title: Type 2 diabetes mellitus in a non-obese mouse model induced by Meg1/Grb10 overexpression.
abstract: We assessed the possibility of C57BL/6-Tg (Meg1/Grb10)isn(Meg1 Tg) mice as a non-obese type 2 diabetes (2DM) animal model. Meg1 Tg mice were born normal, but their weight did not increase as much as normal after weaning and showed about 85% of normal size at 20 weeks of age. Body mass index of Meg1 Tg mice was also smaller than that of control mice. The glucose tolerance test and insulin tolerance test showed that Meg1 Tg mice had reduced ability to normalize the blood glucose level. Blood urea nitrogen (BUN) in Meg1 Tg mice (19.6 +/- 1.2 mg/dl) was significantly lower than in controls (22.0 +/- 0.8 mg/dl), while plasma triglyceride, insulin, adiponectin, and resistin levels were significantly higher (202.0 +/- 23.4 mg/dl vs 146.3 +/- 23.4 mg/dl, 152.4 +/- 16.3 pg/ml vs 88.1 +/- 16.9 pg/ml, 74.4 +/- 10.9 microg/ml vs 48.3 +/- 7.0 microg/ml, and 4.0 +/- 0.2 ng/ml vs 3.6 +/- 0.2 ng/ml, respectively). Body, visceral fat weight and liver weights were significantly lower (19.6 +/- 0.4 g vs 24.3 +/- 0.3 g, 376.7 +/- 29.6 mg to 507.5 +/- 23.0 mg, and 906.0 +/- 41.8 mg to 1,001.0 +/- 15.1 mg, respectively). Thus, hyperinsulinemia observed in Meg1 Tg mice indicates that their insulin signaling pathway is somehow inhibited. With high fat diet, the diabetes onset rate of Meg1 Tg mice increased up to 60%. These results suggest that Meg1 Tg mice resemble human 2DM.
authors.affiliation: Department of Veterinary Science, National Institute of Infectious Diseases, Shinjuku-ku, Tokyo, Japan.
authors.forename: Yoshie
authors.initials: Y
authors.lastname: Yamamoto
authors.forename: Fumitoshi
authors.initials: F
authors.lastname: Ishino
authors.forename: Tomoko
authors.initials: T
authors.lastname: Kaneko-Ishino
authors.forename: Hirosuke
authors.initials: H
authors.lastname: Shiura
authors.forename: Kozue
authors.initials: K
authors.lastname: Uchio-Yamada
authors.forename: Junichiro
authors.initials: J
authors.lastname: Matsuda
authors.forename: Osamu
authors.initials: O
authors.lastname: Suzuki
authors.forename: Katsunori
authors.initials: K
authors.lastname: Sato
mesh_terms: D052242:Adiponectin / Q000097:blood; D000818:Animals; D001806:Blood Urea Nitrogen; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000662:veterinary*; D004041:Dietary Fats; D004195:Disease Models, Animal; D005951:Glucose Tolerance Test; D007328:Insulin / Q000097:blood / Q000494:pharmacology; D008049:Lipase / Q000097:blood; D051379:Mice; D008822:Mice, Transgenic; D052243:Resistin / Q000097:blood; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D052242:Adiponectin; D004041:Dietary Fats; D007328:Insulin; D052243:Resistin; D008049:Lipase