Time course of hepatic gluconeogenesis during hindlimb suspension unloading

摘要: The goal of this work was to determine the time-dependent changes in fractional hepatic gluconeogenesis(GNG)duringconditionsofhindlimbsuspensionunloading(HSU),a‘groundbased’ method for inducing muscular atrophy simulate space flight. We hypothesized that GNG would increase HSU conditions as a result metabolic shifts liver and skeletal muscle. A significant progressive observed soleus (30, 47 55%) gastrocnemius muscles (0, 15 17%) after 3, 7 14 days HSU, respectively. Fractional determined following incorporation deuterium from deuterated water ( 2 H2O) into C–H bonds newly synthesized glucose an 8 h fast. Enrichment plasma with H measured using classic Landau et al. (the ‘hexamethylenetetramine (HMT) method’), based on specific labelling carbons, novel Chacko (‘average assumption equal enrichment all carbons (except C2). After 3 significantlyelevatedintheHSUgroup,asdeterminedbyeithermethod(∼13%,P <0.05).After gluconeogenesis not significantly different. Both analytical methods yieldedsimilartime-dependenttrendsingluconeogenicrates,butGNGvaluesdeterminedusing average were consistently lower (∼30%) than those found by HMT method. To compare validate against further, we starved animals 13 allow contribute 100% endogenous production. yielded GNG, while ∼70%. As both methodsusedthesamevaluesofprecursorenrichment,wepostulatedthattheunderestimation gluconeogenic rate differences measurements product glucose). This could be explained factors: (i) loss via exchange between acetate glucose; (ii) interference caused fragment m/z 169, representing multiple isobaric species; (iii)interference other sugars at 169. In conclusion, gluconeogenesis, irrespective used.