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The effect of human growth hormone on metabolism in healthy volunteers given a normal diet
z_! ‘P $ 0.05
f! 52+13 177’61+ 55+14 152?39+ vs respectwe control;
We conclude that IGF-1 administration after surgery improves whole-body protein metabolism and that 4 mg/kg/day of IGF-1 seems to be the most effective dose in this setting.
Insulin (;lU/ml) C i73f56 i72fi9 351+72+ 210+35 227+88 188t76 246kl5 285+40+ YS respective 8as1c diet
GH (uTg/L)
Basic ORN
‘25f6 190+54+ 41*10 139+49+ + P $ 0.05
N retention after trauma is significantly (P < 0.05) more (48+3%) with OKG than with ORN (31+5) or with OKIC (36+2%) or with Basic diet (39+4%). Hormonal effects of ORN and the synergistic metabolic effects of a ketoglutarate may be combined in rats for the anabolic nature of OKG. P.74
P.75 The effect of human growth hormone on metabolism in healthy volunteers given a normal diet.
T. Inaba. H. Saito. M. Lin, T. lnoue, Y. Hashiguchi. R. Fukushima and 7. Muto Department of Surgery, University of Tokyo, Tokyo, Japan
A. Sandgren, P. Es&n, K. Andersson. J. Wernerman Dept. of Anesthesiology & Intensive Care and Metabolic Research Laboratory St. Gbrans Hospital and Dept of Anesthesiology & Intensive Care Huddinge University Hospital, Stockholm, Sweden
Titration of insulin-like growth factor-l dosage that maximises anabolic effects in rats after gastrectomy.
Insulin-like growth factor-l (IGF-1) has been shown to improve nitrogen metabolism after surgical trauma in rats. However, the most effective dose of IGF-1 has not been well known in surgical models. The purpose of this study was to identify the appropriate dose of IG F-l on nitrogen metabolism in rats after gastrectomy. Thirty-two rats received total parenteral nutrition (200 kcal/kg/day and 0.99 gN/kg/day) after gastrectomy. Continuous intravenous infusions of 1, 2 or 4 mg/kg/day of IGF-1 or placebo were also given for 3 postoperative days. Whole-body protein turnover and fractional synthesis rate (FSR) of tissue protein were determined using 15 N-glycine constant infusion method on postoperative day 3. Results were statistically analyzed using analysis of variance. Nitrogen Excretion (mglkgldw) Natrogen Balance (mglkgldw) Whole Body Protein (gN/kgfdw) Synthesis (gN/kg/dwl Breakdown (gN/kgldw Synthesis/Breakdown (%) Liver FSR Ga??$&i)mius (%/day)
Control 1009+101 -33Ok98
IGF-1
Introduction: Earlier studies have shown that exogenous human growth hormone (hGH) has effects on protein, fat and glucose metabolism in patients. However the effects of hGH on metabolism in normal man given a normocaloric normonitrogenous diet is unclear. The aim of this study was to evaluate the effects on nitrogen balance and serum concentrations of hormones and metabolites in healthy volunteers, given a daily subcutaneous injection of hGH. Methods: Healthy male volunteers (n = 15) were given a standardised diet as 4 daily meals during a period of 8 days. Their individual basal energy expenditure was measured with indirect calorimetry, and they received 150% of the measured caloric value. Days l-2 was a conditioning period. On days 3-8 half of the group (n = 8) received a subcutaneus injection with hGH (Genotropin) 0.3 E/kg/24 h and the other half (n = 7) a subcutaneus saline injection. Blood samples were taken daily before food intake for analyses of the concentration of urea, glucose, insulin and triglycerides. The total urinary nitrogen excretion was determined in 24 h portions. The results show significant changes in serum concentrations of urea, glucose, insulin, and triglycerides before and after 6 days of daily hGH-injections compared to the control group. In the hGH-group there was a decrease in serum urea (mmol/l) from 5.OkO.3 to 2.5kO.3 compared to 5410.4 to 5.310.3 in the control group. The total nitrogen excretion (g) in urine declined from ?2.4& 1.4 to 6.750.8 in the hGHgroup compared to the controls 12.0+ 1 .Ito 11.5& 0.6. The glucose level (mmol/l) rose from 5.2kO.3 to 5.8+0.1 (hGHgroup) compared to 4.8kO.2 to 5.520.4. Insulin (@J/l) increased from 6.9+0.8 to 20.2k3.4 (hGH) and was unchanged in the controls 6.6kl.8 to 7.4k2.2. The triglycerides increased from 1.1 10.1 to 1.5+0.1 (hGH) and was unchanged in the control group 1 .I kO.2 to 0.9+0.2. Conclusion: In normal man a daily dose of hGH for 6 days makes whole body nitrogen economy 50% more effective. In addition hyperlipidemia. hyperinsulinemia and hyperglycemia were seen.
