Yonsei Med J.  2008 Dec;49(6):1008-1016. 10.3349/ymj.2008.49.6.1008.

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

• Park MJ
• Jung SR
• Jung HL
• Craig BW
• Lee CD
• Kang HY

• KMID: 1782951
• DOI: http://doi.org/10.3349/ymj.2008.49.6.1008

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 (130microgram/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.

Keyword

Growth hormone; triglyceride content; ceramide; glucose transport rate; insulin resistance

MeSH Terms

Animals
Ceramides/metabolism
Glucose/metabolism
Glucose Transporter Type 4/metabolism
Human Growth Hormone/*administration & dosage
Humans
*Insulin Resistance
Male
Muscle, Skeletal/*drug effects/*metabolism
Rats
Rats, Sprague-Dawley
Recombinant Proteins/administration & dosage
Triglycerides/metabolism

Figure

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  Fig. 1 Change in body weight over 2-day intervals. CON, control group; GH, growth hormone group.

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  Fig. 2 Effect of growth hormone administration on plasma glucose (A) and insulin (B) concentrations during OGTT. CON, control group; GH, growth hormone group; OGTT, oral glucose tolerance test. Each point represents the mean ± SE. *p < 0.05.

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  Fig. 3 GLUT-4 contents in red garstrocnemius (RG) (A) and white garstrocnemius (WG) (B) muscle. CON, control group; GH, growth hormone group. Each point represents the mean ± SE.

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  Fig. 4 Triglyceride contents in plantaris muscle (A) and liver (B). CON, control group; GH, growth hormone group. Each point represents the mean ± SE. *p < 0.05.

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  Fig. 5 Ceramide contents in garstrocnemius muscle . CON, control group; GH, growth hormone group. Each point represents the mean ± SE. *p < 0.05.

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  Fig. 6 Glucose transport rate in epitrochlearis muscle with non- (B) and submaximal insulin conditions (A). CON, control group; GH, growth hormone group. Each point represents the mean ± SE. *p < 0.05.

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  Fig. 7 Correlation between glucose transport rate and muscle TG content under submaximal insulin concentrations. TG, triglyceride.

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