inbred oletf rats


Summary: An inbred strain of Long-Evans rats that develops hyperglycemia, hyperinsulinemia, and mild obesity, mostly in males, that resembles non-insulin-dependent diabetes mellitus in humans. It was developed from outbred Long-Evans stock in 1983.

Top Publications

  1. Moralejo D, Ogino T, Zhu M, Toide K, Wei S, Wei K, et al. A major quantitative trait locus co-localizing with cholecystokinin type A receptor gene influences poor pancreatic proliferation in a spontaneously diabetogenic rat. Mamm Genome. 1998;9:794-8 pubmed
    ..The QTL co-localizes with the gene encoding cholecystokinin type A receptor (CCKAR) which is likely to mediate the trophic effect of cholecystokinin on pancreas and is defective in the OLETF rat...
  2. Watanabe T, Okuno S, Oga K, Mizoguchi Miyakita A, Tsuji A, Yamasaki Y, et al. Genetic dissection of "OLETF," a rat model for non-insulin-dependent diabetes mellitus: quantitative trait locus analysis of (OLETF x BN) x OLETF. Genomics. 1999;58:233-9 pubmed
    ..16, for postprandial glucose level) and the other on chromosome X (Dmo11/Odb1: LOD = 7.81, for postprandial glucose level). These data are comparable to results of our previous studies of the OLETF rat...
  3. Murata I, Takemura G, Asano K, Sano H, Fujisawa K, Kagawa T, et al. Apoptotic cell loss following cell proliferation in renal glomeruli of Otsuka Long-Evans Tokushima Fatty rats, a model of human type 2 diabetes. Am J Nephrol. 2002;22:587-95 pubmed
    ..The mechanism of glomerular cell loss during the late stage of diabetic nephropathy is unknown...
  4. Chen H, Higashino H, Kamenov Z, Azuma M, Lee W, Yang X, et al. Preserved postischemic heart function in sucrose-fed type 2 diabetic OLETF rats. Life Sci. 2003;72:2839-51 pubmed
    ..Less norepinephrine release may play a role in preventing postischemic functional deterioration in sucrose-fed diabetic hearts...
  5. Saito F, Kawaguchi M, Izumida J, Asakura T, Maehara K, Maruyama Y. Alteration in haemodynamics and pathological changes in the cardiovascular system during the development of Type 2 diabetes mellitus in OLETF rats. Diabetologia. 2003;46:1161-9 pubmed
    ..We investigated pathophysiological changes of the heart and vessels in the Otsuka Long-Evans Tokushima Fatty (OLETF) rat Type 2 DM model during a long time period...
  6. Koh E, Kim M, Park J, Kim H, Youn J, Park H, et al. Peroxisome proliferator-activated receptor (PPAR)-alpha activation prevents diabetes in OLETF rats: comparison with PPAR-gamma activation. Diabetes. 2003;52:2331-7 pubmed
  7. Hayashi T, Sohmiya K, Ukimura A, Endoh S, Mori T, Shimomura H, et al. Angiotensin II receptor blockade prevents microangiopathy and preserves diastolic function in the diabetic rat heart. Heart. 2003;89:1236-42 pubmed
    ..Cardiac microangiopathy may be involved in the development of heart failure in diabetes mellitus...
  8. Moran T, Bi S. Hyperphagia and obesity in OLETF rats lacking CCK-1 receptors. Philos Trans R Soc Lond B Biol Sci. 2006;361:1211-8 pubmed
    ..The OLETF rat is a valuable model for characterizing actions of CCK in energy balance and has provided novel insights into interactions between exercise and food intake...
  9. Lee H, Choi S, Park M, An Y, Seo S, Kim M, et al. Fenofibrate lowers abdominal and skeletal adiposity and improves insulin sensitivity in OLETF rats. Biochem Biophys Res Commun. 2002;296:293-9 pubmed
    ..It might result in reduction of adiposity of truncal adipose tissue and skeletal muscle. We suggest that reduction of adiposity in trunk and skeletal muscle might improve insulin sensitivity...

More Information

Publications109 found, 100 shown here

  1. Huang Q, Bu S, Yu Y, Guo Z, Ghatnekar G, Bu M, et al. Diazoxide prevents diabetes through inhibiting pancreatic beta-cells from apoptosis via Bcl-2/Bax rate and p38-beta mitogen-activated protein kinase. Endocrinology. 2007;148:81-91 pubmed
  2. Kim Y, Choi M, Kim Y, Han J, Lee J, Park C, et al. Protein kinase C delta regulates anti-apoptotic alphaB-crystallin in the retina of type 2 diabetes. Neurobiol Dis. 2007;28:293-303 pubmed
    ..These changes were abolished by rottlerin treatment, a highly specific PKC delta inhibitor. These results suggest that PKC delta is involved in regulation of anti-apoptotic function of alphaBC in the retina of type 2 diabetes...
