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Niddm1  -  Non-insulin dependent diabetes mellitus QTL 1

Rattus norvegicus

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Disease relevance of Niddm1


Psychiatry related information on Niddm1


High impact information on Niddm1


Chemical compound and disease context of Niddm1


Biological context of Niddm1


Anatomical context of Niddm1


Associations of Niddm1 with chemical compounds

  • Congenic strains were established for Niddm1, the major quantitative trait locus (QTL) for postprandial glucose levels, by transfer of GK alleles onto the genome of the normoglycemic F344 rat [17].
  • Non-insulin-dependent diabetes (NIDDM) was obtained in adult rats following a neonatal streptozotocin injection [23].
  • Studies were performed to test the hypothesis that impaired insulin action occurs as an acquired phenomenon in the streptozocin (STZ)-treated, non-insulin-dependent (NIDDM) diabetic rat model [24].
  • The onset of NIDDM in obese Zucker diabetic fatty (fa/fa) rats is preceded by a striking increase in the plasma levels of free fatty acids (FFAs) and by a sixfold rise in triglyceride content in the pancreatic islets [25].
  • These results suggested that pioglitazone increased insulin sensitivity in part by activating kinase of the receptors through indirect effect on insulin receptors and that the drug may have useful benefits in insulin resistance of NIDDM [14].

Regulatory relationships of Niddm1


Other interactions of Niddm1


Analytical, diagnostic and therapeutic context of Niddm1

  • We have performed a comprehensive study of the genetic basis of diabetes in the Goto-Kakizaki (GK) rat, the most widely used animal model of non-obese NIDDM [1].
  • The genetic dissection of NIDDM using this model has allowed us to map three independent loci involved in the disease [1].
  • We have examined the effect of chronic (20 days) oral administration of benfluorex (35 mg/kg) in a rat model of NIDDM, induced by injection of STZ 5 days after birth and characterized by frank hyperglycemia, hypoinsulinemia, and hepatic and peripheral insulin resistance [32].
  • The unitary conductance of the channel in diabetic beta-cells was virtually identical to that in control beta cells and there was no difference in the sensitivity to ATP and glibenclamide of KATP channels between the NIDDM and control groups [11].
  • We have used the whole-cell recording technique to determine whether ATP-sensitive potassium (K[ATP]) currents, voltage-dependent Ca2+ currents, and exocytosis are different in single beta-cells from pancreatic islets of Goto-Kakizaki (GK) rats, a novel model of NIDDM, and normal rats [33].


