title: Reconsideration of insulin signals induced by improved laboratory animal diets, Japanese and American diets, in IRS-2 deficient mice.
abstract: Current Japanese and American diets and Japanese diet immediately after the War were converted to laboratory animal diets. As a result, current laboratory animal diet (CA-1, CLEA) unexpectedly resembled the diet of Japanese after the War. This is considered to result in an under-evaluation of diabetes research using laboratory animals at present. Therefore, changes in insulin signals caused by current Japanese and American diets were examined using IRS-2 deficient mice ( IRS2(-/-) mice) and mechanisms of aggravation of type 2 diabetes due to modern diets were examined. IRS2(-/-) mice at 6 weeks of age were divided into three groups: Japanese diet (Jd) group, American diet (Ad) group and CA-1 diet [regular diet (Rd)] group. Each diet was given to the dams from 7 days before delivery. When the IRS2(-/-) mice reached 6 weeks of age, the glucose tolerance test (GTT), insulin tolerance test (ITT) and organ sampling were performed. The sampled organs and white adipose tissue were used for analysis of RNA, enzyme activity and tissues. In GTT and ITT, the Ad group showed worse glucose tolerance and insulin resistance than the Rd group. Impaired glucose tolerance of the Jd group was the same as that of the Rd group, but insulin resistance was worse than in the Rd group. These results were caused an increase in fat accumulation and adipocytes in the peritoneal cavity by lipogenic enzyme activity in the liver and muscle, and the increase in TNFalpha of hypertrophic adipocyte origin further aggravated insulin resistance and the increase in resistin also aggravated the impaired glucose tolerance, leading to aggravation of type 2 diabetes. The Japanese and American diets given to the IRS2(-/-) mice, which we developed, showed abnormal findings in some IRS2(-/-) mice but inhibited excessive reactions of insulin signals as diets used in ordinary nutritional management.
authors.affiliation: Central Institute for Experimental Animals, Kawasaki-shi, Kanagawa, Japan. hashimot@ciea.or.jp
authors.forename: H
authors.initials: H
authors.lastname: Hashimoto
authors.forename: T
authors.initials: T
authors.lastname: Arai
authors.forename: A
authors.initials: A
authors.lastname: Mori
authors.forename: K
authors.initials: K
authors.lastname: Kawai
authors.forename: K
authors.initials: K
authors.lastname: Hikishima
authors.forename: Y
authors.initials: Y
authors.lastname: Ohnishi
authors.forename: T
authors.initials: T
authors.lastname: Eto
authors.forename: M
authors.initials: M
authors.lastname: Ito
authors.forename: K
authors.initials: K
authors.lastname: Hioki
authors.forename: R
authors.initials: R
authors.lastname: Suzuki
authors.forename: M
authors.initials: M
authors.lastname: Ohsugi
authors.forename: M
authors.initials: M
authors.lastname: Saito
authors.forename: Y
authors.initials: Y
authors.lastname: Ueyama
authors.forename: H
authors.initials: H
authors.lastname: Okano
authors.forename: T
authors.initials: T
authors.lastname: Yamauchi
authors.forename: N
authors.initials: N
authors.lastname: Kubota
authors.forename: K
authors.initials: K
authors.lastname: Ueki
authors.forename: K
authors.initials: K
authors.lastname: Tobe
authors.forename: N
authors.initials: N
authors.lastname: Tamaoki
authors.forename: T
authors.initials: T
authors.lastname: Kadowaki
authors.forename: K
authors.initials: K
authors.lastname: Kosaka
mesh_terms: D052242:Adiponectin / Q000097:blood; D052436:Adipose Tissue, White / Q000378:metabolism; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight; D003921:Diabetes Mellitus, Experimental / Q000235:genetics / Q000378:metabolism*; D004032:Diet; D004041:Dietary Fats / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D005951:Glucose Tolerance Test; D007328:Insulin / Q000097:blood; D055504:Insulin Receptor Substrate Proteins / Q000235:genetics / Q000378:metabolism*; D007333:Insulin Resistance; D008099:Liver / Q000378:metabolism; D008279:Magnetic Resonance Imaging; D051379:Mice; D018482:Muscle, Skeletal / Q000378:metabolism; D010179:Pancreas / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D052242:Adiponectin; D001786:Blood Glucose; D004041:Dietary Fats; D007328:Insulin; D055504:Insulin Receptor Substrate Proteins; C526298:Irs2 protein, mouse