glucagon-like-peptide-2 and Hyperlipidemias

Glucose and lipids stimulate the gut-hormones glucagon-like peptide (GLP)-1, GLP-2 and glucose-dependent insulinotropic polypeptide (GIP) but the effect of these on human postprandial lipid metabolism is not fully clarified.. To explore the responses of GLP-1, GLP-2 and GIP after a fat-rich meal compared to the same responses after an oral glucose tolerance test (OGTT) and to investigate possible relationships between incretin response and triglyceride-rich lipoprotein (TRL) response to a fat-rich meal.. Glucose, insulin, GLP-1, GLP-2 and GIP were measured after an OGTT and after a fat-rich meal in 65 healthy obese (BMI 26.5-40.2 kg/m(2)) male subjects. Triglycerides (TG), apoB48 and apoB100 in TG-rich lipoproteins (chylomicrons, VLDL1 and VLDL2) were measured after the fat-rich meal.. Postprandial responses (area under the curve, AUC) for glucose, insulin, GLP-1, GLP-2, GIP in plasma, and TG, apoB48 and apoB100 in plasma and TG-rich lipoproteins.. The GLP-1, GLP-2 and GIP responses after the fat-rich meal and after the OGTT correlated strongly (r = 0.73, p<0.0001; r = 0.46, p<0.001 and r = 0.69, p<0.001, respectively). Glucose and insulin AUCs were lower, but the AUCs for GLP-1, GLP-2 and GIP were significantly higher after the fat-rich meal than after the OGTT. The peak value for all hormones appeared at 120 minutes after the fat-rich meal, compared to 30 minutes after the OGTT. After the fat-rich meal, the AUCs for GLP-1, GLP-2 and GIP correlated significantly with plasma TG- and apoB48 AUCs but the contribution was very modest.. In obese males, GLP-1, GLP-2 and GIP responses to a fat-rich meal are greater than following an OGTT. However, the most important explanatory variable for postprandial TG excursion was fasting triglycerides. The contribution of endogenous GLP-1, GLP-2 and GIP to explaining the variance in postprandial TG excursion was minor.

Topics: Adult; Aged; Apolipoprotein B-100; Apolipoprotein B-48; Area Under Curve; Blood Glucose; Chylomicrons; Dietary Fats; Gastric Inhibitory Polypeptide; Glucagon-Like Peptide 1; Glucagon-Like Peptide 2; Glucose Tolerance Test; Humans; Hyperlipidemias; Incretins; Lipid Metabolism; Male; Meals; Middle Aged; Obesity; Postprandial Period; Triglycerides

The glucagon-like peptides (GLP-1 and GLP-2) are processed from the proglucagon polypeptide and secreted in equimolar amounts but have opposite effects on chylomicron (CM) production, with GLP-1 significantly reducing and GLP-2 increasing postprandial chylomicronemia. In the current study, we evaluated the apparent paradoxical roles of GLP-1 and GLP-2 under physiological conditions in the Syrian golden hamster, a model with close similarity to humans in terms of lipoprotein metabolism. A short (30-min) intravenous infusion of GLP-2 resulted in a marked increase in postprandial apolipoprotein B48 (apoB48) and triglyceride (TG) levels in the TG-rich lipoprotein (TRL) fraction, whereas GLP-1 infusion decreased lipid absorption and levels of TRL-TG and apoB48. GLP-1 and GLP-2 coinfusion resulted in net increased lipid absorption and an increase in TRL-TG and apoB48. However, prolonged (120-min) coinfusion of GLP-1 and GLP-2 decreased postprandial lipemia. Blocking dipeptidyl peptidase-4 activity resulted in decreased postprandial lipemia. Interestingly, fructose-fed, insulin-resistant hamsters showed a more pronounced response, including possible hypersensitivity to 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 hypolipidemic action of GLP-1 predominates. Pharmacological inhibition of GLP-1 degradation tips the balance toward an inhibitory effect on intestinal production of atherogenic CM particles.

Topics: Animals; Apolipoprotein B-48; Chylomicrons; Cricetinae; Dipeptidyl-Peptidase IV Inhibitors; Fructose; Glucagon-Like Peptide 1; Glucagon-Like Peptide 2; Hyperlipidemias; Insulin Resistance; Intestinal Absorption; Intestines; Lipid Metabolism; Lipoproteins; Male; Mesocricetus; Postprandial Period; Triglycerides

Topics: Animals; Glucagon-Like Peptide 1; Glucagon-Like Peptide 2; Hyperlipidemias; Insulin Resistance; Intestines; Lipoproteins; Male; Postprandial Period