  3. Sugiura K, Miyake T, Taniguchi Y, Yamada T, Moralejo D, Wei S, et al. Identification of novel non-insulin-dependent diabetes mellitus susceptibility loci in the Otsuka Long-Evans Tokushima fatty rat by MQM-mapping method. Mamm Genome. 1999;10:1126-31 pubmed
    ..There is epistatic interaction between Nidd2 and 14/of. Additionally, our results indicated that the novel QTLs could show no linkage with body weight, but Nidd12/of has an interaction with body weight. ..
  4. Li C, Yang C, Park C, Ahn H, Kim W, Yoon K, et al. Long-term treatment with ramipril attenuates renal osteopontin expression in diabetic rats. Kidney Int. 2003;63:454-63 pubmed
  5. Watanabe T, Suzuki M, Yamasaki Y, Okuno S, Hishigaki H, Ono T, et al. Mutated G-protein-coupled receptor GPR10 is responsible for the hyperphagia/dyslipidaemia/obesity locus of Dmo1 in the OLETF rat. Clin Exp Pharmacol Physiol. 2005;32:355-66 pubmed
    ..5. Taken together, these results demonstrate that the mutated GPR10 receptor is responsible for the hyperphagia leading to obesity and dyslipidaemia in the obese diabetic strain rat. ..
  6. Mori Y, Nakagiri H, Kondo H, Murase T, Tokimitsu I, Tajima N. Dietary diacylglycerol reduces postprandial hyperlipidemia and ameliorates glucose intolerance in Otsuka Long-Evans Tokushima Fatty (OLETF) rats. Nutrition. 2005;21:933-9 pubmed
    ..05). These results suggested that dietary DG improves lipid metabolism and glucose tolerance, and retards the progress of diabetes mellitus in OLETF rats. ..
  7. Aoyama I, Shimokata K, Niwa T. An oral adsorbent downregulates renal expression of genes that promote interstitial inflammation and fibrosis in diabetic rats. Nephron. 2002;92:635-51 pubmed
    ..AST-120 ameliorates tubulointerstitial injury by reducing renal expression of ICAM-1, osteopontin, MCP-1, TGF-beta1 and clusterin in 1/2NxOLETF rats. ..
  8. Ivanov A, Kulchitsky V, Romanovsky A. Role for the cholecystokinin-A receptor in fever: a study of a mutant rat strain and a pharmacological analysis. J Physiol. 2003;547:941-9 pubmed
    ..None of the three known phases of the febrile response of rats to LPS requires the CCK-A receptor. ..
  9. Nagai Y, Yao L, Kobori H, Miyata K, Ozawa Y, Miyatake A, et al. Temporary angiotensin II blockade at the prediabetic stage attenuates the development of renal injury in type 2 diabetic rats. J Am Soc Nephrol. 2005;16:703-11 pubmed
    ..These data suggest that early AngII blockade could be an effective strategy for preventing the development of type 2 diabetic renal injury later in life. ..
  10. Hajnal A, Margas W, Covasa M. Altered dopamine D2 receptor function and binding in obese OLETF rat. Brain Res Bull. 2008;75:70-6 pubmed
    ..These findings demonstrate an altered D2R signaling in obese OLETF rats similar to drug-induced sensitization and suggest a link between this effect and avidity for sucrose in this model. ..
  11. Yoshiji H, Noguchi R, Kaji K, Ikenaka Y, Shirai Y, Namisaki T, et al. Attenuation of insulin-resistance-based hepatocarcinogenesis and angiogenesis by combined treatment with branched-chain amino acids and angiotensin-converting enzyme inhibitor in obese diabetic rats. J Gastroenterol. 2010;45:443-50 pubmed publisher
    ..Because both BCAAs and ACE-Is are widely used in clinical practice, this combination therapy may represent a potential new strategy for chemoprevention against IR-based HCC in the future. ..
  12. Schroeder M, Weller A. Anxiety-like behavior and locomotion in CCK1 knockout rats as a function of strain, sex and early maternal environment. Behav Brain Res. 2010;211:198-207 pubmed publisher
  13. Jia D, Fukumitsu K, Tabaru A, Akiyama T, Otsuki M. Troglitazone stimulates pancreatic growth in congenitally CCK-A receptor-deficient OLETF rats. Am J Physiol Regul Integr Comp Physiol. 2001;280:R1332-40 pubmed
  14. Katsuragi I, Okeda T, Yoshimatsu H, Utsunomiya N, Ina K, Sakata T. Transplantation of normal islets into the portal vein of Otsuka Long Evans Tokushima Fatty rats prevents diabetic progression. Exp Biol Med (Maywood). 2001;226:681-5 pubmed
  15. Sugimoto K, Tsuruoka S, Fujimura A. Renal protective effect of YM598, a selective endothelin ET(A) receptor antagonist, against diabetic nephropathy in OLETF rats. Eur J Pharmacol. 2002;450:183-9 pubmed
    ..These data suggest that endothelin is involved in the progression of diabetic nephropathy in Otsuka Long-Evans Tokushima Fatty rats, and an endothelin ET(A) receptor antagonist may be useful for the treatment of diabetic nephropathy. ..
