Role of mitochondrial DNA variation in the pathogenesis of diabetes mellitus

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Mitochondria are crucial intracellular organelles where ATP and reactive oxygen species are generated via the electron transport chain. They are also where cellular fate is determined. There is a growing body of evidence that mitochondrial dysfunction plays an important role in the pathogenesis of type 2 diabetes. Mitochondrial dysfunction in pancreatic beta-cells results in impaired glucose-stimulated insulin secretion. It is also associated with decreased oxidative phosphorylation and fatty acid oxidation in insulin sensitive tissues. Variation in mitochondrial DNA (mtDNA) quantity and quality are reported to be associated with the risk of developing diabetes. A rare variant, mtDNA 3243 A>G, is well known to cause maternally inherited diabetes. Common mtDNA variants, such as mtDNA 16189 T>C and several mtDNA haplogroups, are also associated with an increased risk of diabetes, especially in Asians. The variant load, known as heteroplasmy, in a specific tissue is thought to modulate the phenotypic expression of these mtDNA variants. In this article, we review the role of mitochondrial dysfunction in the pathogenesis of diabetes and the association between mtDNA variations and risk of diabetes.

Original languageEnglish
Pages (from-to)1151-1167
Number of pages17
JournalFrontiers in Bioscience - Landmark
Volume21
Issue number6
StatePublished - 1 Jun 2016

Fingerprint

Medical problems
Mitochondrial DNA
Diabetes Mellitus
Insulin
Tissue
Mitochondria
Oxidative Phosphorylation
Insulin-Secreting Cells
Electron Transport
Organelles
Type 2 Diabetes Mellitus
Reactive Oxygen Species
Fatty Acids
Adenosine Triphosphate
Association reactions
Glucose
Oxidation

Keywords

  • ATP
  • Beta-cell dysfunction
  • Diabetes
  • Heteroplasmy
  • Mitochondrial DNA
  • Reactive oxygen species
  • Review
  • Variation

Cite this

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Role of mitochondrial DNA variation in the pathogenesis of diabetes mellitus. / Kwak, Soo Heon; Park, Kyong Soo.

In: Frontiers in Bioscience - Landmark, Vol. 21, No. 6, 01.06.2016, p. 1151-1167.

Research output: Contribution to journalArticle

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AB - Mitochondria are crucial intracellular organelles where ATP and reactive oxygen species are generated via the electron transport chain. They are also where cellular fate is determined. There is a growing body of evidence that mitochondrial dysfunction plays an important role in the pathogenesis of type 2 diabetes. Mitochondrial dysfunction in pancreatic beta-cells results in impaired glucose-stimulated insulin secretion. It is also associated with decreased oxidative phosphorylation and fatty acid oxidation in insulin sensitive tissues. Variation in mitochondrial DNA (mtDNA) quantity and quality are reported to be associated with the risk of developing diabetes. A rare variant, mtDNA 3243 A>G, is well known to cause maternally inherited diabetes. Common mtDNA variants, such as mtDNA 16189 T>C and several mtDNA haplogroups, are also associated with an increased risk of diabetes, especially in Asians. The variant load, known as heteroplasmy, in a specific tissue is thought to modulate the phenotypic expression of these mtDNA variants. In this article, we review the role of mitochondrial dysfunction in the pathogenesis of diabetes and the association between mtDNA variations and risk of diabetes.

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