Gastric inhibitory polypeptide (GIP) suppresses circulating ghrelin in humans: plasma metabolome based correlation network analysis for support of hormone-to- hormone interactions
Natalia Rudovich1,2, Victoria J Nikiforova3, Baerbel Otto4, Olga Pivovarova1,2, Özlem Gögebakan1,2, Martin O Weickert1,2, Michael A Nauck5 & Andreas F H Pfeiffer1,2
Aims: We investigate the influence of GIP on ghrelin secretion in normal glucose tolerant individuals with the use of the firstly applied correlation network analysis on human plasma metabolome data.
Methods: To address this issue, we employed a GIP-infusion test and euglycemic- and hyperglycemic glucose clamp experiments combined with infusion of GIP or placebo in a cross-over manner in non diabetic obese male subjects (n=14). Moreover, we firstly applied correlation network analysis on GC-TOF/MS plasma metabolite profiles of the accomplished experiments for testing of the supposed GIP to ghrelin interactions.
Results: Our major finding is that GIP significantly suppressed ghrelin secretion under hyperglycemic hyperinsulinemic conditions (34.3% versus baseline, P<0.05), supported by the strongest involvement of ghrelin into the network of molecular information exchange particularly at this condition. Only a moderate effect of GIP on ghrelin secretion was observed during euglycemic, hyperinsulinemic clamps (12.6%, P<0.05), with very weak ghrelin integration into the molecular information exchange.
Conclusions: The suppression of ghrelin secretion requires hyperglycaemic conditions, similar to the insulinotropic action of GIP. These findings indicate an indirect effect of GIP via ghrelin on the suppression of hunger sensation and appetite. Moreover we considered necessary to apply systems analysis to the search of informational signals for ghrelin regulation and involvement of different metabolites in this process.