Rosiglitazone improves intestinal lipoprotein overproduction in the fat-fed Syrian Golden hamster, an animal model of nutritionally-induced insulin resistance.
We have recently shown that the fructose-fed Syrian Golden hamster, a non-diabetic animal model of nutritionally-induced insulin resistance and hyperlipidemia, is characterized by intestinal lipoprotein overproduction. In order to determine whether intestinal lipoprotein overproduction is specific to fructose feeding or applies generally to other models of insulin resistance, we studied intestinal lipoprotein production and the response to insulin sensitization in the high fat-fed Syrian Golden hamster. Syrian Golden Hamsters were fed either (1). chow (CHOW), (2). 60% fat (FAT) or (3). 60% fat with rosiglitazone, 20 micromol/kg per day (FAT + RSG) for 5 weeks. Euglycemic hyperinsulinemic clamp studies confirmed that FAT is a good model of insulin resistance and rosiglitazone treatment resulted in a significant improvement in insulin sensitivity. In addition, there was a significant approx. two- to four-fold increase in intestinal apoB48 particle production in FAT. Rosiglitazone treatment resulted in partial normalization of apoB48-containing intestinal lipoprotein secretion. In summary: (1). the fat-fed Syrian Golden Hamster is a good model of nutritionally-induced insulin resistance, (2). intestinal overproduction of lipoproteins appear to contribute to the hypertriglyceridemia of insulin resistance in this animal model and (3). insulin sensitization with rosiglitazone ameliorates intestinal apoB48 particle overproduction in the fat-fed Syrian Golden Hamster. These data further support the link between insulin resistance and intestinal lipoprotein overproduction.
Leung
Nathalie
N
Department of Medicine, University of Toronto, Toronto, Ont, Canada.
Naples
Mark
M
Uffelman
Kristine
K
Szeto
Linda
L
Adeli
Khosrow
K
Lewis
Gary F
GF
D000704:Analysis of Variance; D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D006224:Cricetinae; D004041:Dietary Fats / Q000494:pharmacology; D004195:Disease Models, Animal; D015309:Glucose Clamp Technique; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007333:Insulin Resistance / Q000502:physiology*; D007408:Intestinal Absorption / Q000187:drug effects; D007413:Intestinal Mucosa / Q000378:metabolism*; D008074:Lipoproteins / Q000096:biosynthesis* / Q000378:metabolism; D008297:Male; D008647:Mesocricetus; D011336:Probability; D011897:Random Allocation; D000077154:Rosiglitazone; D012680:Sensitivity and Specificity; D045162:Thiazolidinediones / Q000494:pharmacology*
D001786:Blood Glucose; D004041:Dietary Fats; D007004:Hypoglycemic Agents; D008074:Lipoproteins; D045162:Thiazolidinediones; D000077154:Rosiglitazone