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The effect of growth hormone (GH) on intramyocellular (IMCL), intrahepatic lipids (IHCL) and visceral fat mass in relation to insulin resistance

English title The effect of growth hormone (GH) on intramyocellular (IMCL), intrahepatic lipids (IHCL) and visceral fat mass in relation to insulin resistance
Applicant Christ Emanuel
Number 109522
Funding scheme Project funding (Div. I-III)
Research institution Poliklinik für Endokrinologie, Diabetologie und Klinische Ernährung Inselspital
Institution of higher education University of Berne - BE
Main discipline Clinical Endocrinology
Start/End 01.04.2006 - 31.08.2010
Approved amount 227'772.00
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Keywords (6)

GH; GH-deficiency; type 1 diabetes; endurance trained athletes; magnetic resonance spectroscopy; visceral fat mass

Lay Summary (English)

Lead
Lay summary
Background: Besides visceral fat mass an increase in lipid content in non-adipose tissues (“ectopic”) such as skeletal muscle (i.e. myocytes; IMCL), liver cells (i.e.hepatocytes; IHCL) and visceral fat mass (fat tissue in the abdomen) has been implicated in impaired insulin action. Body fat accumulation depend on diet and physical activity.Growth hormone (GH) modulates exercise capacity and metabolism. GH secretion increases with exercise and GH promotes lipolysis. This may impact on “ectopic” lipid accumulation, thereby modulating insulin action.Adult hypopituitarism with GH-deficiency is related to insulin resistance. By replacing GH in GH-deficient patients the metabolic role of GH on “ectopic” lipid stores in relation to insulin resistance can be examined. Working Hypothesis: “Ectopic” fat deposition and visceral fat mass interfere with insulin action. Physical activity and diet impact on lipid stores. GH modulates “ectopic” lipid stores, thereby altering insulin action.Specific Aims: To investigate the role of diet and exercise on visceral fat mass and “ectopic” fat deposition (IMCL, IHCL) in relation to hepatic (i.e. liver) and peripheral (i.e. skeletal muscle) insulin action in patients with adult GH-deficiency, control subjects (sedentary and insulin sensitive, endurance trained athletes). To examine the role of GH replacement on “ectopic” fat stores in patients with adult GH-deficiency in relation to peripheral and hepatic insulin resistance. Experimental Design and Methods: Using magnetic resonance spectroscopy we intend to investigate IMCL and IHCL content under standardised conditions (diet and physical activity) in control subjects and in patients (with adult GH-deficiency) before and after GH replacement therapy. Visceral fat mass will be assessed by magnetic resonance imaging. Insulin action will be measured by a two step hyperinsulinaemic, euglycaemic clamp combined with stable isotope technique (not radioactive tracer technique measuring glucose turnover).Expected Value: 1) The results of this study will give insight into the effects of diet and physical activity on “ectopic” fat stores in relation to insulin resistance in patients and healthy subjects.2)Therapeutical intervention in patients with GH-deficiency (GH replacement therapy) will allow to better define the role of GH on “ectopic” fat stores relative to insulin resistance.3)These data will further enhance our understanding of the regulatory function of GH on insulin resistance and allow to extend our investigations to other endocrine disorders which are associated with insulin resistance.
Direct link to Lay Summary Last update: 21.02.2013

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