25
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Effects of 4 Weeks Recombinant Human Growth Hormone Administration on Insulin Resistance of Skeletal Muscle in Rats

      research-article

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Purpose

          Effect of recombinant human growth hormone (rhGH) administration on lipid storage, and its subsequent effect on insulin sensitivity have not yet been adequately examined. Thus, we investigated the effects of rhGH treatment on muscle triglyceride (TG) and ceramide content, and insulin sensitivity after 4 weeks of rhGH administration in rats.

          Materials and Methods

          Fourteen rats were randomly assigned to two groups: rhGH injection group (GH, n = 7) and saline injection group (CON, n = 7). GH received rhGH by subcutaneous injections (130 µg·kg -1·day -1, 6 days·week -1) for 4 weeks, while CON received saline injections that were equivalent in volume to GH group. Intramuscular TG and ceramide content and hepatic TG content were measured. To determine insulin sesitivity, oral glucose tolerance test (OGTT) and muscle incubation for glucose transport rate were performed in rats, and used as indicators of insulin sensitivity. We also examined plasm lipid profiles.

          Results

          After 4 weeks of rhGH treatment, the GH group had higher muscle and liver TG contents than the CON ( p < 0.05). Ceramide content in GH was significantly greater than that in CON ( p < 0.05). GH also had higher plasma levels of FFA ( p < 0.05), glucose and insulin responses during OGTT ( p < 0.05), and lower glucose transport rates in submaximal insulin concentration ( p < 0.05) as compared with CON. Results indicate that rhGH treatment is associated with insulin resistance in rats.

          Conclusion

          rhGH treatment elevated muscle TG and ceramide content, and hepatic TG content. Thus, elevation of these compounde by rhGH treatment could contribute to the development of insulin resistance in rats.

          Related collections

          Most cited references41

          • Record: found
          • Abstract: found
          • Article: not found

          Ceramides in insulin resistance and lipotoxicity.

          S. Summers (2006)
          Obesity predisposes individuals to the development of insulin resistance in skeletal muscle and the liver, and researchers have recently proposed two mechanisms by which excess adiposity antagonizes insulin action in peripheral tissues. First, when adipocytes exceed their storage capacity, fat begins to accumulate in tissues not suited for lipid storage, leading to the formation of specific metabolites that inhibit insulin signal transduction. Second, obesity triggers a chronic inflammatory state, and cytokines released from either adipocytes or from macrophages infiltrating adipose tissue antagonize insulin action. The sphingolipid ceramide is a putative intermediate linking both excess nutrients (i.e. saturated fatty acids) and inflammatory cytokines (e.g. tumor necrosis factor-alpha, TNFalpha) to the induction of insulin resistance. Moreover, ceramide has been shown to be toxic in a variety of different cell types (e.g. pancreatic beta-cells, cardiomyocytes, etc.), and review of the literature reveals putative roles for the sphingolipid in the damage of cells and tissues which accompany diabetes, hypertension, cardiac failure, atherosclerosis, etc. In this review, I will evaluate the contribution of ceramides in the development of insulin resistance and the complications associated with metabolic diseases.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Overproduction of large VLDL particles is driven by increased liver fat content in man.

