Skeletal muscle mitochondrial functions, mitochondrial DNA copy numbers, and gene transcript profiles in type 2 diabetic and nondiabetic subjects at equal levels of low or high insulin and euglycemia.

We investigated whether previously reported muscle mitochondrial dysfunction and altered gene transcript levels in type 2 diabetes might be secondary to abnormal blood glucose and insulin levels rather than an intrinsic defect of type 2 diabetes. A total of 13 type 2 diabetic and 17 nondiabetic subj...

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Publicado en:Diabetes Vol. 55; no. 12; pp. 3309 - 3320
Autores principales: Asmann YW, Stump CS, Short KR, Coenen-Schimke JM, Guo Z, Bigelow ML, Nair KS
Formato: research tables/charts Journal Article
Publicado: American Diabetes Association Dec2006
Acceso en línea:Ver este registro en EBSCOhost
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      dt: Dec2006
      vid: 55
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      pub: American Diabetes Association
      place: Arlington, Virginia
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        2009376985
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        atl: Skeletal muscle mitochondrial functions, mitochondrial DNA copy numbers, and gene transcript profiles in type 2 diabetic and nondiabetic subjects at equal levels of low or high insulin and euglycemia.
      aug:
        au:
          Asmann YW
          Stump CS
          Short KR
          Coenen-Schimke JM
          Guo Z
          Bigelow ML
          Nair KS
        affil: Endocrinology Research Unit, Mayo Clinic, 200 First St. SW, Joseph 5-194, Rochester, MN 55905, USA.
      sug:
        subj:
          Diabetes Mellitus, Type 2
          Insulin Metabolism
          Mitochondria Analysis
          Muscle, Skeletal
          Biopsy
          Blood Glucose Analysis
          Blotting, Western
          Descriptive Statistics
          Female
          Funding Source
          Male
          Middle Age
          P-Value
          Unpaired T-Tests
          Human
          Middle Aged: 45-64 years
          Female
          Male
      ab: We investigated whether previously reported muscle mitochondrial dysfunction and altered gene transcript levels in type 2 diabetes might be secondary to abnormal blood glucose and insulin levels rather than an intrinsic defect of type 2 diabetes. A total of 13 type 2 diabetic and 17 nondiabetic subjects were studied on two separate occasions while maintaining similar insulin and glucose levels in both groups by 7-h infusions of somatostatin, low- or high-dose insulin (0.25 and 1.5 mU/kg of fat-free mass per min, respectively), and glucose. Muscle mitochondrial DNA abundance was not different between type 2 diabetic and nondiabetic subjects at both insulin levels, but the majority of transcripts in muscle that are involved mitochondrial functions were expressed at lower levels in type 2 diabetes at low levels of insulin. However, several gene transcripts that are specifically involved in the electron transport chain were expressed at higher levels in type 2 diabetic patients. After the low-dose insulin infusion, which achieved postabsorptive insulin levels, the muscle mitochondrial ATP production rate (MAPR) was not different between type 2 diabetic and nondiabetic subjects. However, increasing insulin to postprandial levels increased the MAPR in nondiabetic subjects but not in type 2 diabetic patients. The lack of MAPR increment in response to high-dose insulin in type 2 diabetic patients occurred in association with reduced glucose disposal and expression of peroxisome proliferator-activated receptor-gamma coactivator 1alpha, citrate synthase, and cytochrome c oxidase I. In conclusion, the current data supports that muscle mitochondrial dysfunction in type 2 diabetes is not an intrinsic defect, but instead a functional defect related to impaired response to insulin.
      pubtype: Academic Journal
      doctype:
        research
        tables/charts
        Journal Article
      ougenre: Article
    language: English
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