  16. Mizushige T, Mizushige K, Miyatake A, Kishida T, Ebihara K. Inhibitory effects of soy isoflavones on cardiovascular collagen accumulation in rats. J Nutr Sci Vitaminol (Tokyo). 2007;53:48-52 pubmed
  17. Guo Z, Bu S, Yu Y, Ghatnekar G, Wang M, Chen L, et al. Diazoxide prevents abdominal adiposity and fatty liver in obese OLETF rats at prediabetic stage. J Diabetes Complications. 2008;22:46-55 pubmed publisher
    ..These metabolic changes may occur through a direct effect on beta-cells through reduction of their workload and suppression of insulin secretion. ..
  18. Kim H, Noh J, Hong S, Hwang Y, Yang T, Lee M, et al. Rosiglitazone stimulates the release and synthesis of insulin by enhancing GLUT-2, glucokinase and BETA2/NeuroD expression. Biochem Biophys Res Commun. 2008;367:623-9 pubmed publisher
    ..These results suggest that RGZ could stimulate the release and synthesis of insulin through the upregulation of GLUT-2, GCK, and BETA2/NeuroD gene expression. ..
  19. Matsuzaki G, Ishizaka N, Furuta K, Hongo M, Saito K, Sakurai R, et al. Comparison of vasculoprotective effects of benidipine and losartan in a rat model of metabolic syndrome. Eur J Pharmacol. 2008;587:237-42 pubmed publisher
    ..These data suggest that, when used in an antihypertensive dose, benidipine is as effective as losartan in restoring vascular endothelial function and in suppressing of cardiovascular remodeling in an animal model of metabolic syndrome. ..
  20. Matsumoto T, Ishida K, Kobayashi T, Kamata K. Pyrrolidine dithiocarbamate reduces vascular prostanoid-induced responses in aged type 2 diabetic rat model. J Pharmacol Sci. 2009;110:326-33 pubmed
    ..These results suggest that PDTC has beneficial effects against the abnormal vasoconstrictor prostanoid signaling present in rats at the chronic stage of type 2 diabetes. ..
  21. Jesmin S, Sakuma I, Hattori Y, Kitabatake A, Miyauchi T. The calcium channel antagonist benidipine reduces plasma and cardiac endothelin-1 levels in type II diabetic rat model. J Cardiovasc Pharmacol. 2004;44 Suppl 1:S49-53 pubmed
    ..Our results suggest that ET-1 plays a pivotal role in the pathogenesis of cardiac complications at the insulin-resistant stage of diabetes mellitus, and that benidipine treatment may have a beneficial effect on these complications. ..
  22. Watanabe A, Okuno S, Okano M, Jordan S, Aihara K, Watanabe T, et al. Altered emotional behaviors in the diabetes mellitus OLETF type 1 congenic rat. Brain Res. 2007;1178:114-24 pubmed
    ..On the basis of these observations, the GPR10 might be a novel target for the developing new drugs against anxiety and/or other stress-related diseases. ..
  23. Schroeder M, Lavi Avnon Y, Zagoory Sharon O, Moran T, Weller A. Preobesity in the infant OLETF rat: the role of suckling. Dev Psychobiol. 2007;49:685-91 pubmed
    ..OLETF dams increased their average nursing time over the PN weeks, while control dams decreased their nursing time toward weaning. The results suggest an important contribution of OLETF pups toward their own preobese development. ..
  24. Sasaki H, Ogawa K, Shimizu M, Mori C, Takatsuka H, Okazaki F, et al. The insulin sensitizer pioglitazone improves the deterioration of ischemic preconditioning in type 2 diabetes mellitus rats. Int Heart J. 2007;48:623-35 pubmed
    ..The insulin sensitizer pioglitazone can improve the deterioration of IP against reperfusion arrhythmias in type 2 diabetic rats. ..
  25. Miyasaka K, Funakoshi A. Is the OLETF rat a good model of central sensitization?. J Pharmacol Sci. 2007;105:373 pubmed
  26. Rahman S, Wang Y, Yotsumoto H, Cha J, Han S, Inoue S, et al. Effects of conjugated linoleic acid on serum leptin concentration, body-fat accumulation, and beta-oxidation of fatty acid in OLETF rats. Nutrition. 2001;17:385-90 pubmed
    ..Serum concentrations of non-esterified fatty acid and TG also were reduced in rats fed diets supplemented with TG-CLA and FFA-CLA. ..
  27. Jesmin S, Sakuma I, Salah Eldin A, Nonomura K, Hattori Y, Kitabatake A. Diminished penile expression of vascular endothelial growth factor and its receptors at the insulin-resistant stage of a type II diabetic rat model: a possible cause for erectile dysfunction in diabetes. J Mol Endocrinol. 2003;31:401-18 pubmed
    ..We propose that the abnormalities of the VEGF signaling system in the penis may play a role in the pathophysiology of diabetic ED. ..
  28. Watanabe T, Okuno S, Yamasaki Y, Ono T, Oga K, Mizoguchi Miyakita A, et al. A < 1.7 cM interval is responsible for Dmo1 obesity phenotypes in OLETF rats. Clin Exp Pharmacol Physiol. 2004;31:110-2 pubmed
    ..11). One LOD support interval lies within the < 1.7 cM region between D1Rat461 and D1Rat459. 5. This large intercross study confirms that Dmo1 is likely localized within the interval. ..
