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.

Vinyl Isolator Breeding Induces Insulin Resistance in C57BL/6JJcl Mice

“…deficient mouse given a high fat diet developed impaired glucose tolerance from insulin resistance dependent on the fat content of the diet [14]. Because the hyperinsulinemia occurred in the SPF group and the insulin concentration in the GF group was basically the same as that in the Conv group, the impaired glucose tolerance found in the GF and SPF groups was not considered to be caused by an insulin secretory defect but by an increase in blood glucose concentrations due to strong insulin resistance.…”

Study on Establishment of Congenic Strains and Screening of Characteristics in IRS-2 Deficient Mice to Support Translational Research on Type 2 Diabetes

“…Data for the B6J-Irs2 -/-mouse are presented in this paper. The descriptions and data in the following sections are cited and abstracted from previous publications [2,[7][8][9][10].…”

“…When research on the ontogenetic characteristics of B6J-Irs2 -/-mice began, Kagohashi et al of Shimane Univer-sity reported that onset of type 1 diabetes in NOD mice produced by embryo transplants into ICR or DBA/2J recipients was later than that in NOD mice reared by foster mothers [17]. The B6J-Irs2 -/-mice used in the investigation of ontogenetic characteristics [7] were prepared by in vitro fertilization and embryo transfer. -/-(D1-3) mice sera reacted with pancreatic sections.…”

Fulminant Type 1 Diabetes Mellitus in IRS-2 Deficient Mice

“…Effects of modern Japanese and American diets on RNA expression of GLUT4 and PPAR 2 of adipose tissues and plasma adipocytokines concentrations in IRS-2 deficient mice fed with three kinds of diets with different lipid levels. regular and Japanese and American diets as well as tap water ad libitum for 2 weeks, and used for glucose tolerance test, insulin tolerance test, and harvests of blood, liver, femoral muscles, white adipose tissue (WAT), and pancreas for chemical analysis at the age of 6 weeks (Hashimoto et al, 2009). Average body weight of Rd, Jd and Ad group at 6 week of age were 20.8, 22.7 and 22.9g each.…”