title: Long-term renal changes in the liver-specific glucokinase knockout mouse: implications for renal disease in maturity-onset diabetes of the young 2.
abstract: To investigate the functional and structural renal changes in a long-term liver-specific glucokinase (gck) knockout mouse, a model was developed of maturity-onset diabetes of the young (MODY2). Hemizygous gck knockout mice, gck(w/-) groups, were compared at 6, 10, and 14 months with their age-matched normal littermates, gck(w/w) groups. To examine changes, we compared body weight, fasting blood glucose, serum insulin, and creatinine levels, as well as 24-h urine samples that were collected for urine volume and protein analysis between the 2 groups. Renal tissues were collected and stained with hemotoxylin-eosin and periodic-acid Schiff for light microscopic observation. The expression of renal transforming growth factor β1 (TGF-β1) was determined by Western blot. Our results show that fasting blood glucose levels were significantly higher in gck(w/-) mice compared with gck(w/w) mice (P < 0.01) for all age groups. Compared with age-matched gck(w/w) mice, 10-month old gck(w/-) mice have significantly elevated body weights (P < 0.01) and protein contents (P < 0.001). A gradual increase in mesangial matrix and a thickening of the glomerular basement membrane was observed in gck(w/-) mice at 10 and 14 months. The levels of renal TGF-β1 expression are increasing in both gck(w/-) and gck(w/w) mice. Our results indicate that renal changes occur in the liver-specific gck knockout mouse model of MODY2 and suggest that TGF-β1 may play a key role in pathogenesis of these renal changes.
authors.affiliation: School of Basic Medical Sciences, Department of Pharmacology, Peking University, Beijing, PR China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Gu
authors.forename: Yiqing
authors.initials: Y
authors.lastname: Mao
authors.forename: Hui
authors.initials: H
authors.lastname: Li
authors.forename: Shuyong
authors.initials: S
authors.lastname: Zhao
authors.forename: Yang
authors.initials: Y
authors.lastname: Yang
authors.forename: Hui
authors.initials: H
authors.lastname: Gao
authors.forename: Jianqiang
authors.initials: J
authors.lastname: Yu
authors.forename: Xuemei
authors.initials: X
authors.lastname: Zhang
authors.forename: David M
authors.initials: DM
authors.lastname: Irwin
authors.forename: Gang
authors.initials: G
authors.lastname: Niu
authors.forename: Huanran
authors.initials: H
authors.lastname: Tan
mesh_terms: D000367:Age Factors; D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000201:enzymology* / Q000209:etiology / Q000235:genetics; D003928:Diabetic Nephropathies / Q000201:enzymology* / Q000209:etiology / Q000235:genetics / Q000473:pathology; D004195:Disease Models, Animal; D055786:Gene Knockout Techniques; D005920:Glomerular Mesangium / Q000473:pathology; D005941:Glucokinase / Q000172:deficiency* / Q000235:genetics; D006801:Humans; D007668:Kidney / Q000378:metabolism / Q000473:pathology; D008099:Liver / Q000201:enzymology*; D051379:Mice; D018345:Mice, Knockout; D053773:Transforming Growth Factor beta1 / Q000378:metabolism
chemical_list: D053773:Transforming Growth Factor beta1; D005941:Glucokinase