Reconsideration of Insulin Signals Induced by Improved Laboratory Animal Diets, Japanese and American Diets, in IRS-2 Deficient Mice

 

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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 TNFα 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.

References

• 1 Arai T, Machida Y, Sasaki M. et al . Hepatic enzyme activities and plasma insulin concentrations in diabetic voles.  Vet Res Commun. 1989;  13 421-426
  PubMedGoogle Scholar
• 2 Arai T, Hashimoto H, Kawai K. et al . Fulminant type 1 diabetes mellitus observed in insulin receptor substrate 2 deficient mice.  Clin Exp Med. 2008;  8 93-99
  CrossrefPubMedGoogle Scholar
• 3 Elias D, Markovits D, Reshef T. et al . Induction and therapy of autoimmune diabetes in the non-obese diabetic (NOD/Lt) mouse by a 65-kDa heat shock protein.  Proc Natl Acad Sci USA. 1990;  87 1576-1580
  CrossrefPubMedGoogle Scholar
• 4 Halestrap AP, Denton RM. Insulin and the regulation of adipose tissue acetyl-coenzyme A caroboxylase.  Biochem J. 1973;  132 509-517
  PubMedGoogle Scholar
• 5 Hashimoto H, Arai T, Takeguchi A. et al . Ontogenetic characteristics of enzyme activities and plasma metabolites in C57BL/6J:Jcl mice deficient in insulin receptor substrate 2.  Comp Med. 2006;  56 176-187
  PubMedGoogle Scholar
• 6 Hess B, Wieker HJ. Pyruvate kinase from yeast. In: Bergmeyer HU, Ed. Methods of Enzymatic Analysis. vol. 2. New York, Academic Press 1974: 778-763
  Google Scholar
• 7 Hotamisligil GS. The role of TNFalpha and TNF receptors in obesity and insulin resistance.  J Intern Med. 1999;  245 621-625
  CrossrefPubMedGoogle Scholar
• 8 Huggett AG, Nixon DA. Use of glucose oxidase, peroxidase and o-dianisidine in determination of blood and urinary glucose.  Lancet. 1957;  2 368-370
  PubMedGoogle Scholar
• 9 Inoue M, Ohtake T, Motomura W. et al . Increased expression of PPARgamma in high fat diet-induced liver steatosis in mice.  Biochem Biophys Res Commun. 2005;  336 , pp215–222 all
  PubMedGoogle Scholar
• 10 Jiang T, Wang Z, Proctor G. Diet-induced obesity in C57BL/6J mice causes increased renal lipid accumulation and glomerulosclerosis via a sterol regulatory element-binding protein-1c-dependent pathway.  J Biol Chem. 2005;  280 32317-32325
  CrossrefPubMedGoogle Scholar
• 11 Kadowaki T. Insights into insulin resistance and type 2 diabetes from knockout mouse models.  J Clin Invest. 2000;  106 459-465
  CrossrefPubMedGoogle Scholar
• 12 Kahn BB, Flier JS. Obesity and insulin resistance.  J Clin Invest. 2000;  106 473-481
  CrossrefPubMedGoogle Scholar
• 13 Kamei N, Tobe K, Suzuki R. et al . Overexpression of monocyte chemoattractant protein-1 in adipose tissues causes macrophage recruitment and insulin resistance.  J Biol Chem. 2006;  281 26602-26614
  CrossrefPubMedGoogle Scholar
• 14 Kubota N, Tobe K, Terauchi Y. et al . Disruption of insulin receptor substrate 2 causes type 2 diabetes because of liver insulin resistance and lack of compensatory beta-cell hyperplasia.  Diabetes. 2000;  49 1880-1889
  CrossrefPubMedGoogle Scholar
• 15 Margalit M, Shalev Z, Pappo O. et al . Glucocerebroside ameliorates the metabolic syndrome in OB/OB mice.  J Pharmacol Exp Ther. 2006;  319 105-110
  CrossrefPubMedGoogle Scholar
• 16 Martin BB, Denton RM. The intracellular localization of enzymes in white-adipose-tissue fat-cells and permeability properties of fat-cell mitochondria.  Biochem J. 1970;  117 861-877
  PubMedGoogle Scholar
• 17 Okumura T, Kohgo Y. Increased expression of PPargamma in fatty liver induced by high fat diet.  Nippon Rinsho. 2006;  64 1056-1061
  PubMedGoogle Scholar
• 18 Rej R, Horder M. Aspartate aminotransferase (glutamate oxaloacetate transaminase). In: Bergmeyer HU, Ed. Methods of Enzymatic Analysis, third edition. Verlag Chemie, New York 1983: pp 416-433
  Google Scholar
• 19 Rossmeisl M, Rim JS, Koza RA. et al . Variation in type 2 diabetes – related traits in mouse strains susceptible to diet-induced obesity.  Diabetes. 2003;  52 1958-1966
