Linked Life Data

11427207

Source:http://linkedlifedata.com/resource/pubmed/id/11427207

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2001-6-27
pubmed:abstractText
The liver plays a central role in lipoprotein metabolism and cholesterol homeostasis. As the physiopathology of lipid disorders in non-insulin-dependent diabetes mellitus (NIDDM) is multifactorial and still imperfectly known, we evaluated its onset on plasma lipid transport and hepatic cholesterol metabolism in Psammomys obesus. This sand rat lapses into hyperinsulinemia and hyperglycemia when transferred from its native food to laboratory rodent diets. Marked hypertriglyceridemia and hypercholesterolemia developed in hyperinsulinemic (Group B) and hyperglycemic/ hyperinsulinemic (Group C), compared with normal P. obesus (Group A). Group B showed significantly (P<0.05) higher plasma VLDL-cholesterol (41.9%) and LDL-cholesterol (47.3%) concentrations, whereas Group C was characterized by an even more marked increase in VLDL-cholesterol (176%, P<0.001) compared with Group A. Lipoprotein composition was also altered, displaying impaired lipid and apolipoprotein moiety distribution in IDL, LDL, HDL(2) and HDL(3) lipoprotein fractions of Groups B and C. The activity of hepatic 3-hydroxy-3-methylglutaryl coenzyme A reductase, the rate-limiting enzyme in cholesterol biosynthesis, was consistently lower in Group B (P<63.4%, P<0.001) and C (43.9%, P<0.005). In contrast, the direct measurement of microsomal acyl-CoA:cholesterol acyltransferase (ACAT), controlling the acylation of cholesterol, showed an increase averaging 53% in Group B (P<0.01) and 61% in Group C (P<0.005). Similarly, elevated activity (171.1%, P<0.05 and 291.4%, P<0.001, respectively) was related to cholesterol 7alpha-hydroxylase, the rate-limiting enzyme in bile acid biosynthesis. These alterations were accompanied with abundant deposition of triglycerides and cholesterol in the liver. Changes in circulating lipids and liver parameters were related to glucose and insulin levels, indicating the implication of insulin resistance and diabetes. Therefore, our findings demonstrate various disturbances in plasma lipid profile and lipoprotein composition, as well as in liver cholesterol metabolism during the sequential development of insulin resistance and diabetes in P. obesus rats. Furthermore, the current data point to an undoubtedly important role of the liver in the pathogenesis of metabolic disorders in the progression of nutritionally-induced insulin resistance and diabetes in P. obesus. Finally, current research shows that more marked plasma and hepatic lipid perturbations occur in insulin resistance than in diabetes, which may culminate in the development of atherosclerosis.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0021-9150
pubmed:author
pubmed:issnType
Print
pubmed:volume
157
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
85-96
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
2001
pubmed:articleTitle
Circulating lipoproteins and hepatic sterol metabolism in Psammomys obesus prone to obesity, hyperglycemia and hyperinsulinemia.
pubmed:affiliation
Centre de Recherche, Hôpital Sainte-Justine, Université de Montréal, 3175 Côte Ste-Catherine Road, Montreal, Quebec, Canada, H3T IC5.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't