Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.6.5.3 (complex I)
 8,901 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Mitochondrial dysfunctions of the muscle in diabetic amyotrophy and of the liver in diabetic fatty liver have been reported. We investigated mitochondrial gene mutations in three cases: (1) a patient with diabetic amyotrophy in the muscles of the lower extremities, and neuropathy; (2) 5 diabetics with myoatrophy, diabetic nephropathy, and chronic renal failure; and (3) an IDDM patient with a diabetic fatty liver. We identified a 5778-bp deletion (8214-13991) in mitochondrial DNA from the muscle and liver biopsy specimens by the primer shift PCR and PCR-direct sequence methods. It is speculated that 5778-bp deletion is due to homogeneous recombination in the 7-bp repeat sequence of TCCTAGA flanking the region deleted in the mitochondrial DNA. Determination of respiratory chain enzyme activities in fresh muscle mitochondria demonstrated the defect in complex I activity. The deletion covers areas coding ND3, ND4, ND4L, and ND5 in complex I. The 5778-bp deletion might cause a defect in mitochondrial oxidative phosphorylation and contribute to the pathogenesis of diabetic amyotrophy, myoatrophy with diabetic nephropathy, and chronic renal failure, as well as diabetic fatty liver in IDDM.
 ...
PMID:A new mitochondrial DNA deletion associated with diabetic amyotrophy, diabetic myoatrophy and diabetic fatty liver. 760 16

Human intoxication with the rodenticide Vacor [N-3-pyridylmethyl-N'-p-nitrophenyl urea or 1-(4-nitrophenyl)-3-(3-pyridylmethyl) urea] induces acute IDDM. We report here that Vacor specifically inhibits the NADH:ubiquinone reductase activity of complex I in mammalian mitochondria. The activity of other respiratory enzymes of mitochondria is unaffected by Vacor at concentrations that completely inhibit the redox and energetic function of complex I. Vacor inhibition of complex I activity quantitatively correlates with the inhibition of insulin release in insulinoma cells and pancreatic islets and is also consistent with the doses reported in cases of human poisoning. These results indicate that the toxic and diabetogenic action of Vacor primarily derives from the inhibition of mitochondrial respiration of NAD-linked substrates in the high-energy demanding cells of the pancreatic islets. This newly identified mechanism of the pathological effects resulting from Vacor intoxication could constitute a paradigm in which to understand environmental or metabolic causes of IDDM.
 ...
PMID:Inhibition of mitochondrial complex I may account for IDDM induced by intoxication with the rodenticide Vacor. 886 57

To investigate the prevalence of mitochondrial DNA mutations among Japanese children with IDDM as well as in those with NIDDM, a total of 155 patients with IDDM and 30 patients with NIDDM who were younger than 15 years of age at onset were studied for the following mtDNA mutations: 1) the A-->G mutation at position 3243 of mitochondrial leucine transfer RNA (3243 mutation); 2) the G-->A mutation at position 3316 of mitochondrial leucine transfer RNA (3316 mutation), and 3) The T-->C mutation at position 3394 of the mitochondrial NADH dehydrogenase subunit (3394 mutation). None of the 155 IDDM patients had the 3243 mutation. Although two of the 155 IDDM patients had homoplasmy of 3316 and five had 3394 mutations, these frequencies were not significant compared with healthy controls. None of the 30 NIDDM patients had the 3243, 3316 or 3394 mutation. The presence of these mutations even in control subjects suggests that the effect of the 3316 or 3394 mutation on mitochondrial function is relatively mild. It seems that 3316 and 3394 mutations contribute to the manifestation of diabetes together with other genetic and/or environmental factors.
 ...
PMID:The prevalence of mitochondrial gene mutations in childhood diabetes in Japan. 1039 45