Document Detail


The intestine as a regulator of cholesterol homeostasis in diabetes.
MedLine Citation:
PMID:  18693145     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The chylomicron influences very low-density lipoprotein (VLDL) and low-density lipoprotein (LDL) composition but itself is atherogenic. Thus abnormalities of chylomicron production are of interest particularly in conditions such as diabetes which confer major cardiovascular risk. Intestinal function is abnormal in diabetes and is a major cause of the dyslipidaemia found in this condition. Studies have suggested that cholesterol absorption is decreased in diabetes and cholesterol synthesis increased. Molecular mechanisms involved in insulin resistance in the intestine and its effect on cholesterol homeostasis in diabetes are described. Abnormalities in triglyceride synthesis and alterations genes regulating cholesterol absorption and intestinal synthesis are discussed. In particular, increase in apolipoprotein B48 synthesis has been demonstrated in animal models of diabetes and insulin resistance. Intestinal mRNA expression of Niemann Pick C1-like 1, protein is increased in both experimental and human diabetes suggesting that an increase in cholesterol transportation does occur. mRNA expression of the ATP binding cassette proteins (ABC) G5 and G8, two proteins working in tandem to excrete cholesterol have been shown to be decreased suggesting increased delivery of cholesterol for absorption. Expression of microsomal triglyceride transfer protein, which assembles the chylomicron particle, is increased in diabetes leading to increase in both number and cholesterol content. In conclusion, diabetes is associated with considerable dysfunction of the intestine leading to abnormal chylomicron composition which may play a major part in the premature development of atherosclerosis.
Authors:
Gerald H Tomkin
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Publication Detail:
Type:  Journal Article; Review     Date:  2008-08-06
Journal Detail:
Title:  Atherosclerosis. Supplements     Volume:  9     ISSN:  1567-5688     ISO Abbreviation:  Atheroscler Suppl     Publication Date:  2008 Sep 
Date Detail:
Created Date:  2008-09-08     Completed Date:  2009-01-06     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  100973461     Medline TA:  Atheroscler Suppl     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  27-32     Citation Subset:  IM    
Affiliation:
Diabetes Institute of Ireland, Beacon Clinic Dublin, and Blackrock Clinic Dublin, Department of Medicine, Trinity College, Dublin, Ireland. Gerald.tomkin@tcd.ie
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MeSH Terms
Descriptor/Qualifier:
Animals
Cholesterol / metabolism*
Chylomicrons / metabolism
Diabetes Mellitus / metabolism*
Humans
Intestinal Absorption / physiology
Intestines / metabolism*
Chemical
Reg. No./Substance:
0/Chylomicrons; 57-88-5/Cholesterol

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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