1 mg
812+79 -138k80
Flux 3.64 i 0.24
4.01 ir0 36
2.60 t_ 0.24
3.1010
2.61 kO.24
3.00 i_ 0.36
lOOk4
103+5
15.0+1.6
17.3+0.8
39
FSR 1.34+0.09 IGF-1
Nitrogen Excretion (mglkgldav) Nitrogen Balance (mglkgldw) Whole Body Protein (gN/kg/day) Synthesis (gN/kg/dw) Breakdown (gN/kg/dw) Synthesis/Breakdown
769*
1.26iOO9 2 mg
93”
-99+84”
4 mg
61 +41’
Flux 4.04+0.17
4.79+0
38’
3.19tO.18
4.24+0
39’
3.04*0.15
3.81 +O 3’
105*4 L,zFSR (%/dw) Gastrocnemius FSR (%/day) Mean+SE ‘p < 0.01
IGF-1 595*41*
17.0fl
YS control
*‘p
112+2** 2
15.9*1.4
1.44+0.08 1.24*0.09 < 0 05 vs control
57
f! 52+13 177’61+ 55+14 152?39+ vs respectwe control;
We conclude that IGF-1 administration after surgery improves whole-body protein metabolism and that 4 mg/kg/day of IGF-1 seems to be the most effective dose in this setting.
Insulin (;lU/ml) C i73f56 i72fi9 351+72+ 210+35 227+88 188t76 246kl5 285+40+ YS respective 8as1c diet
GH (uTg/L)
Basic ORN
‘25f6 190+54+ 41*10 139+49+ + P $ 0.05
N retention after trauma is significantly (P < 0.05) more (48+3%) with OKG than with ORN (31+5) or with OKIC (36+2%) or with Basic diet (39+4%). Hormonal effects of ORN and the synergistic metabolic effects of a ketoglutarate may be combined in rats for the anabolic nature of OKG. P.74
P.75 The effect of human growth hormone on metabolism in healthy volunteers given a normal diet.
T. Inaba. H. Saito. M. Lin, T. lnoue, Y. Hashiguchi. R. Fukushima and 7. Muto Department of Surgery, University of Tokyo, Tokyo, Japan
A. Sandgren, P. Es&n, K. Andersson. J. Wernerman Dept. of Anesthesiology & Intensive Care and Metabolic Research Laboratory St. Gbrans Hospital and Dept of Anesthesiology & Intensive Care Huddinge University Hospital, Stockholm, Sweden
Titration of insulin-like growth factor-l dosage that maximises anabolic effects in rats after gastrectomy.
