Characterization of beta-cell mass and insulin resistance in diet-induced obese and diet-resistant rats.
The selectively bred diet-induced obese (DIO) and diet-resistant (DR) rats represent a polygenetic animal model mimicking most clinical variables characterizing the human metabolic syndrome. When fed a high-energy (HE) diet DIO rats develop visceral obesity, dyslipidemia, hyperinsulinemia, and insulin resistance but never frank diabetes. To improve our understanding of the underlying cause for the deteriorating glucose and insulin parameters, we have investigated possible adaptive responses in DIO and DR rats at the level of the insulin-producing beta-cells. At the time of weaning, DR rats were found to have a higher body weight and beta-cell mass compared to DIO rats, and elevated insulin and glucose responses to an oral glucose load. However, at 2.5 months of age, and for the remaining study period, the effect of genotype became evident: the chow-fed DIO rats steadily increased their body weight and beta-cell mass, as well as insulin and glucose levels compared to the DR rats. HE feeding affected both DIO and DR rats leading to an increased body weight and an increased beta-cell mass. Interestingly, although the beta-cell mass in DR rats and chow-fed DIO rats appeared to constantly increase with age, the beta-cell mass in the HE-fed DIO rats did not continue to do so. This might constitute part of an explanation for their reduced glucose tolerance. Collectively, the data support the use of HE-fed DIO rats as a model of human obesity and insulin resistance, and accentuate its relevance for studies examining the benefit of pharmaceutical compounds targeting this disease complex.
Paulsen
Sarah J
SJ
Rheoscience A/S, Rødovre, Denmark.
Jelsing
Jacob
J
Madsen
Andreas N
AN
Hansen
Gitte
G
Lykkegaard
Kirsten
K
Larsen
Leif K
LK
Larsen
Philip J
PJ
Levin
Barry E
BE
Vrang
Niels
N
D000367:Age Factors; D000375:Aging; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight; D003920:Diabetes Mellitus / Q000235:genetics / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology*; D004032:Diet; D004195:Disease Models, Animal; D020022:Genetic Predisposition to Disease; D005951:Glucose Tolerance Test; D006706:Homeostasis; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance / Q000235:genetics; D050417:Insulin-Secreting Cells / Q000378:metabolism / Q000473:pathology*; D008297:Male; D009765:Obesity / Q000235:genetics / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology*; D010641:Phenotype; D011236:Prediabetic State / Q000235:genetics / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology*; D051381:Rats
D001786:Blood Glucose; D007328:Insulin