Abstract
| Originalsprog | Engelsk |
|---|---|
| Tidsskrift | Journal of Clinical Endocrinology and Metabolism |
| Vol/bind | 94 |
| Udgave nummer | 3 |
| Sider (fra-til) | 965-72 |
| Antal sider | 7 |
| ISSN | 0021-972X |
| DOI | |
| Status | Udgivet - 2008 |
Bibliografisk note
Keywords: Adult; C-Peptide; Cross-Over Studies; Fasting; Glucose; Human Growth Hormone; Humans; Insulin; Insulin-Like Growth Factor Binding Protein 1; Insulin-Like Growth Factor I; Janus Kinase 2; Lipid Metabolism; Lipolysis; Male; Metabolic Clearance Rate; Muscle, Skeletal; STAT5 Transcription Factor; Signal TransductionAdgang til dokumentet
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Impact of fasting on growth hormone signaling and action in muscle and fat. / Moller, Louise; Dalman, Lisa; Norrelund, Helene; Billestrup, Nils; Frystyk, Jan; Moller, Niels; Jorgensen, Jens Otto Lunde.
I: Journal of Clinical Endocrinology and Metabolism, Bind 94, Nr. 3, 2008, s. 965-72.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review
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TY - JOUR
T1 - Impact of fasting on growth hormone signaling and action in muscle and fat
AU - Moller, Louise
AU - Dalman, Lisa
AU - Norrelund, Helene
AU - Billestrup, Nils
AU - Frystyk, Jan
AU - Moller, Niels
AU - Jorgensen, Jens Otto Lunde
N1 - Keywords: Adult; C-Peptide; Cross-Over Studies; Fasting; Glucose; Human Growth Hormone; Humans; Insulin; Insulin-Like Growth Factor Binding Protein 1; Insulin-Like Growth Factor I; Janus Kinase 2; Lipid Metabolism; Lipolysis; Male; Metabolic Clearance Rate; Muscle, Skeletal; STAT5 Transcription Factor; Signal Transduction
PY - 2008
Y1 - 2008
N2 - CONTEXT: Whether GH promotes IGF-I production or lipolysis depends on nutritional status, but the underlying mechanisms remain unknown. OBJECTIVE: To investigate the impact of fasting on GH-mediated changes in substrate metabolism, insulin sensitivity, and signaling pathways. DESIGN: We conducted a randomized crossover study. SUBJECTS: Ten healthy men (age 24.3 +/- 0.6 yr, body mass index 23.1 +/- 0.4 kg/m(2)) participated. INTERVENTION: A GH bolus administered 1) postabsorptively and 2) in the fasting state (37.5 h). Skeletal muscle and adipose tissue biopsies were taken, and a hyperinsulinemic-euglycemic clamp was performed on both occasions. MAIN OUTCOME MEASURES: Metabolic clearance rate (MCR) of GH, substrate metabolism, and insulin sensitivity were measured. Biopsies were subjected to Western blotting for expression of signaling proteins and to RT-PCR for expression of suppressor of cytokine signaling protein 3 and IGF-I mRNA. RESULTS: Fasting was associated with reduced MCR of GH (P < 0.01), enhanced lipolytic responsiveness to GH, decreased insulin sensitivity (P < 0.01), and reduced IGF-I bioactivity (P = 0.04). After the GH bolus, phosphorylation of signal transducers and activators of transcription protein 5b (pSTAT5b) were observed in both conditions; however, the phospho-STAT5b/STAT5b ratio was significantly decreased in the fasting state (muscle P = 0.02 and fat P = 0.02). CONCLUSION: The combination of fasting and GH exposure translates into enhanced lipolysis, reduced IGF-I activity and insulin sensitivity, and blunted activation of the Janus kinase (JAK)/STAT pathway. Whether this change in signaling activity is related to the change in MCR of GH and/or the concomitant shift in the metabolic effects of GH merits future attention.
AB - CONTEXT: Whether GH promotes IGF-I production or lipolysis depends on nutritional status, but the underlying mechanisms remain unknown. OBJECTIVE: To investigate the impact of fasting on GH-mediated changes in substrate metabolism, insulin sensitivity, and signaling pathways. DESIGN: We conducted a randomized crossover study. SUBJECTS: Ten healthy men (age 24.3 +/- 0.6 yr, body mass index 23.1 +/- 0.4 kg/m(2)) participated. INTERVENTION: A GH bolus administered 1) postabsorptively and 2) in the fasting state (37.5 h). Skeletal muscle and adipose tissue biopsies were taken, and a hyperinsulinemic-euglycemic clamp was performed on both occasions. MAIN OUTCOME MEASURES: Metabolic clearance rate (MCR) of GH, substrate metabolism, and insulin sensitivity were measured. Biopsies were subjected to Western blotting for expression of signaling proteins and to RT-PCR for expression of suppressor of cytokine signaling protein 3 and IGF-I mRNA. RESULTS: Fasting was associated with reduced MCR of GH (P < 0.01), enhanced lipolytic responsiveness to GH, decreased insulin sensitivity (P < 0.01), and reduced IGF-I bioactivity (P = 0.04). After the GH bolus, phosphorylation of signal transducers and activators of transcription protein 5b (pSTAT5b) were observed in both conditions; however, the phospho-STAT5b/STAT5b ratio was significantly decreased in the fasting state (muscle P = 0.02 and fat P = 0.02). CONCLUSION: The combination of fasting and GH exposure translates into enhanced lipolysis, reduced IGF-I activity and insulin sensitivity, and blunted activation of the Janus kinase (JAK)/STAT pathway. Whether this change in signaling activity is related to the change in MCR of GH and/or the concomitant shift in the metabolic effects of GH merits future attention.
U2 - 10.1210/jc.2008-1385
DO - 10.1210/jc.2008-1385
M3 - Journal article
C2 - 19066303
VL - 94
SP - 965
EP - 972
JO - Journal of Clinical Endocrinology and Metabolism
JF - Journal of Clinical Endocrinology and Metabolism
SN - 0021-972X
IS - 3
ER -