Decreased mitochondrial DNA content in peripheral blood precedes the development of non-insulin-dependent diabetes mellitus

Lee, H.K; Song, Jihyun; Shin, Chan Soo; Park, D.J; Park, K.S; Lee, K.U; Koh, Chang-Soon

doi:10.1016/s0168-8227(98)00110-7

Cited by 193 publications

(160 citation statements)

References 19 publications

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“…Aging is known to be associated with deletions and mutations of mtDNA resulting from the combined effects of intense oxidative damage (20) and the low efficiency of the mtDNA repair system (21). Age-dependent decline of pb-mtDNA was observed in the present study as well as in our previous study (7).…”

Section: Pb-mtdna Content and Insulin Sensitivitysupporting

confidence: 84%

“…Peripheral blood could provide an alternative sample type to skeletal muscle in the diagnosis of mitochondrial pathology because the data on the mitochondrial state in skeletal muscles and peripheral blood lymphocytes were comparable (8). Decreased pb-mtDNA was found to be related to insulin resistance or the development of type 2 diabetes (7).…”

mentioning

confidence: 99%

“…Decreased mtDNA content was also found in the skeletal muscle of type 1 and type 2 diabetic patients (6). Although the changes resulting from diabetes might influence the mtDNA content, decreases in peripheral blood mtDNA (pb-mtDNA) were observed before the onset of diabetes (7). Peripheral blood could provide an alternative sample type to skeletal muscle in the diagnosis of mitochondrial pathology because the data on the mitochondrial state in skeletal muscles and peripheral blood lymphocytes were comparable (8).…”

mentioning

confidence: 99%

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Peripheral Blood Mitochondrial DNA Content Is Related to Insulin Sensitivity in Offspring of Type 2 Diabetic Patients

Song¹,

Sung

et al. 2001

Diabetes Care

124

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OBJECTIVE -To investigate whether the peripheral blood mtDNA (pb-mtDNA) content is decreased and linked to insulin resistance in the offspring of type 2 diabetic patients.RESEARCH DESIGN AND METHODS -A total of 82 offspring of type 2 diabetic patients and 52 age-, sex-, and BMI-matched normal subjects from the Mokdong, Korea, population were selected for this study by stratified, randomized sampling. Of the offspring of diabetic patients, 52 had normal glucose tolerance (NGT), 21 had impaired glucose tolerance (IGT), and 9 had newly diagnosed type 2 diabetes. The pb-mtDNA content was measured by real-time polymerase chain reaction with a mitochondria-specific fluorescent probe, normalized by a nuclear DNA, 28S rRNA gene. The associations between pb-mtDNA content and several parameters of insulin resistance were studied.RESULTS -The pb-mtDNA contents tended to be lower in the 82 offspring of type 2 diabetic patients (1,084.7 Ϯ 62.6 vs. 1,304.0 Ϯ 99.2 in the offspring and control subjects, respectively, P ϭ 0.051) and was significantly lower in the combined NGT and IGT offspring group (NGTϩIGT, 1,068.0 Ϯ 67.8, P Ͻ 0.05) than in the control subjects. In NGTϩIGT offspring, the pb-mtDNA content was significantly correlated with logarithmically transformed insulin sensitivity (r ϭ 0.253, P Ͻ 0.05) and was the main predictor of insulin sensitivity.CONCLUSIONS -Quantitative mtDNA status might be a hereditary factor associated with type 2 diabetes and could serve as an indicator for insulin sensitivity. Diabetes Care 24:865-869, 2001T he mitochondria are the major site of intracellular respiration and energy metabolism, and their function is intimately related to insulin secretion and possibly insulin action (1,2). Moreover, the mitochondria contain their own genome, with mtDNA coding for some proteins of the respiratory chain. The mutation of mtDNA was believed to cause ϳ0.5-1% of diabetes (3,4). The content of mtDNA is vital for maintaining the mitochondrial function and the energy demands of the body, but little attention has been paid to the quantitative aspects of mtDNA in diabetes. Several animal and human studies have described variations in mtDNA content. Decreased mtDNA content was found in the pancreatic islets of diabetes-prone Goto-Kakizaki rats (5) and in mitochondrial transcriptional factor A (Tfam)-defective mice (4). Decreased mtDNA content was also found in the skeletal muscle of type 1 and type 2 diabetic patients (6). Although the changes resulting from diabetes might influence the mtDNA content, decreases in peripheral blood mtDNA (pb-mtDNA) were observed before the onset of diabetes (7). Peripheral blood could provide an alternative sample type to skeletal muscle in the diagnosis of mitochondrial pathology because the data on the mitochondrial state in skeletal muscles and peripheral blood lymphocytes were comparable (8). Decreased pb-mtDNA was found to be related to insulin resistance or the development of type 2 diabetes (7).Although maximum oxygen consumption (VO 2max ) was positively related to m...

