Insulin and GH signaling in human skeletal muscle in vivo following exogenous GH exposure: impact of an oral glucose load

Introduction

GH induces acute insulin resistance in skeletal muscle in vivo, which inrodent models has been attributed to crosstalk between GH and insulinsignaling pathways. Our objective was to characterize time course changes insignaling pathways for GH and insulin in human skeletal muscle in vivofollowing GH exposure in the presence and absence of an oral glucoseload.

Methods

Eight young men were studied in a single-blinded randomized crossover designon 3 occasions: 1) after an intravenous GH bolus 2) after an intravenous GHbolus plus an oral glucose load (OGTT), and 3) after intravenous saline plusOGTT. Muscle biopsies were taken at t = 0, 30, 60, and120. Blood was sampled at frequent intervals for assessment of GH, insulin,glucose, and free fatty acids (FFA).

Results

GH increased AUC_glucose after an OGTT (p<0.05) withoutsignificant changes in serum insulin levels. GH induced phosphorylation ofSTAT5 independently of the OGTT. Conversely, the OGTT induced acutephosphorylation of the insulin signaling proteins Akt (ser⁴⁷³ andthr³⁰⁸), and AS160.The combination of OGTT and GH suppressedAkt activation, whereas the downstream expression of AS160 was amplified byGH.

We Concluded the Following

1) A physiological GH bolus activates STAT5 signaling pathways in skeletalmuscle irrespective of ambient glucose and insulin levels 2) Insulinresistance induced by GH occurs without a distinct suppression of insulinsignaling proteins 3) The accentuation of the glucose-stimulated activationof AS 160 by GH does however indicate a potential crosstalk between insulinand GH.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00477997","term_id":"NCT00477997"}}NCT00477997