Insulin-like growth factor-l (IGF-1) has been shown to improve nitrogen metabolism after surgical trauma in rats. However, the most effective dose of IGF-1 has not been well known in surgical models. The purpose of this study was to identify the appropriate dose of IG F-l on nitrogen metabolism in rats after gastrectomy. Thirty-two rats received total parenteral nutrition (200 kcal/kg/day and 0.99 gN/kg/day) after gastrectomy. Continuous intravenous infusions of 1, 2 or 4 mg/kg/day of IGF-1 or placebo were also given for 3 postoperative days. Whole-body protein turnover and fractional synthesis rate (FSR) of tissue protein were determined using 15 N-glycine constant infusion method on postoperative day 3. Results were statistically analyzed using analysis of variance. Nitrogen Excretion (mglkgldw) Natrogen Balance (mglkgldw) Whole Body Protein (gN/kgfdw) Synthesis (gN/kg/dwl Breakdown (gN/kgldw Synthesis/Breakdown (%) Liver FSR Ga??$&i)mius (%/day)
Control 1009+101 -33Ok98
IGF-1
Introduction: Earlier studies have shown that exogenous human growth hormone (hGH) has effects on protein, fat and glucose metabolism in patients. However the effects of hGH on metabolism in normal man given a normocaloric normonitrogenous diet is unclear. The aim of this study was to evaluate the effects on nitrogen balance and serum concentrations of hormones and metabolites in healthy volunteers, given a daily subcutaneous injection of hGH. Methods: Healthy male volunteers (n = 15) were given a standardised diet as 4 daily meals during a period of 8 days. Their individual basal energy expenditure was measured with indirect calorimetry, and they received 150% of the measured caloric value. Days l-2 was a conditioning period. On days 3-8 half of the group (n = 8) received a subcutaneus injection with hGH (Genotropin) 0.3 E/kg/24 h and the other half (n = 7) a subcutaneus saline injection. Blood samples were taken daily before food intake for analyses of the concentration of urea, glucose, insulin and triglycerides. The total urinary nitrogen excretion was determined in 24 h portions. The results show significant changes in serum concentrations of urea, glucose, insulin, and triglycerides before and after 6 days of daily hGH-injections compared to the control group. In the hGH-group there was a decrease in serum urea (mmol/l) from 5.OkO.3 to 2.5kO.3 compared to 5410.4 to 5.310.3 in the control group. The total nitrogen excretion (g) in urine declined from ?2.4& 1.4 to 6.750.8 in the hGHgroup compared to the controls 12.0+ 1 .Ito 11.5& 0.6. The glucose level (mmol/l) rose from 5.2kO.3 to 5.8+0.1 (hGHgroup) compared to 4.8kO.2 to 5.520.4. Insulin (@J/l) increased from 6.9+0.8 to 20.2k3.4 (hGH) and was unchanged in the controls 6.6kl.8 to 7.4k2.2. The triglycerides increased from 1.1 10.1 to 1.5+0.1 (hGH) and was unchanged in the control group 1 .I kO.2 to 0.9+0.2. Conclusion: In normal man a daily dose of hGH for 6 days makes whole body nitrogen economy 50% more effective. In addition hyperlipidemia. hyperinsulinemia and hyperglycemia were seen.
1 mg
812+79 -138k80
Flux 3.64 i 0.24
4.01 ir0 36
2.60 t_ 0.24
3.1010
2.61 kO.24
3.00 i_ 0.36
lOOk4
103+5
15.0+1.6
17.3+0.8
39
FSR 1.34+0.09 IGF-1
Nitrogen Excretion (mglkgldav) Nitrogen Balance (mglkgldw) Whole Body Protein (gN/kg/day) Synthesis (gN/kg/dw) Breakdown (gN/kg/dw) Synthesis/Breakdown
769*
1.26iOO9 2 mg
93”
-99+84”
4 mg
61 +41’
Flux 4.04+0.17
4.79+0
38’
3.19tO.18
4.24+0
39’
3.04*0.15
3.81 +O 3’
105*4 L,zFSR (%/dw) Gastrocnemius FSR (%/day) Mean+SE ‘p < 0.01
IGF-1 595*41*
17.0fl
YS control
*‘p
112+2** 2
15.9*1.4
1.44+0.08 1.24*0.09 < 0 05 vs control
57