            We determined whether hepatic fat content and plasma adiponectin concentration regulate VLDL(1) production. A multicompartment model was used to simultaneously determine the kinetic parameters of triglycerides (TGs) and apolipoprotein B (ApoB) in VLDL(1) and VLDL(2) after a bolus of [(2)H(3)]leucine and [(2)H(5)]glycerol in ten men with type 2 diabetes and in 18 non-diabetic men. Liver fat content was determined by proton spectroscopy and intra-abdominal fat content by MRI. Univariate regression analysis showed that liver fat content, intra-abdominal fat volume, plasma glucose, insulin and HOMA-IR (homeostasis model assessment of insulin resistance) correlated with VLDL(1) TG and ApoB production. However, only liver fat and plasma glucose were significant in multiple regression models, emphasising the critical role of substrate fluxes and lipid availability in the liver as the driving force for overproduction of VLDL(1) in subjects with type 2 diabetes. Despite negative correlations with fasting TG levels, liver fat content, and VLDL(1) TG and ApoB pool sizes, adiponectin was not linked to VLDL(1) TG or ApoB production and thus was not a predictor of VLDL(1) production. However, adiponectin correlated negatively with the removal rates of VLDL(1) TG and ApoB. We propose that the metabolic effect of insulin resistance, partly mediated by depressed plasma adiponectin levels, increases fatty acid flux from adipose tissue to the liver and induces the accumulation of fat in the liver. Elevated plasma glucose can further increase hepatic fat content through multiple pathways, resulting in overproduction of VLDL(1) particles and leading to the characteristic dyslipidaemia associated with type 2 diabetes.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Targeted disruption of the glucose transporter 4 selectively in muscle causes insulin resistance and glucose intolerance.

              The prevalence of type 2 diabetes mellitus is growing worldwide. By the year 2020, 250 million people will be afflicted. Most forms of type 2 diabetes are polygenic with complex inheritance patterns, and penetrance is strongly influenced by environmental factors. The specific genes involved are not yet known, but impaired glucose uptake in skeletal muscle is an early, genetically determined defect that is present in non-diabetic relatives of diabetic subjects. The rate-limiting step in muscle glucose use is the transmembrane transport of glucose mediated by glucose transporter (GLUT) 4 (ref. 4), which is expressed mainly in skeletal muscle, heart and adipose tissue. GLUT4 mediates glucose transport stimulated by insulin and contraction/exercise. The importance of GLUT4 and glucose uptake in muscle, however, was challenged by two recent observations. Whereas heterozygous GLUT4 knockout mice show moderate glucose intolerance, homozygous whole-body GLUT4 knockout (GLUT4-null) mice have only mild perturbations in glucose homeostasis and have growth retardation, depletion of fat stores, cardiac hypertrophy and failure, and a shortened life span. Moreover, muscle-specific inactivation of the insulin receptor results in minimal, if any, change in glucose tolerance. To determine the importance of glucose uptake into muscle for glucose homeostasis, we disrupted GLUT4 selectively in mouse muscles. A profound reduction in basal glucose transport and near-absence of stimulation by insulin or contraction resulted. These mice showed severe insulin resistance and glucose intolerance from an early age. Thus, GLUT4-mediated glucose transport in muscle is essential to the maintenance of normal glucose homeostasis.
                Bookmark

                Author and article information

                Journal
                Yonsei Med J
                YMJ
                Yonsei Medical Journal
                Yonsei University College of Medicine
                0513-5796
                1976-2437
                31 December 2008
                31 December 2008
                : 49
                : 6
                : 1008-1016
                Affiliations
                [1 ]Department of Pediatrics, Sanggye Paik Hospital, Inje University School of Medicine, Seoul, Korea.
                [2 ]Department of Physical Education, Kyungpook National University, Daegu, Korea.
                [3 ]Human Performance Laboratory, Ball State University, Muncie, Indiana, USA.
                [4 ]Department of Exercise and Wellness, Arizona State University, Mesa, Arizona, USA.
                Author notes
                Reprint address: requests to Dr. Ho Youl Kang, Department of Physical Education, Kyungpook National University, 1370 Sankyuk-dong, Buk-gu, Daegu 702-701, Korea. Tel: 82-53-950-5944~5, Fax: 82-53-955-4235, hokang62@ 123456hotmail.com
                Article
                10.3349/ymj.2008.49.6.1008
                2628033
                19108026
                bb1cdfd6-e571-4c66-9687-962a47d4cb84
                Copyright © 2008 The Yonsei University College of Medicine

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/3.0) which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 05 February 2008
                : 11 July 2008
                Categories
                Original Article

                Medicine
                growth hormone,glucose transport rate,insulin resistance,ceramide,triglyceride content
                Medicine
                growth hormone, glucose transport rate, insulin resistance, ceramide, triglyceride content

                Comments

                Comment on this article