  1. Genetic analysis of non-insulin dependent diabetes mellitus in the GK rat. Galli, J., Li, L.S., Glaser, A., Ostenson, C.G., Jiao, H., Fakhrai-Rad, H., Jacob, H.J., Lander, E.S., Luthman, H. Nat. Genet. (1996) [Pubmed]
  2. Insulin-like growth factor (IGF) gene expression is reduced in neural tissues and liver from rats with non-insulin-dependent diabetes mellitus, and IGF treatment ameliorates diabetic neuropathy. Zhuang, H.X., Wuarin, L., Fei, Z.J., Ishii, D.N. J. Pharmacol. Exp. Ther. (1997) [Pubmed]
  3. Insulin occludes leptin activation of ATP-sensitive K+ channels in rat CRI-G1 insulin secreting cells. Harvey, J., Ashford, M.L. J. Physiol. (Lond.) (1998) [Pubmed]
  4. GLUT-2 function in glucose-unresponsive beta cells of dexamethasone-induced diabetes in rats. Ohneda, M., Johnson, J.H., Inman, L.R., Unger, R.H. J. Clin. Invest. (1993) [Pubmed]
  5. Beta-cell lipotoxicity in the pathogenesis of non-insulin-dependent diabetes mellitus of obese rats: impairment in adipocyte-beta-cell relationships. Lee, Y., Hirose, H., Ohneda, M., Johnson, J.H., McGarry, J.D., Unger, R.H. Proc. Natl. Acad. Sci. U.S.A. (1994) [Pubmed]
  6. Alcohol-related diols cause acute insulin resistance in vivo. Xu, D., Dhillon, A.S., Abelmann, A., Croft, K., Peters, T.J., Palmer, T.N. Metab. Clin. Exp. (1998) [Pubmed]
  7. The glutathione levels are reduced in Goto-Kakizaki rat retina, but are not influenced by aminoguanidine treatment. Agardh, C.D., Agardh, E., Hultberg, B., Qian, Y., Ostenson, C.G. Curr. Eye Res. (1998) [Pubmed]
  8. The role of free radical in the pathogenesis of impotence in streptozotocin-induced diabetic rats. Ryu, J.K., Kim, D.J., Lee, T., Kang, Y.S., Yoon, S.M., Suh, J.K. Yonsei Med. J. (2003) [Pubmed]
  9. Pancreatic beta-cells are rendered glucose-competent by the insulinotropic hormone glucagon-like peptide-1(7-37). Holz, G.G., Kühtreiber, W.M., Habener, J.F. Nature (1993) [Pubmed]
  10. Reduced tyrosine kinase activity of the insulin receptor in obesity-diabetes. Central role of tumor necrosis factor-alpha. Hotamisligil, G.S., Budavari, A., Murray, D., Spiegelman, B.M. J. Clin. Invest. (1994) [Pubmed]
  11. Impaired glucose sensitivity of ATP-sensitive K+ channels in pancreatic beta-cells in streptozotocin-induced NIDDM rats. Tsuura, Y., Ishida, H., Okamoto, Y., Tsuji, K., Kurose, T., Horie, M., Imura, H., Okada, Y., Seino, Y. Diabetes (1992) [Pubmed]
  12. In vivo hepatic and peripheral insulin sensitivity in rats with non-insulin-dependent diabetes induced by streptozocin. Assessment with the insulin-glucose clamp technique. Kergoat, M., Portha, B. Diabetes (1985) [Pubmed]
  13. Troglitazone prevents hyperglycemia-induced but not glucosamine-induced insulin resistance. Miles, P.D., Higo, K., Romeo, O.M., Lee, M.K., Rafaat, K., Olefsky, J.M. Diabetes (1998) [Pubmed]
  14. Pioglitazone increases insulin sensitivity by activating insulin receptor kinase. Kobayashi, M., Iwanishi, M., Egawa, K., Shigeta, Y. Diabetes (1992) [Pubmed]
  15. Abnormal insulin secretion in a streptozocin model of diabetes. Effects of insulin treatment. Leahy, J.L., Bonner-Weir, S., Weir, G.C. Diabetes (1985) [Pubmed]
  16. Insulin-degrading enzyme identified as a candidate diabetes susceptibility gene in GK rats. Fakhrai-Rad, H., Nikoshkov, A., Kamel, A., Fernström, M., Zierath, J.R., Norgren, S., Luthman, H., Galli, J. Hum. Mol. Genet. (2000) [Pubmed]
  17. Pathophysiological and genetic characterization of the major diabetes locus in GK rats. Galli, J., Fakhrai-Rad, H., Kamel, A., Marcus, C., Norgren, S., Luthman, H. Diabetes (1999) [Pubmed]
  18. Phenotyping of individual pancreatic islets locates genetic defects in stimulus secretion coupling to Niddm1i within the major diabetes locus in GK rats. Lin, J.M., Ortsäter, H., Fakhrai-Rad, H., Galli, J., Luthman, H., Bergsten, P. Diabetes (2001) [Pubmed]
