Glomerular structural and functional changes in a high-fat diet mouse model of early-stage Type 2 diabetes

Diabetologia
P WeiS C Sansom

Abstract

Type 2 diabetes often results in diabetic nephropathy, which is preceded by an elevated glomerular filtration rate (GFR). This study was designed to develop a mouse model of Type 2 diabetes and to elucidate the glomerular events in the early stages of diabetic nephropathy. Four-week-old mice were fed a normal or high-fat (42% of total calories from fat) diet, and body weight, blood glucose, insulin, leptin, lipids and GFR were monitored from 9 to 21 weeks or longer after the feeding programme. Mesangial cell dedifferentiation was accessed by alpha-smooth muscle actin staining. Glomerular hypertrophy was determined using image analysis with haematoxylin-eosin staining. Matrix deposition was determined by type IV collagen staining. After 9 weeks, mice fed a high-fat diet weighed more than mice fed a normal diet (30.5+/-1.2 vs 22.3+/-0.5 g, p<0.05), and mice fed a high-fat diet were hyperinsulinaemic (283.9+/-69.7 vs 102.9+/-36.4 pmol/l, p<0.05), hyperglycaemic (8.0+/-0.6 vs 6.5+/-0.2 mmol/l, p<0.05) and their leptin levels were increased six-fold (1.48+/-0.45 vs 0.25+/-0.03 ng/ml, p<0.05). After 13 weeks, mice fed a high-fat diet showed hyperfiltration (GFR; 440+/-60 vs 210+/-10 microl/min, p<0.05). During the early stages of dia...Continue Reading

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