Variants in Genes Controlling Oxidative Metabolism Contribute to Lower Hepatic ATP Independent of Liver Fat Content in Type 1 Diabetes.
| Autor: | Gancheva, Sofiya, Bierwagen, Alessandra, Kaul, Kirti, Herder, Christian, Nowotny, Peter, Kahl, Sabine, Giani, Guido, Klueppelholz, Birgit, Knebel, Birgit, Begovatz, Paul, Strassburger, Klaus, Al-Hasani, Hadi, Lundbom, Jesper, Szendroedi, Julia, Roden, Michael, German Diabetes Study (GDS) Group |
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| Předmět: |
TYPE 1 diabetes
FATTY liver METABOLIC disorders ALLELES MITOCHONDRIAL pathology DIAGNOSIS ADENOSINE triphosphate metabolism PHOSPHATE metabolism ADIPOSE tissues ENERGY metabolism GENETIC disorders INSULIN resistance LIPID metabolism disorders LIVER PROTEINS TRIGLYCERIDES OXIDATIVE stress BODY mass index GLUCOSE clamp technique |
| Zdroj: | Diabetes; Jul2016, Vol. 65 Issue 7, p1849-1857, 9p, 3 Charts, 3 Graphs |
| Abstrakt: | Type 1 diabetes has been recently linked to nonalcoholic fatty liver disease (NAFLD), which is known to associate with insulin resistance, obesity, and type 2 diabetes. However, the role of insulin resistance and hyperglycemia for hepatic energy metabolism is yet unclear. To analyze early abnormalities in hepatic energy metabolism, we examined 55 patients with recently diagnosed type 1 diabetes. They underwent hyperinsulinemic-normoglycemic clamps with [6,6-(2)H2]glucose to assess whole-body and hepatic insulin sensitivity. Hepatic γATP, inorganic phosphate (Pi), and triglyceride concentrations (hepatocellular lipid content [HCL]) were measured with multinuclei magnetic resonance spectroscopy ((31)P/(1)H-MRS). Glucose-tolerant humans served as control (CON) (n = 57). Whole-body insulin sensitivity was 44% lower in patients than in age- and BMI-matched CON. Hepatic γATP was 15% reduced (2.3 ± 0.6 vs. 2.7 ± 0.6 mmol/L, P < 0.001), whereas hepatic Pi and HCL were similar in patients when compared with CON. Across all participants, hepatic γATP correlated negatively with glycemia and oxidized LDL. Carriers of the PPARG G allele (rs1801282) and noncarriers of PPARGC1A A allele (rs8192678) had 21 and 13% lower hepatic ATP concentrations. Variations in genes controlling oxidative metabolism contribute to a reduction in hepatic ATP in the absence of NAFLD, suggesting that alterations in hepatic mitochondrial function may precede diabetes-related liver diseases. [ABSTRACT FROM AUTHOR] |
| Databáze: | Complementary Index |
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