GLP-1 and GLP-2 as Ying and Yang of Intestinal Lipoprotein Production: Evidence for predominance of GLP-2-stimulated postprandial lipemia in normal and insulin Resistant States

HEIN GJ; BAKER C; HSIEH J; FARR S; ADELI K

DIABETES

AMER DIABETES ASSOC

Lugar: Indianapolis; Año: 2013 vol. 62 p. 373 - 381

0012-1797

The glucagon-like peptides (GLP-1 and -2) are processed from the proglucagon polypeptide andsecreted in equimolar amounts, but have opposite effects on chylomicron (CM) production, withGLP-1 significantly reducing while GLP-2 increasing postprandial chylomicronemia. In thecurrent study, we evaluated the apparent paradoxical roles of GLP-1 and GLP-2 underphysiological conditions in the Syrian golden hamster, a model with close similarity to humansin terms of lipoprotein metabolism. A short (30 min) intravenous infusion of GLP-2 resulted in amarked increase in postprandial apoB48 and TG levels in the TG-rich lipoprotein (TRL) fractionwhile GLP-1 infusion decreased lipid absorption and TRL-TG and apoB48. GLP-1 and GLP-2co-infusion resulted in net increased lipid absorption and TRL-TG and apoB48. However,prolonged (120 min) co-infusion of GLP-1 and GLP-2 decreased postprandial lipemia. Blockingdipeptidyl peptidase-4 activity resulted in decreased postprandial lipemia. Interestingly, fructosefedinsulin resistant hamsters showed a more pronounced response and possible hypersensitivityto GLP-2 or reduced sensitivity to GLP-1. In conclusion, under normal physiological conditions,the actions of GLP-2 predominate, however when GLP-1 activity is sustained, the hypolipidemicaction of GLP-1 predominates. Pharmacological inhibition of GLP-1 degradation tips the balancetowards an inhibitory effect on intestinal production of atherogenic CM particles.