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Section: Pb-mtdna Content and Insulin Sensitivitysupporting

confidence: 84%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Peripheral Blood Mitochondrial DNA Content Is Related to Insulin Sensitivity in Offspring of Type 2 Diabetic Patients

Song¹,

Sung

et al. 2001

Diabetes Care

124

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“…28 Type 2 diabetic patients were found to have significantly decreased content of mtDNA and the lower mtDNA levels preceded the development of diabetes. 29 Depletion of mtDNA in MIN6 cells resulted in loss of ability to release insulin by glucose stimulation which was restored by introduction of mtDNA into the knockout cells. 30 Thus high glucose exposure induced reduction in the expression of mitochondrial aconitase may result in Table 1 were incubated for 60 minutes.…”

Section: Discussionmentioning

confidence: 99%

Mitochondrial proteome analysis reveals altered expression of voltage dependent anion channels in pancreatic β-cells exposed to high glucose

Ahmed¹,

Muhammed²,

Kessler³

et al. 2010

Islets

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“…12 Regarding kidney function, higher mtDNA copy number in peripheral blood has been associated with lower risk of diabetes, a risk factor of CKD, and lower prevalence of albuminuria, a marker of kidney damage. 13,14 Evaluating the association between mtDNA copy number in peripheral blood and kidney function can yield insight into the relationship between mitochondrial dysfunction in blood cells and CKD. We estimated mtDNA copy number using microarray probe intensities of mitochondrial single nucleotide polymorphisms (SNPs).…”

mentioning

confidence: 99%

Association between Mitochondrial DNA Copy Number in Peripheral Blood and Incident CKD in the Atherosclerosis Risk in Communities Study

Tin

Grams²,

Ashar

et al. 2016

JASN

122

115

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Mitochondrial dysfunction in kidney cells has been implicated in the pathogenesis of CKD. Mitochondrial DNA (mtDNA) copy number is a surrogate measure of mitochondrial function, and higher mtDNA copy number in peripheral blood has been associated with lower risk of two important risk factors for CKD progression, diabetes and microalbuminuria. We evaluated whether mtDNA copy number in peripheral blood associates with incident CKD in a population-based cohort of middle-aged adults. We estimated mtDNA copy number using 25 high-quality mitochondrial single nucleotide polymorphisms from the Affymetrix 6.0 array. Among 9058 participants, those with higher mtDNA copy number had a lower rate of prevalent diabetes and lower C-reactive protein levels and white blood cell counts. Baseline eGFR did not differ significantly by mtDNA copy number. Over a median follow-up of 19.6 years, 1490 participants developed CKD. Higher mtDNA copy number associated with lower risk of incident CKD (highest versus lowest quartile: hazard ratio 0.65; 95% confidence interval, 0.56 to 0.75; P,0.001) after adjusting for age, sex, and race. After adjusting for additional risk factors of CKD, including prevalent diabetes, hypertension, C-reactive protein level, and white blood cell count, this association remained significant (highest versus lowest quartile: hazard ratio 0.75; 95% confidence interval, 0.64 to 0.87; P,0.001). In conclusion, higher mtDNA copy number associated with lower incidence of CKD independent of traditional risk factors and inflammation biomarker levels in this cohort. Further research on modifiable factors influencing mtDNA copy number may lead to improvement in the prevention and treatment of CKD.

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Decreased mitochondrial DNA content in peripheral blood precedes the development of non-insulin-dependent diabetes mellitus

Cited by 193 publications

References 19 publications

Peripheral Blood Mitochondrial DNA Content Is Related to Insulin Sensitivity in Offspring of Type 2 Diabetic Patients

Peripheral Blood Mitochondrial DNA Content Is Related to Insulin Sensitivity in Offspring of Type 2 Diabetic Patients

Mitochondrial proteome analysis reveals altered expression of voltage dependent anion channels in pancreatic β-cells exposed to high glucose

Association between Mitochondrial DNA Copy Number in Peripheral Blood and Incident CKD in the Atherosclerosis Risk in Communities Study

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