Intestinal lipoprotein overproduction in insulin-resistant states.
OBJECTIVE
Excessive postprandial lipemia is highly prevalent in obese and insulin-resistant/type 2 diabetic individuals and substantially increases the risk of atherosclerosis and cardiovascular disease. This article will review our current understanding of the link between insulin resistance and intestinal lipoprotein overproduction and highlight some of the key recent findings in the field.


RESULTS
Emerging evidence from several animal models of insulin resistance as well as insulin-resistant humans clearly supports the link between insulin resistance and aberrant intestinal lipoprotein metabolism. In insulin-resistant states, elevated free fatty acid flux into the intestine, downregulation of intestinal insulin signaling and upregulation of microsomal triglyceride transfer protein all appear to stimulate intestinal lipoprotein production. Gut peptides, GLP-1 and GLP-2, may be important regulators of intestinal lipid absorption and lipoprotein production.


CONCLUSIONS
Available evidence in humans and animal models strongly favors the concept that the small intestine is not merely an absorptive organ but rather plays an active role in regulating the rate of production of triglyceride-rich lipoproteins. Metabolic signals in insulin resistance and type 2 diabetes and in some cases an aberrant intestinal response to these factors all contribute to the enhanced formation and secretion of triglyceride-rich lipoproteins.
Adeli
Khosrow
K
Molecular Structure and Function, Research Institute, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada. khosrow.adeli@sickkids.ca
Lewis
Gary F
GF
D000818:Animals; D005230:Fatty Acids, Nonesterified / Q000097:blood; D052216:Glucagon-Like Peptide 1 / Q000502:physiology; D053767:Glucagon-Like Peptide 2 / Q000502:physiology; D006801:Humans; D007333:Insulin Resistance; D007413:Intestinal Mucosa / Q000378:metabolism*; D008074:Lipoproteins / Q000096:biosynthesis*; D008099:Liver / Q000378:metabolism; D023421:Models, Animal
D005230:Fatty Acids, Nonesterified; D053767:Glucagon-Like Peptide 2; D008074:Lipoproteins; D052216:Glucagon-Like Peptide 1