Mitochondrial dysfunction and complications associated with diabetes

Biochim Biophys Acta. 2014 Apr;1840(4):1404-12. doi: 10.1016/j.bbagen.2013.11.007. Epub 2013 Nov 15.


Background: Diabetes is a metabolic syndrome that results in chronically increased blood glucose (hyperglycaemia) due to defects either in insulin secretion consequent to the loss of beta cells in the pancreas (type 1) or to loss of insulin sensitivity in target organs in the presence of normal insulin secretion (type 2). Long term hyperglycaemia can lead to a number of serious health-threatening pathologies, or complications, especially in the kidney, heart, retina and peripheral nervous system.

Scope of review: Here we summarise the current literature on the role of the mitochondria in complications associated with diabetes, and the limitations and potential of rodent models to explore new modalities to limit complication severity.

Major conclusions: Prolonged hyperglycaemia results in perturbation of catabolic pathways and in an over-production of ROS by the mitochondria, which in turn may play a role in the development of diabetic complications. Furthermore, current models don't offer a comprehensive recapitulation of these complications.

General significance: The onset of complications associated with type 1 diabetes can be varied, even with tightly controlled blood glucose levels. The potential role of inherited, mild mitochondrial dysfunction in accelerating diabetic complications, both in type 1 and 2 diabetes, remains unexplored. This article is part of a Special Issue entitled Frontiers of Mitochondrial Research.

Keywords: Complication; Diabetes; Mitochondria; Mouse model; Oxidative phosphorylation; Reactive oxygen species.

Publication types

  • Review

MeSH terms

  • Diabetes Mellitus, Type 1 / complications*
  • Diabetes Mellitus, Type 1 / drug therapy
  • Diabetes Mellitus, Type 1 / physiopathology
  • Diabetes Mellitus, Type 2 / complications*
  • Diabetes Mellitus, Type 2 / drug therapy
  • Diabetes Mellitus, Type 2 / physiopathology
  • Humans
  • Hyperglycemia / complications
  • Hyperglycemia / drug therapy
  • Hyperglycemia / physiopathology
  • Insulin / pharmacology
  • Insulin / therapeutic use
  • Metformin / pharmacology
  • Metformin / therapeutic use
  • Mitochondria / drug effects
  • Mitochondria / physiology*
  • Mitochondrial Diseases / etiology*
  • Mitochondrial Diseases / physiopathology


  • Insulin
  • Metformin