Mitochondrial factors in the pathogenesis of diabetes: a hypothesis for treatment.
A growing body of evidence has demonstrated a link between various disturbances in mitochondrial functioning and type 2 diabetes. This review focuses on a range of mitochondrial factors important in the pathogenesis of this disease. The mitochondrion is an integral part of the insulin system found in the islet cells of the pancreas. Because of the systemic complexity of mitochondrial functioning in terms of tissue and energetic thresholds, details of structure and function are reviewed. The expression of type 2 diabetes can be ascribed to a number of qualitative or quantitative changes in the mitochondria. Qualitative changes refer to genetic disturbances in mitochondrial DNA (mtDNA). Heteroplasmic as well as homoplasmic mutations of mtDNA can lead to the development of a number of genetic disorders that express the phenotype of type 2 diabetes. Quantitative decreases in mtDNA copy number have also been linked to the pathogenesis of diabetes. The study of the relationship of mtDNA to type 2 diabetes has revealed the influence of the mitochondria on nuclear-encoded glucose transporters and the influence of nuclear encoded uncoupling proteins on the mitochondria. This basic research into the pathogenesis of diabetes has led to the awareness of natural therapeutics (such as coenzyme Q10) that increase mitochondrial functioning and avoidance of trans-fatty acids that decrease mitochondrial functioning.
Lamson
Davis W
DW
Bastyr University, Kenmore, WA, USA. davisl@seanet.com
Plaza
Steven M
SM
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002352:Carrier Proteins / Q000502:physiology; D003067:Coenzymes; D004272:DNA, Mitochondrial / Q000235:genetics*; D003924:Diabetes Mellitus, Type 2 / Q000209:etiology* / Q000628:therapy*; D004041:Dietary Fats / Q000009:adverse effects; D005947:Glucose / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000378:metabolism; D007473:Ion Channels; D008565:Membrane Proteins / Q000502:physiology; D008928:Mitochondria / Q000502:physiology*; D024101:Mitochondrial Proteins; D009154:Mutation; D051381:Rats; D014451:Ubiquinone / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D000071256:Uncoupling Protein 1
D002352:Carrier Proteins; D003067:Coenzymes; D004272:DNA, Mitochondrial; D004041:Dietary Fats; D007328:Insulin; D007473:Ion Channels; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D000071256:Uncoupling Protein 1; D014451:Ubiquinone; D000255:Adenosine Triphosphate; C024989:coenzyme Q10; D005947:Glucose