Effects of GLP-1 and GLP-2 co-administration on regulation of intestinal lipid metabolism and chylomicron production in Syrian golden hamsters

HEIN, GUSTAVO J.; BAKER, CHRISTOPHER L.; HSIEH, JOANNE; ADELI, KHOSROW

San Diego, California, Estados Unidos

Congreso; 71st scientific sessions - American Diabetes Association; 2011

American Diabetes Association

Postprandial hypertriglyceridemia and hyper-chylomicronemia are mayor complications of insulin resistant states. Glucagons-like peptides (GLP-1) and GLP-2 are derived from post-translational processing of the proglucagon polypeptide and are co-secreted in equimolar amounts. There is evidence indicating that while GLP-1 exerts an acute suppressive effect, GLP-2 triggers marked stimulation of fatty acid absorption and chylomicron (CM) production. The interplay between these two peptides in the regulation of intestinal CM is intriguing, but their relative contribution to the CM pathway is currently unknown. To determine the contribution of GLP-1 and GLP-2 to regulation of intestinal lipid metabolism and CM production, we analyzed the effects on the in vivo production of ApoB48, triglyceride-rich lipoprotein (TRL)-triglycerides and TRLcholesterollevels and fatty acid absorption after an intravenous (IV) infusion of physiological levels of GLP-1, GLP-2 or both in Syrian golden hamsters. GLP-1 decreased intestinal ApoB48 production, TRL-triglycerides and TRL-cholesterol (p<0.05) and decreased fatty acid absorption (p<0.05), while GLP-2 increased these parameters (p<0.05). On the other hand, these parameters were significant increased (p<0.05) with simultaneous infusion of GLP-1 and GLP-2. Peripheral co-administration of both peptides reveals a predominant role for GLP-2 promote CM production (late phase: 60-120 minutes) when co-infused with GLP-1 at equimolar concentrations. This would suggest that physiologically, GLP-1 effect seems to be responsible for inhibiting CM production in early stages, while GLP-2 increases CM production over a prolonged period.