Gut Peptides Are Novel Regulators of Intestinal Lipoprotein Secretion: Experimental and Pharmacological Manipulation of Lipoprotein Metabolism

Abstract

Individuals with metabolic syndrome and frank type 2 diabetes are at increased risk of atherosclerotic cardiovascular disease, partially due to the presence of lipid and lipoprotein abnormalities. In these conditions, the liver and intestine overproduce lipoprotein particles, exacerbating the hyperlipidemia of fasting and postprandial states. Incretin-based, antidiabetes therapies (i.e., glucagon-like peptide [GLP]-1 receptor agonists and dipeptidyl peptidase-4 inhibitors) have proven efficacy for the treatment of hyperglycemia. Evidence is accumulating that these agents also improve fasting and postprandial lipemia, the latter more significantly than the former. In contrast, the gut-derived peptide GLP-2, cosecreted from intestinal L cells with GLP-1, has recently been demonstrated to enhance intestinal lipoprotein release. Understanding the roles of these emerging regulators of intestinal lipoprotein secretion may offer new insights into the regulation of intestinal lipoprotein assembly and secretion and provide new opportunities for devising novel strategies to attenuate hyperlipidemia, with the potential for cardiovascular disease reduction.

The Canadian laboratory initiative on pediatric reference intervals: A CALIPER white paper

“…Pediatric reference intervals for markers of metabolic disease, steroid hormones, and vitamins a and E (HPLC, UPLC, LC-MS/MS). [53,54]). Similar to using the oral glucose tolerance test to determine impaired glucose tolerance and increased risk of type 2 diabetes, the "oral fat tolerance test" may be a helpful tool to determine impaired lipid tolerance and increased risk for cardiovascular events.…”

Intravenous Glucose Acutely Stimulates Intestinal Lipoprotein Secretion in Healthy Humans

“…In this study, TRL-apoB48 stable isotopic enrichments were similar between treatments, suggesting that release of preformed chylomicron by intravenous glucose, if any, was not greater than by saline during the kinetic study. Gut hormones GLP-1 and GLP-2 are known to affect intestinal lipoprotein secretion 22 and GLP-2 rapidly promotes the release of preformed chylomicron. 21 Because GLP-2 cosecretes with GLP-1 on a 1:1 molar ratio 23 and GLP-1 secretion is stimulated by luminal but not vascular glucose, 24 it is unlikely that GLP-1 or GLP-2 played a significant role in this study.…”

Pharmacological Targeting of the Atherogenic Dyslipidemia Complex: The Next Frontier in CVD Prevention Beyond Lowering LDL Cholesterol

“…Among those, the incretin-based antidiabetic drugs exenatide (a glucagon-like peptide-1 receptor agonist) and sitagliptin (a dipeptidyl peptidase-4 inhibitor) suppress intestinal lipoprotein production in the short term in humans (119,120). Incretin-based antidiabetic drugs also attenuated postprandial TG excursion in clinical trials (reviewed in Xiao et al [121]). Several recent CVD outcomes trials (122)(123)(124) have demonstrated the noninferiority of several such agents in T2D patients with established CVD or with increased CVD risks, and more trials with other agents are underway.…”