Insulin and GH signaling in human skeletal muscle in vivo following exogenous GH exposure: impact of an oral glucose load |
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Authors: | Krusenstjerna-Hafstrøm Thomas Madsen Michael Vendelbo Mikkel H Pedersen Steen B Christiansen Jens S Møller Niels Jessen Niels Jørgensen Jens O L |
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Institution: | 1Department of Internal Medicine and Endocrinology (MEA) and Medical Research Laboratories, Aarhus University Hospital, Aarhus, Denmark;2Department of Clinical Pharmacology, Aarhus University Hospital, Aarhus, Denmark;University of Padova, Medical School, Italy |
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Abstract: | IntroductionGH induces acute insulin resistance in skeletal muscle in vivo, which in
rodent models has been attributed to crosstalk between GH and insulin
signaling pathways. Our objective was to characterize time course changes in
signaling pathways for GH and insulin in human skeletal muscle in vivo
following GH exposure in the presence and absence of an oral glucose
load.MethodsEight young men were studied in a single-blinded randomized crossover design
on 3 occasions: 1) after an intravenous GH bolus 2) after an intravenous GH
bolus plus an oral glucose load (OGTT), and 3) after intravenous saline plus
OGTT. Muscle biopsies were taken at t?=?0, 30, 60, and
120. Blood was sampled at frequent intervals for assessment of GH, insulin,
glucose, and free fatty acids (FFA).ResultsGH increased AUCglucose after an OGTT (p<0.05) without
significant changes in serum insulin levels. GH induced phosphorylation of
STAT5 independently of the OGTT. Conversely, the OGTT induced acute
phosphorylation of the insulin signaling proteins Akt (ser473 and
thr308), and AS160.The combination of OGTT and GH suppressed
Akt activation, whereas the downstream expression of AS160 was amplified by
GH.We Concluded the Following1) A physiological GH bolus activates STAT5 signaling pathways in skeletal
muscle irrespective of ambient glucose and insulin levels 2) Insulin
resistance induced by GH occurs without a distinct suppression of insulin
signaling proteins 3) The accentuation of the glucose-stimulated activation
of AS 160 by GH does however indicate a potential crosstalk between insulin
and GH.Trial RegistrationClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00477997","term_id":"NCT00477997"}}NCT00477997 |
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