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      Insulin-stimulated glucose uptake in skeletal muscle, adipose tissue and liver: a positron emission tomography study

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          Abstract

          Objective

          Insulin resistance is reflected by the rates of reduced glucose uptake (GU) into the key insulin-sensitive tissues, skeletal muscle, liver and adipose tissue. It is unclear whether insulin resistance occurs simultaneously in all these tissues or whether insulin resistance is tissue specific.

          Design and methods

          We measured GU in skeletal muscle, adipose tissue and liver and endogenous glucose production (EGP), in a single session using 18F-fluorodeoxyglucose with positron emission tomography (PET) and euglycemic–hyperinsulinemic clamp. The study population consisted of 326 subjects without diabetes from the CMgene study cohort.

          Results

          Skeletal muscle GU less than 33 µmol/kg tissue/min and subcutaneous adipose tissue GU less than 11.5 µmol/kg tissue/min characterized insulin-resistant individuals. Men had considerably worse insulin suppression of EGP compared to women. By using principal component analysis (PCA), BMI inversely and skeletal muscle, adipose tissue and liver GU positively loaded on same principal component explaining one-third of the variation in these measures. The results were largely similar when liver GU was replaced by EGP in PCA. Liver GU and EGP were positively associated with aging.

          Conclusions

          We have provided threshold values, which can be used to identify tissue-specific insulin resistance. In addition, we found that insulin resistance measured by GU was only partially similar across all insulin-sensitive tissues studied, skeletal muscle, adipose tissue and liver and was affected by obesity, aging and gender.

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          Most cited references28

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          Glucose clamp technique: a method for quantifying insulin secretion and resistance.

          Methods for the quantification of beta-cell sensitivity to glucose (hyperglycemic clamp technique) and of tissue sensitivity to insulin (euglycemic insulin clamp technique) are described. Hyperglycemic clamp technique. The plasma glucose concentration is acutely raised to 125 mg/dl above basal levels by a priming infusion of glucose. The desired hyperglycemic plateau is subsequently maintained by adjustment of a variable glucose infusion, based on the negative feedback principle. Because the plasma glucose concentration is held constant, the glucose infusion rate is an index of glucose metabolism. Under these conditions of constant hyperglycemia, the plasma insulin response is biphasic with an early burst of insulin release during the first 6 min followed by a gradually progressive increase in plasma insulin concentration. Euglycemic insulin clamp technique. The plasma insulin concentration is acutely raised and maintained at approximately 100 muU/ml by a prime-continuous infusion of insulin. The plasma glucose concentration is held constant at basal levels by a variable glucose infusion using the negative feedback principle. Under these steady-state conditions of euglycemia, the glucose infusion rate equals glucose uptake by all the tissues in the body and is therefore a measure of tissue sensitivity to exogenous insulin.
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            Diagnosis and classification of diabetes mellitus.

            (2006)
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              Liver, muscle, and adipose tissue insulin action is directly related to intrahepatic triglyceride content in obese subjects.

              Nonalcoholic fatty liver disease is associated with insulin resistance and diabetes. The purpose of this study was to determine the relationship between intrahepatic triglyceride (IHTG) content and insulin action in liver (suppression of glucose production), skeletal muscle (stimulation of glucose uptake), and adipose tissue (suppression of lipolysis) in nondiabetic obese subjects. A euglycemic-hyperinsulinemic clamp procedure and stable isotopically labeled tracer infusions were used to assess insulin action, and magnetic resonance spectroscopy was used to determine IHTG content, in 42 nondiabetic obese subjects (body mass index, 36 +/- 4 kg/m(2)) who had a wide range of IHTG content (1%-46%). Hepatic insulin sensitivity, assessed as a function of glucose production rate and plasma insulin concentration, was inversely correlated with IHTG content (r = -0.599; P < .001). The ability of insulin to suppress fatty acid release from adipose tissue and to stimulate glucose uptake by skeletal muscle were also inversely correlated with IHTG content (adipose tissue: r = -0.590, P < .001; skeletal muscle: r = -0.656, P < .001). Multivariate linear regression analyses found that IHTG content was the best predictor of insulin action in liver, skeletal muscle, and adipose tissue, independent of body mass index and percent body fat, and accounted for 34%, 42%, and 44% of the variability in these tissues, respectively (P < .001 for each model). These results show that progressive increases in IHTG content are associated with progressive impairment of insulin action in liver, skeletal muscle, and adipose tissue in nondiabetic obese subjects. Therefore, nonalcoholic fatty liver disease should be considered part of a multiorgan system derangement in insulin sensitivity.
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                Author and article information

                Journal
                Eur J Endocrinol
                Eur. J. Endocrinol
                EJE
                European Journal of Endocrinology
                Bioscientifica Ltd (Bristol )
                0804-4643
                1479-683X
                May 2018
                07 March 2018
                : 178
                : 5
                : 523-531
                Affiliations
                [1 ]Turku PET Centre, University of Turku Turku, Finland
                [2 ]Turku PET Centre, Åbo Akademi University Turku, Finland
                [3 ]Turku PET Centre, Institute of Public Health and Clinical Nutrition University of Eastern Finland, Kuopio, Finland
                [4 ]Department of Endocrinology Turku University Hospital, Turku, Finland
                Author notes
                Correspondence should be addressed to P Nuutila; Email: pirjo.nuutila@ 123456utu.fi
                Article
                EJE170882
                10.1530/EJE-17-0882
                5920018
                29535167
                338ad708-1483-4a63-90a5-23a616460e38
                © 2018 The authors

                This work is licensed under a Creative Commons Attribution 4.0 International License.

                History
                : 24 October 2017
                : 12 March 2018
                Categories
                Clinical Study

                Endocrinology & Diabetes
                Endocrinology & Diabetes

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