Maria Fritsch1, Chrysi Koliaki2, Roshan Livingstone3, Esther Phielix3, Alessandra Bierwagen4, Markus Meisinger3, Tomas Jelenik4, Klaus Strassburger5, Stefanie Zimmermann4, Katharina Brockmann4, Christina Wolff4, Jong-Hee Hwang4, Julia Szendroedi2, Michael Roden6. 1. Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research, Department of Pediatric and Adolescent Medicine, Medical University of Vienna, Vienna, Austria; and. 2. Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research, Department of Endocrinology and Diabetology, Medical Faculty, and German Center of Diabetes Research, Partner Düsseldorf, Germany. 3. Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research. 4. Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research, German Center of Diabetes Research, Partner Düsseldorf, Germany. 5. Institute for Biometrics and Epidemiology, German Diabetes Center, Leibniz Center for Diabetes Research, Heinrich-Heine University, Düsseldorf, Germany, German Center of Diabetes Research, Partner Düsseldorf, Germany. 6. Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research, Department of Endocrinology and Diabetology, Medical Faculty, and German Center of Diabetes Research, Partner Düsseldorf, Germany michael.roden@ddz.uni-duesseldorf.de.
Abstract
BACKGROUND: Impaired energy metabolism is a possible mechanism that contributes to insulin resistance and ectopic fat storage. OBJECTIVE: We examined whether meal ingestion differently affects hepatic phosphorus metabolites in insulin-sensitive and insulin-resistant humans. DESIGN: Young, lean, insulin-sensitive humans (CONs) [mean ± SD body mass index (BMI; in kg/m(2)): 23.2 ± 1.5]; insulin-resistant, glucose-tolerant, obese humans (OBEs) (BMI: 34.3 ± 1.7); and type 2 diabetes patients (T2Ds) (BMI: 32.0 ± 2.4) were studied (n = 10/group). T2Ds (61 ± 7 y old) were older (P < 0.001) than were OBEs (31 ± 7 y old) and CONs (28 ± 3 y old). We quantified hepatic γATP, inorganic phosphate (Pi), and the fat content [hepatocellular lipids (HCLs)] with the use of (31)P/(1)H magnetic resonance spectroscopy before and at 160 and 240 min after a high-caloric mixed meal. In a subset of volunteers, we measured the skeletal muscle oxidative capacity with the use of high-resolution respirometry. Whole-body insulin sensitivity (M value) was assessed with the use of hyperinsulinemic-euglycemic clamps. RESULTS: OBEs and T2Ds were similarly insulin resistant (M value: 3.5 ± 1.4 and 1.9 ± 2.5 mg · kg(-1) · min(-1), respectively; P = 0.9) and had 12-fold (P = 0.01) and 17-fold (P = 0.002) higher HCLs, respectively, than those of lean persons. Despite comparable fasting hepatic γATP concentrations, the maximum postprandial increase of γATP was 6-fold higher in OBEs (0.7 ± 0.2 mmol/L; P = 0.03) but only tended to be higher in T2Ds (0.6 ± 0.2 mmol/L; P = 0.09) than in CONs (0.1 ± 0.1 mmol/L). However, in the fasted state, muscle complex I activity was 53% lower (P = 0.01) in T2Ds but not in OBEs (P = 0.15) than in CONs. CONCLUSIONS: Young, obese, nondiabetic humans exhibit augmented postprandial hepatic energy metabolism, whereas elderly T2Ds have impaired fasting muscle energy metabolism. These findings support the concept of a differential and tissue-specific regulation of energy metabolism, which can occur independently of insulin resistance. This trial was registered at clinicaltrials.gov as NCT01229059.
BACKGROUND: Impaired energy metabolism is a possible mechanism that contributes to insulin resistance and ectopic fat storage. OBJECTIVE: We examined whether meal ingestion differently affects hepatic phosphorus metabolites in insulin-sensitive and insulin-resistant humans. DESIGN: Young, lean, insulin-sensitive humans (CONs) [mean ± SD body mass index (BMI; in kg/m(2)): 23.2 ± 1.5]; insulin-resistant, glucose-tolerant, obesehumans (OBEs) (BMI: 34.3 ± 1.7); and type 2 diabetespatients (T2Ds) (BMI: 32.0 ± 2.4) were studied (n = 10/group). T2Ds (61 ± 7 y old) were older (P < 0.001) than were OBEs (31 ± 7 y old) and CONs (28 ± 3 y old). We quantified hepatic γATP, inorganic phosphate (Pi), and the fat content [hepatocellular lipids (HCLs)] with the use of (31)P/(1)H magnetic resonance spectroscopy before and at 160 and 240 min after a high-caloric mixed meal. In a subset of volunteers, we measured the skeletal muscle oxidative capacity with the use of high-resolution respirometry. Whole-body insulin sensitivity (M value) was assessed with the use of hyperinsulinemic-euglycemic clamps. RESULTS: OBEs and T2Ds were similarly insulin resistant (M value: 3.5 ± 1.4 and 1.9 ± 2.5 mg · kg(-1) · min(-1), respectively; P = 0.9) and had 12-fold (P = 0.01) and 17-fold (P = 0.002) higher HCLs, respectively, than those of lean persons. Despite comparable fasting hepatic γATP concentrations, the maximum postprandial increase of γATP was 6-fold higher in OBEs (0.7 ± 0.2 mmol/L; P = 0.03) but only tended to be higher in T2Ds (0.6 ± 0.2 mmol/L; P = 0.09) than in CONs (0.1 ± 0.1 mmol/L). However, in the fasted state, muscle complex I activity was 53% lower (P = 0.01) in T2Ds but not in OBEs (P = 0.15) than in CONs. CONCLUSIONS: Young, obese, nondiabetic humans exhibit augmented postprandial hepatic energy metabolism, whereas elderly T2Ds have impaired fasting muscle energy metabolism. These findings support the concept of a differential and tissue-specific regulation of energy metabolism, which can occur independently of insulin resistance. This trial was registered at clinicaltrials.gov as NCT01229059.
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