  19. Enhanced expression of hepatic acyl-coenzyme A synthetase and microsomal triglyceride transfer protein messenger RNAs in the obese and hypertriglyceridemic rat with visceral fat accumulation. Kuriyama, H., Yamashita, S., Shimomura, I., Funahashi, T., Ishigami, M., Aragane, K., Miyaoka, K., Nakamura, T., Takemura, K., Man, Z., Toide, K., Nakayama, N., Fukuda, Y., Lin, M.C., Wetterau, J.R., Matsuzawa, Y. Hepatology (1998) [Pubmed]
  20. Insulin production and glucose metabolism in isolated pancreatic islets of rats with NIDDM. Portha, B., Giroix, M.H., Serradas, P., Welsh, N., Hellerström, C., Sener, A., Malaisse, W.J. Diabetes (1988) [Pubmed]
  21. Effect of insulin on glucose utilization in epitrochlearis muscle of rats with streptozocin-induced NIDDM. Karl, I.E., Gavin, J.R., Levy, J. Diabetes (1990) [Pubmed]
  22. Abnormalities of insulin responses after ambient and previous exposure to glucose in streptozocin-diabetic and dexamethasone-treated rats. Role of hyperglycemia and increased B-cell demands. Grill, V., Rundfeldt, M. Diabetes (1986) [Pubmed]
  23. Glucose insensitivity and amino-acid hypersensitivity of insulin release in rats with non-insulin-dependent diabetes. A study with the perfused pancreas. Giroix, M.H., Portha, B., Kergoat, M., Bailbe, D., Picon, L. Diabetes (1983) [Pubmed]
  24. Impaired insulin action in rats with non-insulin-dependent diabetes. Levy, J., Gavin, J.R., Fausto, A., Gingerich, R.L., Avioli, L.V. Diabetes (1984) [Pubmed]
  25. Increased lipogenic capacity of the islets of obese rats: a role in the pathogenesis of NIDDM. Lee, Y., Hirose, H., Zhou, Y.T., Esser, V., McGarry, J.D., Unger, R.H. Diabetes (1997) [Pubmed]
  26. Plasma glucagon responses to insulin-induced hypoglycemia and arginine in spontaneous non-insulin-dependent diabetes mellitus (NIDDM) rats, Otsuka Long Evans Tokushima Fatty (OLETF) strain. Ishida, K., Mizuno, A., Sano, T., Shi, K., Shima, K. Acta Endocrinol. (1993) [Pubmed]
  27. Uncoupling protein-3 mRNA levels are increased in white adipose tissue and skeletal muscle of bezafibrate-treated rats. Cabrero, A., Llaverías, G., Roglans, N., Alegret, M., Sánchez, R., Adzet, T., Laguna, J.C., Vázquez, M. Biochem. Biophys. Res. Commun. (1999) [Pubmed]
  28. Alterations in insulin-induced postreceptor signaling in adipocytes of the Otsuka Long-Evans Tokushima fatty rat strain. Ishizuka, T., Miura, A., Kajita, K., Yamada, K., Wada, H., Itaya, S., Kanoh, Y., Ishizawa, M., Kimura, M., Yasuda, K. J. Endocrinol. (1998) [Pubmed]
  29. Effects of pioglitazone on promoting energy storage, not expenditure, in brown adipose tissue of obese fa/fa Zucker rats: comparison to CL 316,243. Burkey, B.F., Dong, M., Gagen, K., Eckhardt, M., Dragonas, N., Chen, W., Grosenstein, P., Argentieri, G., de Souza, C.J. Metab. Clin. Exp. (2000) [Pubmed]
  30. Evidence of cosecretion of islet amyloid polypeptide and insulin by beta-cells. Kahn, S.E., D'Alessio, D.A., Schwartz, M.W., Fujimoto, W.Y., Ensinck, J.W., Taborsky, G.J., Porte, D. Diabetes (1990) [Pubmed]
  31. TNF-alpha-induced insulin resistance in vivo and its prevention by troglitazone. Miles, P.D., Romeo, O.M., Higo, K., Cohen, A., Rafaat, K., Olefsky, J.M. Diabetes (1997) [Pubmed]
  32. Benfluorex normalizes hyperglycemia and reverses hepatic insulin resistance in STZ-induced diabetic rats. Serradas, P., Blondel, O., Bailbe, D., Portha, B. Diabetes (1993) [Pubmed]
  33. Electrophysiological and metabolic characterization of single beta-cells and islets from diabetic GK rats. Hughes, S.J., Faehling, M., Thorneley, C.W., Proks, P., Ashcroft, F.M., Smith, P.A. Diabetes (1998) [Pubmed]
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