  29. Onozaki A, Midorikawa S, Sanada H, Hayashi Y, Baba T, Katoh T, et al. Rapid change of glucose concentration promotes mesangial cell proliferation via VEGF: inhibitory effects of thiazolidinedione. Biochem Biophys Res Commun. 2004;317:24-9 pubmed
    ..These findings indicate that a rapid change of glucose concentration promotes RMC proliferation by the increased production of VEGF. TZD has an inhibitory action through, at least in part, PPAR-gamma. ..
  30. Jia D, Taguchi M, Otsuki M. Synthetic protease inhibitor camostat prevents and reverses dyslipidemia, insulin secretory defects, and histological abnormalities of the pancreas in genetically obese and diabetic rats. Metabolism. 2005;54:619-27 pubmed
  31. Swartz T, Hajnal A, Covasa M. Altered orosensory sensitivity to oils in CCK-1 receptor deficient rats. Physiol Behav. 2010;99:109-17 pubmed publisher
    ..Collectively, these results show that increased oil intake in OLETF rats is driven by both peripheral deficits to satiation and altered orosensory sensitivity. ..
  32. Okamoto S, Shimizu M, Mizuno A, Higuchi T. Estrogens inhibit food intake in CCK-1 receptor-deficient rats. J Physiol Sci. 2010;60:267-71 pubmed publisher
    ..These results suggest that the anorexigenic and hyper-active effects of estrogen can be mediated via pathways other than CCK-CCK1 receptor signaling pathway in CCK1 receptor-deficient rats. ..
  33. Feifel D, Shilling P, Kuczenski R, Segal D. Altered extracellular dopamine concentration in the brains of cholecystokinin-A receptor deficient rats. Neurosci Lett. 2003;348:147-50 pubmed
    ..These findings suggest that CCK-A receptors play an important role in the regulation of central DA transmission, and support the notion that the OLETF rat is a useful model to study this regulation. ..
  34. Muramatsu Y, Taniguchi Y, Kose H, Matsumoto K, Yamada T, Sasaki Y. Capn10, a candidate gene responsible for type 2 diabetes mellitus in the OLETF rat. IUBMB Life. 2003;55:533-7 pubmed
    ..This non-conservative amino acid substitution might be associated with susceptibility to type 2 diabetes in OLETF rats. ..
  35. Choi S, Zhao Z, Lee Y, Kim S, Kim D, Ahn C, et al. The different mechanisms of insulin sensitizers to prevent type 2 diabetes in OLETF rats. Diabetes Metab Res Rev. 2007;23:411-8 pubmed
    ..The reversal of dyslipidaemia and the fat redistribution might contribute to the greater improvement of pioglitazone treatment compared to metformin in OLETF rats. ..
  36. Zhao J, Zhang N, He M, Yang Z, Tong W, Wang Q, et al. Increased beta-cell apoptosis and impaired insulin signaling pathway contributes to the onset of diabetes in OLETF rats. Cell Physiol Biochem. 2008;21:445-54 pubmed publisher
    ..Our findings suggest that despite increasing beta-cell mass the impaired beta-cell insulin signaling and reduced beta-cell insulin content may contribute to the onset of overt diabetes in OLETF rats. ..
  37. Schroeder M, Shbiro L, Gelber V, Weller A. Post-weaning voluntary exercise exerts long-term moderation of adiposity in males but not in females in an animal model of early-onset obesity. Horm Behav. 2010;57:496-505 pubmed publisher
    ..Findings expose sex-dependent peripheral mechanisms in coping with energy challenges. ..
  38. Shilling P, Feifel D. Decreased haloperidol-induced potentiation of zif268 mRNA expression in the nucleus accumbens shell and the dorsal lateral striatum of rats lacking cholecystokinin-A receptors. Synapse. 2002;43:134-8 pubmed
    ..05), but not in the NA core, in OLETF rats compared to LETO rats. These data suggest that CCK-A receptor mechanisms may contribute to the therapeutic and the extrapyramidal motor effects associated with antipsychotic drug treatment. ..
  39. Nagao K, Inoue N, Wang Y, Hirata J, Shimada Y, Nagao T, et al. The 10trans,12cis isomer of conjugated linoleic acid suppresses the development of hypertension in Otsuka Long-Evans Tokushima fatty rats. Biochem Biophys Res Commun. 2003;306:134-8 pubmed
    ..We speculate that the antihypertensive effect of 10t,12c-CLA can be attributed to the lowered secretion of hypertensive adipocytokines from abdominal adipose tissues. ..
  40. Jia D, Taguchi M, Otsuki M. Preventive and therapeutic effects of the protease inhibitor camostat on pancreatic fibrosis and atrophy in CCK-1 receptor-deficient rats. Pancreas. 2005;30:54-61 pubmed
    ..The results of the present study suggest that camostat greatly inhibits pancreatic inflammation and prevents and reverses fibrosis and atrophy of the pancreas in the genetically obese and CCK-1 receptor-deficient OLETF rats. ..
