophys Acta Mol Basis Dis 1863 (5): 1066– 1077. doi: 10.1016/j.bbadis.2016.11.010 27836629 PMC5423868 · DOI · Paper page

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Authors
Bhatti, J. S., Thamarai, K., Kandimalla, R., Manczak, M., Yin, X., Kumar, S., Vijayan, M., & Reddy, P. H.
Affiliations
  • Central University of Punjab (IN)
  • Texas Tech University Health Sciences Center (US)
  • Kakatiya Medical College (IN)
  • Texas Tech University (US)
Corresponding author
Reddy, P. Hemachandra
Venue
Molecular Neurobiology
Published
2020-10-07
Volume
58
Issue
2
Pages
795-808
ISSN
  • 0893-7648 (ISSN-L)
  • 1559-1182
OpenAlex
W3092219155
Cited by
41
References
96
Citations by year
2026: 2 · 2025: 8 · 2024: 6 · 2023: 6 · 2022: 11 · 2021: 6
FWCI
1.87
Type
journal article
Language
en
Open access
Locations
  • Molecular Neurobiology (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
National Institutes of Health (AG042178, AG047812, NS105473, AG060767 and AG069333)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
  • Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
  • Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
Keywords
SS-31, mitochondria-targeted peptide, type 2 diabetes, mitochondrial dynamics, mitochondrial dysfunction, pancreatic beta cells, hyperglycemia, mitochondrial biogenesis, oxidative stress, lipid peroxidation, ATP production, Alzheimer's disease
MeSH terms
Adenosine Triphosphate, Animals, Blood Glucose, Body Weight, Diabetes Mellitus, Experimental, Fasting, Female, Glucose Tolerance Test, Hyperglycemia, Insulin Resistance, Male, Mitochondria, Oligopeptides, RNA, Messenger, Lipid Peroxidation, Mice, Mitochondrial Dynamics

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