  CrossrefPubMedGoogle Scholar
• 20 Schadinger SE, Bucher NL, Schreiber BM. et al . PPARgamma2 regulates lipogenesis and lipid accumulation in steatotic hepatocytes.  J Physiol Endocrinol Metab. 2005;  288 E1195-E1205
  PubMedGoogle Scholar
• 21 Schroeder-Gloeckler JM, Rahman SM, Janssen RC. et al . CCAAT/enhancer-binding protein beta deletion reduces adiposity, hepatic steatosis, and diabetes in Lepr (db/db) mice.  J Biol Chem. 2007;  282 15717-15729
  CrossrefPubMedGoogle Scholar
• 22 Sesti G, Federici M, Hribal ML. et al . Defects of the insulin receptor substrate (IRS) system in human metabolic disorders.  FASEB J. 2001;  15 2099-2111
  CrossrefPubMedGoogle Scholar
• 23 Shimomura I, Bashmakov Y, Horton JD. Increased levels of nuclear SREBP-1c associated with fatty livers in two mouse models of diabetes mellitus.  J Biol Chem. 1999;  274 , pp30028–30032
  PubMedGoogle Scholar
• 24 Shimomura I, Hammer RE, Ikemoto S. et al . Leptin reverses insulin resistance and diabetes mellitus in mice with congenital lipodystrophy.  Nature. 1999;  401 73-76
  CrossrefPubMedGoogle Scholar
• 25 Shiota M, Postic C, Fujimoto Y. et al . Glucokinase gene locus transgenic mice are resistant to the development of obesity-induced type 2 diabetes.  Diabetes. 2001;  50 622-629
  CrossrefPubMedGoogle Scholar
• 26 Shulman GI. Cellular mechanisms of insulin resistance.  J Clin Invest. 2000;  106 171-176
  CrossrefPubMedGoogle Scholar
• 27 Steppan CM, Bailey ST, Bhat S. et al . The hormone resistin links obesity to diabetes.  Nature. 2001;  409 307-312
  CrossrefPubMedGoogle Scholar
• 28 Suzuki R, Tobe K, Aoyama M. et al . Both insulin signaling defects in the liver and obesity contribute to insulin resistance and cause diabetes in Irs2 ^−/− mice.  J Biol Chem. 2004;  279 25039-25049
  CrossrefPubMedGoogle Scholar
• 29 Takahashi M, Ikemoto S, Ezaki O. Effect of the Fat/Carbohydrate ratio in the diet on obesity and oral glucose tolerance in C57BL/6J mice.  J Nutr Sci Vitaminol. 1999;  45 583-593
  CrossrefPubMedGoogle Scholar
• 30 Takeda Y, Suzuki F, Inoue H. ATP citrate lyase (Citrate cleavage enzyme). In: Lowenstein JM, Ed. Methods in Enzymology. 1969 vol. 13 Academic Press, New York pp.153- 160
  Google Scholar
• 31 Terauchi Y, Iwamoto K, Tamemoto H. et al . Development of non-insulin-dependent diabetes mellitus in the double knockout mice with disruption of insulin receptor substrate-1 and beta cell glucokinase genes. Genetic reconstitution of diabetes as a polygenic disease.  J Clin Invest. 1997;  99 861-866
  CrossrefPubMedGoogle Scholar
• 32 Tobe K, Suzuki R, Aoyama M. et al . Increased expression of the sterol regulatory element-binding protein-1 gene in insulin receptor substrate-2 (−/−) mouse liver.  J Biol Chem. 2001;  19 38337-38340
  PubMedGoogle Scholar
• 33 Tsuji A, Torres-Rosado A, Arai T. et al . Hepsin, a cell membrane-associated protease. Characterization, tissue distribution and gene localization.  J Biol Chem. 266 1991;  16948-16953
  PubMedGoogle Scholar
• 34 Vinuela E, Salas M, Sols A. Glucokinase and hexokinase in liver in relation to glycogen synthesis.  J Biol Chem. 1963;  238 PC1175-PC1177
  PubMedGoogle Scholar
• 35 Wang YX, Lee CH, Tiep S. et al . Peroxisome-proliferator-activated receptor delta activates fat metabolism to prevent obesity.  Cell. 2003;  113 , pp159–170
  PubMedGoogle Scholar
• 36 Wang Z, Jiang T, Li J. et al . Regulation of renal lipid metabolism, lipid accumulation, and glomerulosclerosis in FVBdb/db mice with type 2 diabetes.  Diabetes. 2005;  54 , pp2328–2335
  PubMedGoogle Scholar
• 37 Zimmet P, Alberti K, Shaw J. Global and societal implications of the diabetes epidemic.  Nature. 2001;  414 782-787
  CrossrefPubMedGoogle Scholar

Correspondence

H. Hashimoto

Department of Laboratory Animal Research

Central Institute for Experimental Animals

Phone: +044/754/44 85

Fax: +044/751/88 10

Email: hashimot@ciea.or.jp