  41. Cha D, Kang Y, Han S, Jee Y, Han K, Kim H, et al. Role of aldosterone in diabetic nephropathy. Nephrology (Carlton). 2005;10 Suppl:S37-9 pubmed
    ..These results suggest that aldosterone blockade could play a role in preventing the progression of diabetic nephropathy via anti-inflammatory and antifibrotic mechanisms. ..
  42. Matsumoto T, Kobayashi T, Kamata K. Mechanisms underlying the impaired EDHF-type relaxation response in mesenteric arteries from Otsuka Long-Evans Tokushima Fatty (OLETF) rats. Eur J Pharmacol. 2006;538:132-40 pubmed
    ..We conclude that the impairment of EDHF-type relaxation seen in OLETF rats may be attributable not only to a reduction in cAMP/PKA signaling, but also to reduced endothelial K(Ca) channel activities. ..
  43. Kose H, Bando Y, Izumi K, Yamada T, Matsumoto K. Epistasis between hyperglycemic QTLs revealed in a double congenic of the OLETF rat. Mamm Genome. 2007;18:609-15 pubmed
    ..These results indicate that there is an epistatic interaction between the two loci. However, it is unlikely that the abnormal level of enhanced glucose homeostasis is mediated, at least not directly, by leptin or fat mass. ..
  44. Matsumoto M, Tsujino T, Naito Y, Sakoda T, Ohyanagi M, Nonaka H, et al. High salt intake elevated blood pressure but not changed circadian blood pressure rhythm in Otsuka Long-Evans Tokushima Fatty (OLETF) rat. Clin Exp Hypertens. 2009;31:271-80 pubmed publisher
    ..High salt intake elevated blood pressure and exacerbated hyperinsulinemia, but did not change the circadian blood pressure rhythm in OLETF rats. ..
  45. Nakaya Y, Minami A, Harada N, Sakamoto S, Niwa Y, Ohnaka M. Taurine improves insulin sensitivity in the Otsuka Long-Evans Tokushima Fatty rat, a model of spontaneous type 2 diabetes. Am J Clin Nutr. 2000;71:54-8 pubmed
  46. Beinfeld M, Connolly K, Pierce R. OLETF (Otsuka Long-Evans Tokushima Fatty) rats that lack the CCK 1 (A) receptor develop less behavioral sensitization to repeated cocaine treatment than wild type LETO (Long Evans Tokushima Otsuka) rats. Peptides. 2001;22:1285-90 pubmed
    ..These results support the hypothesis that endogenous CCK released by cocaine treatment and acting at CCK 1 receptors is required for the development and/or expression of this behavior. ..
  47. MacMurray A, Moralejo D, Kwitek A, Rutledge E, Van Yserloo B, Gohlke P, et al. Lymphopenia in the BB rat model of type 1 diabetes is due to a mutation in a novel immune-associated nucleotide (Ian)-related gene. Genome Res. 2002;12:1029-39 pubmed
    ..The lymphopenia mutation may thus be useful not only to elucidate Type 1 diabetes, but also in the function of the Ian gene family as a whole...
  48. Felix F, Fontenele J. The OLETF rat as a model of central sensitization: possible relevance to the study of fibromyalgia and related diseases. J Pharmacol Sci. 2007;105:372 pubmed
  49. Zamami Y, Fujiwara H, Hosoda M, Hino H, Hirai K, Okamoto K, et al. [Ameliorative effect of propolis on insulin resistance in Otsuka Long-Evans Tokushima Fatty (OLETF) rats]. Yakugaku Zasshi. 2010;130:833-40 pubmed
    ..These results suggest that propolis could be an effective and functional food to prevent development of insulin resistance. ..
  50. Nomoto S, Ohta M, Kanai S, Yoshida Y, Takiguchi S, Funakoshi A, et al. Absence of the cholecystokinin-A receptor deteriorates homeostasis of body temperature in response to changes in ambient temperature. Am J Physiol Regul Integr Comp Physiol. 2004;287:R556-61 pubmed
    ..Mice without CCK-AR showed larger hysteresis than mice with CCK-AR. From these results, we conclude that the lack of CCK-AR causes homeostasis of T(c) in rats and mice to deteriorate...
  51. Matsumoto T. [Therapeutic target for endothelium-derived hyperpolarizing factor signaling in diabetic vascular complication]. Yakugaku Zasshi. 2010;130:777-84 pubmed
    ..g., by inhibiting PDE3 activity) or reducing EDCFs signaling has potential as an interesting therapeutic target in diabetic vasculopathy...
  52. Wei S, Wei K, Moralejo D, Ogino T, Koike G, Jacob H, et al. Mapping and characterization of quantitative trait loci for non-insulin-dependent diabetes mellitus with an improved genetic map in the Otsuka Long-Evans Tokushima fatty rat. Mamm Genome. 1999;10:249-58 pubmed
  53. Moran T. Cholecystokinin and satiety: current perspectives. Nutrition. 2000;16:858-65 pubmed
  54. Nakamura J, Hamada Y, Sakakibara F, Hara T, Wakao T, Mori K, et al. Physiological and morphometric analyses of neuropathy in sucrose-fed OLETF rats. Diabetes Res Clin Pract. 2001;51:9-20 pubmed
  55. Abe T, Ohga Y, Tabayashi N, Kobayashi S, Sakata S, Misawa H, et al. Left ventricular diastolic dysfunction in type 2 diabetes mellitus model rats. Am J Physiol Heart Circ Physiol. 2002;282:H138-48 pubmed
    ..001) lower in severe DM rats. We conclude that the only lusitropic dysfunction due to the depressed expression of SERCA2 is related to generating diabetic cardiomyopathy even in the present type 2 diabetic rats...
