Altered Glucose Uptake in Muscle, Visceral Adipose Tissue, and Brain Predict Whole-Body Insulin Resistance and may Contribute to the Development of Type 2 Diabetes: A Combined PET/MR Study

Hormone and Metabolic Research - Tập 50 Số 08 - Trang 627-639 - 2018
Gretha J. Boersma1, Emil Johansson2, Maria J. Pereira1, Kerstin Heurling2,3, Stanko Skrtic4,5, Joey Lau6,1, Petros Katsogiannos1, Grigorios Panagiotou1, Mark Lubberink2, Joel Kullberg7,2, Håkan Åhlström7,2, Jan W. Eriksson1
1Department of Medical Science, Clinical Diabetes and Metabolism, Uppsala University, Uppsala, Sweden
2Department of Surgical Sciences, Radiology, Uppsala University, Uppsala, Sweden
3Wallenberg Centre for Molecular and Translational Medicine and the Department of Psychiatry and Neurochemistry, University of Gothenburg, Sweden
4AstraZeneca R & D, Gothenburg, Sweden
5Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
6Department of Medical Cell Biology, Uppsala University, Uppsala, Sweden
7Antaros Medical, Mölndal, Sweden

Tóm tắt

AbstractWe assessed glucose uptake in different tissues in type 2 diabetes (T2D), prediabetes, and control subjects to elucidate its impact in the development of whole-body insulin resistance and T2D. Thirteen T2D, 12 prediabetes, and 10 control subjects, matched for age and BMI, underwent OGTT and abdominal subcutaneous adipose tissue (SAT) biopsies. Integrated whole-body 18F-FDG PET and MRI were performed during a hyperinsulinemic euglycemic clamp to asses glucose uptake rate (MRglu) in several tissues. MRglu in skeletal muscle, SAT, visceral adipose tissue (VAT), and liver was significantly reduced in T2D subjects and correlated positively with M-values (r=0.884, r=0.574, r=0.707 and r=0.403, respectively). Brain MRglu was significantly higher in T2D and prediabetes subjects and had a significant inverse correlation with M-values (r=–0.616). Myocardial MRglu did not differ between groups and did not correlate with the M-values. A multivariate model including skeletal muscle, brain and VAT MRglu best predicted the M-values (adjusted r2=0.85). In addition, SAT MRglu correlated with SAT glucose uptake ex vivo (r=0.491). In different stages of the development of T2D, glucose uptake during hyperinsulinemia is elevated in the brain in parallel with an impairment in peripheral organs. Impaired glucose uptake in skeletal muscle and VAT together with elevated glucose uptake in brain were independently associated with whole-body insulin resistance, and these tissue-specific alterations may contribute to T2D development.

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Hormone and Metabolic Research

Tập 50 Số 08

627-639

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