  56. Shinomiya K, Fukunaga M, Kiyomoto H, Mizushige K, Tsuji T, Noma T, et al. A role of oxidative stress-generated eicosanoid in the progression of arteriosclerosis in type 2 diabetes mellitus model rats. Hypertens Res. 2002;25:91-8 pubmed
    ..8-iso-PGF2alpha may play an important role in the progression of arteriosclerosis. Antioxidant treatment may promise significant clinical benefits in the early diabetic stage...
  57. Uchida Y, Ohba K, Yoshioka T, Irie K, Muraki T, Maru Y. Cellular carbonyl stress enhances the expression of plasminogen activator inhibitor-1 in rat white adipocytes via reactive oxygen species-dependent pathway. J Biol Chem. 2004;279:4075-83 pubmed
    ..These results suggest that cellular carbonyl stress induced by AGEs or HNE may stimulate PAI-1 synthesis in and release from adipose tissues through ROS formation...
  58. De Jonghe B, Di Martino C, Hajnal A, Covasa M. Brief intermittent access to sucrose differentially modulates prepulse inhibition and acoustic startle response in obese CCK-1 receptor deficient rats. Brain Res. 2005;1052:22-7 pubmed
    ..A similar effect may be contributory to the hyperphagic behavioral phenotype of obese animal models with altered central dopamine regulation...
  59. Yamamoto M, Otsuki M. Effect of inhibition of alpha-glucosidase on age-related glucose intolerance and pancreatic atrophy in rats. Metabolism. 2006;55:533-40 pubmed
    ..Our study suggests that acarbose is useful in the prevention of age-related glucose intolerance and pancreatic atrophy...
  60. Tomiyoshi Y, Sakemi T, Aoki S, Miyazono M. Different effects of castration and estrogen administration on glomerular injury in spontaneously hyperglycemic Otsuka Long-Evans Tokushima Fatty (OLETF) rats. Nephron. 2002;92:860-7 pubmed
    ..However, there have been no detailed studies on the effects of castration and sex hormone in the development of diabetic nephropathy...
  61. Seo H, Kim Y, Lee K, Min A, Kim M, Kim H, et al. Endoplasmic reticulum stress-induced activation of activating transcription factor 6 decreases insulin gene expression via up-regulation of orphan nuclear receptor small heterodimer partner. Endocrinology. 2008;149:3832-41 pubmed publisher
    ..Collectively, this study shows that ER stress-induced activation of ATF6 plays an important role in the development of beta-cell dysfunction...
  62. Schroeder M, Schechter M, Fride E, Moran T, Weller A. Examining maternal influence on OLETF rats' early overweight: insights from a cross-fostering study. Dev Psychobiol. 2009;51:358-66 pubmed publisher
    ..Additionally, interaction between OLETF dams and pups produces high nursing frequency, exposing the pups to abundant high-fat milk, thus strengthening their preobese phenotype...
  63. Matsumoto T, Ozawa Y, Taguchi K, Kobayashi T, Kamata K. Chronic treatment with losartan (angiotensin II type 1 receptor antagonist) normalizes enhanced acetylcholine-induced coronary vasoconstriction in isolated perfused hearts of type 2 diabetic OLETF rats. J Smooth Muscle Res. 2009;45:197-208 pubmed
  64. Sato T, Niikawa J, Usui I, Imamura T, Yoshida H, Tanaka S, et al. Pancreatic regeneration after ethionine-induced acute pancreatitis in rats lacking pancreatic CCK-A receptor gene expression. J Gastroenterol. 2003;38:672-80 pubmed
    ..We used Otsuka Long-Evans Tokushima Fatty (OLETF) rats, a model lacking pancreatic CCK-A receptor gene expression...
  65. Matsushita H, Akiyoshi J, Kai K, Ishii N, Kodama K, Tsutsumi T, et al. Spatial memory impairment in OLETF rats without cholecystokinin - a receptor. Neuropeptides. 2003;37:271-6 pubmed
    ..In PA, OLETF rats did not show facilitating response 24 h after training. From these observations, we concluded that a spatial memory was impaired in the OLETF rats...
  66. Koike T, Tomoda F, Kinuno H, Inoue H, Takata M. Abnormal renal structural alterations during the development of diabetes mellitus in Otsuka Long-Evans Tokushima Fatty rats. Acta Physiol Scand. 2005;184:73-81 pubmed
    ..The aim of this study was to investigate the renal structural properties in diabetic nephropathy...
  67. Noguchi S, Ohno Y, Aoki N. Adrenocortical insufficiency in Otsuka Long-Evans Tokushima Fatty rats, a type 2 diabetes mellitus model. Metabolism. 2007;56:1326-33 pubmed
    ..We showed that adrenocortical insufficiency and adrenal atrophy were acquired in OLETF rats, and the possibility of elevated serum leptin relates to this phenomenon...
  68. Zagoory Sharon O, Schroeder M, Levine A, Moran T, Weller A. Adaptation to lactation in OLETF rats lacking CCK-1 receptors: body weight, fat tissues, leptin and oxytocin. Int J Obes (Lond). 2008;32:1211-21 pubmed publisher
    ..To understand the adaptation to lactation of obese rats, by studying the interplay among the gut hormone cholecystokinin (CCK), the adiposity hormone leptin and the affiliation hormone oxytocin in modulating body mass and fat storage...
  69. Yao L, Mizushige K, Noma T, Murakami K, Ohmori K, Matsuo H. Improvement of left ventricular diastolic dynamics in prediabetic stage of a type II diabetic rat model after troglitazone treatment. Angiology. 2001;52:53-7 pubmed
    ..0216). The data suggest that troglitazone improves left ventricular diastolic dynamics of a DM rat model at prediabetic stage...
  70. El Mahmoudy A, Matsuyama H, Borgan M, Shimizu Y, el Sayed M, Minamoto N, et al. Thymoquinone suppresses expression of inducible nitric oxide synthase in rat macrophages. Int Immunopharmacol. 2002;2:1603-11 pubmed
    ..These results suggest that TQ suppresses the production of NO by macrophages; an effect which may be useful in ameliorating the inflammatory and autoimmune conditions...
  71. Miyasaka K, Kanai S, Ohta M, Funakoshi A. Stimulatory effect of ethanol on pancreatic secretion in conscious rats requires CCK-A receptor. Pancreas. 2005;30:e22-8 pubmed
    ..To elucidate the mechanism, we examined whether ethanol influences pancreatic secretion in CCK-A receptor-deficient rats...
  72. Matsumoto T, Kobayashi T, Kamata K. Mechanisms underlying lysophosphatidylcholine-induced potentiation of vascular contractions in the Otsuka Long-Evans Tokushima Fatty (OLETF) rat aorta. Br J Pharmacol. 2006;149:931-41 pubmed
    ..The effect of lysophosphatidylcholine (LPC) on aortic contractions in Otsuka Long-Evans Tokushima Fatty (OLETF) rats, a type 2 diabetic model, was studied...
  73. Bi S, Chen J, Behles R, Hyun J, Kopin A, Moran T. Differential body weight and feeding responses to high-fat diets in rats and mice lacking cholecystokinin 1 receptors. Am J Physiol Regul Integr Comp Physiol. 2007;293:R55-63 pubmed
    ..Together, these data provide further evidence for differential roles of CCK1 receptors in the controls of food intake and body weight in rats and mice...
  74. Anzawa R, Seki S, Horikoshi K, Taniguchi M, Mochizuki S. Exacerbation of acidosis during ischemia and reperfusion arrhythmia in hearts from type 2 Diabetic Otsuka Long-Evans Tokushima Fatty rats. Cardiovasc Diabetol. 2007;6:17 pubmed
    ..Sensitivity to ischemia and its underlying mechanisms in type 2 diabetic hearts are still largely unknown. Especially, correlation between reperfusion induced ventricular arrhythmia and changes in intracellular pH has not been elucidated...
  75. Luan Y, Hirashima T, Man Z, Wang M, Kawano K, Sumida T. Pathogenesis of obesity by food restriction in OLETF rats-increased intestinal monoacylglycerol acyltransferase activities may be a crucial factor. Diabetes Res Clin Pract. 2002;57:75-82 pubmed
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  77. Sugimoto K, Fujimori A, Yuyama H, Tahara A, Fujimura A. Renal protective effect of YM598, a selective endothelin type A receptor antagonist. J Cardiovasc Pharmacol. 2004;44 Suppl 1:S451-4 pubmed
    ..These data suggest that endothelin is involved in the progression of diabetic nephropathy in OLETF rats, and an endothelin type A antagonist is promising for the treatment of diabetic nephropathy...
  78. Miyasaka K, Nomoto S, Ohta M, Kanai S, Kaneko T, Tahara S, et al. Disturbance of response to acute thermal pain in naturally occurring cholecystokinin-a receptor gene knockout Otsuka Long-Evans Tokushima Fatty (OLETF) rats. J Pharmacol Sci. 2006;101:280-5 pubmed
    ..CCK-AR(-/-) mice did not show any differences from wild-type mice. In conclusion, OLETF rats showed thermal hyperalgesia and disturbed responses to thermal pain, and an alteration of 5-HT function might have a role in this disturbance...
  79. Schroeder M, Lavi Avnon Y, Dagan M, Zagoory Sharon O, Moran T, Weller A. Diurnal and nocturnal nursing behavior in the OLETF rat. Dev Psychobiol. 2007;49:323-33 pubmed
  80. Izumi Y, Ishibashi G, Nakanishi Y, Kikunaga S. Beneficial effect of 3% milled-rice on blood glucose level and serum lipid concentrations in spontaneously non-insulin-dependent diabetic rats. J Nutr Sci Vitaminol (Tokyo). 2007;53:400-9 pubmed
    ..These results indicate that 3% milled-rice has beneficial effects on blood glucose level and serum lipid concentrations in spontaneously non-insulin-dependent diabetic rats...
  81. Miki T, Miura T, Hotta H, Tanno M, Yano T, Sato T, et al. Endoplasmic reticulum stress in diabetic hearts abolishes erythropoietin-induced myocardial protection by impairment of phospho-glycogen synthase kinase-3beta-mediated suppression of mitochondrial permeability transition. Diabetes. 2009;58:2863-72 pubmed publisher
  82. Iwashima Y, Abiko A, Ushikubi F, Hata A, Kaku K, Sano H, et al. Downregulation of the voltage-dependent calcium channel (VDCC) beta-subunit mRNAs in pancreatic islets of type 2 diabetic rats. Biochem Biophys Res Commun. 2001;280:923-32 pubmed
  83. Zhu M, Mizuno A, Noma Y, Murakami T, Kuwajima M, Shima K, et al. Defective morphogenesis and functional maturation in fetal islet-like cell clusters from OLETF rat, a model of NIDDM. Int J Exp Diabetes Res. 2001;1:289-98 pubmed
    ..1mM glucose for 48 to 72-hr and in 5.5mM glucose for 120-hr. Therefore, we concluded that during the fetal stage of islet development, OLETF rats exhibit both morphological and functional defects...
  84. De Jonghe B, Hajnal A, Covasa M. Increased oral and decreased intestinal sensitivity to sucrose in obese, prediabetic CCK-A receptor-deficient OLETF rats. Am J Physiol Regul Integr Comp Physiol. 2005;288:R292-300 pubmed
    ..This enhanced responsiveness to oral stimulation, coupled with the deficit in responding to the postingestive feedback of intestinal sucrose, may contribute additively to the development of hyperphagia and weight gain in OLETF rats...
  85. Kikuchi Y, Imakiire T, Yamada M, Saigusa T, Hyodo T, Hyodo N, et al. Mizoribine reduces renal injury and macrophage infiltration in non-insulin-dependent diabetic rats. Nephrol Dial Transplant. 2005;20:1573-81 pubmed
    ..We examined whether mizoribine, which acts through immunosuppressive mechanisms similar to MMF, inhibits progression of diabetic nephropathy in non-insulin-dependent diabetic rats...
  86. Schroeder M, Zagoory Sharon O, Lavi Avnon Y, Moran T, Weller A. Weight gain and maternal behavior in CCK1 deficient rats. Physiol Behav. 2006;89:402-9 pubmed
    ..Taken together, these data demonstrate that OLETF males and females are heavier from birth and suggest that maternal factors may contribute to weight differences between the strains...
  87. Sakata S, Lebeche D, Sakata Y, Sakata N, Chemaly E, Liang L, et al. Transcoronary gene transfer of SERCA2a increases coronary blood flow and decreases cardiomyocyte size in a type 2 diabetic rat model. Am J Physiol Heart Circ Physiol. 2007;292:H1204-7 pubmed
    ..In conclusion, in DM failing hearts, SERCA2a gene transfer can increase coronary blood flow and reduce cardiomyocyte size without reduction in collagen production...
  88. Ota T, Takamura T, Kurita S, Matsuzawa N, Kita Y, Uno M, et al. Insulin resistance accelerates a dietary rat model of nonalcoholic steatohepatitis. Gastroenterology. 2007;132:282-93 pubmed
    ..The increasing prevalence of nonalcoholic steatohepatitis (NASH) is due to the epidemic of obesity and type 2 diabetes, both of which are associated with insulin resistance...
  89. Nagao K, Higa K, Shirouchi B, Nomura S, Inoue N, Inafuku M, et al. Effect of Vaccinium ashei reade leaves on lipid metabolism in Otsuka Long-Evans Tokushima Fatty rats. Biosci Biotechnol Biochem. 2008;72:1619-22 pubmed
    ..The hypolipidemic effect might be attributable to a reduction of lipogenesis and enhancement of lipolysis in the liver. These results suggest the use of blueberry leaf as a dietary hypolipidemic component...
  90. Moralejo D, Ogino T, Zhu M, Toide K, Wei S, Wei K, et al. Identification of a quantitative trait locus influencing plasma insulin levels after 70% pancreatectomy using the OLETF rat. J Vet Med Sci. 1998;60:1157-60 pubmed
    ..This chromosome 20 QTL, whose OLETF allele is associated with low plasma insulin levels through acting in an incompletely recessive manner, may affect insulin secretion itself rather than beta-cell proliferation...
  91. Ivanov A, Kulchitsky V, Romanovsky A. Does obesity affect febrile responsiveness?. Int J Obes Relat Metab Disord. 2001;25:586-9 pubmed
    ..Since brown fat thermogenesis is also suppressed in obese rodents, we hypothesized that obesity leads to a decreased febrile responsiveness...
  92. Watanobe H, Yoneda M, Kohsaka A, Kakizaki Y, Suda T, Schioth H. Normalization of circulating leptin levels by fasting improves the reproductive function in obese OLETF female rats. Neuropeptides. 2001;35:45-9 pubmed