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Gene Review

NIDDM1  -  non-insulin-dependent diabetes mellitus...

Homo sapiens

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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

  • Whereas the first three subgroups did not differ among themselves, they had significantly lower glucose utilization than did the normotensive NIDDM1 patients without microalbuminuria and nondiabetic controls (P < 0.01) [27].
  • Seventy-five NIDDM patients attending the outpatient clinic of the Department of Internal Medicine of the University Hospital in Padua, Italy participated in the cross-sectional part of our study [3].
  • These preliminary results suggest that partial replacement of complex carbohydrates with monounsaturated fatty acids in the diets of patients with NIDDM does not increase the level of LDL cholesterol and may improve glycemic control and the levels of plasma triglycerides and HDL cholesterol [28].
  • CONCLUSIONS: Metformin monotherapy and combination therapy with metformin and sulfonylurea are well tolerated and improve glycemic control and lipid concentrations in patients with NIDDM whose diabetes is poorly controlled with diet or sulfonylurea therapy alone [29].
  • Association studies were performed in 642 Pima subjects (390 with NIDDM and 252 without NIDDM) [24].

Physical interactions of NIDDM1


Regulatory relationships of NIDDM1

  • The frequency of the inactive ALDH2 genotype was higher than that in the normal control subjects (P < 0.002) and that in the NIDDM control subjects (P < 0.003) [33].
  • In contrast, platelet surface expression of CD36 in NIDDM (6.5 +/- 0.56 pmol/mg protein) was not significantly different from those of normal controls despite higher total content of CD36 (32.8 +/- 1.2, pmol/mg protein, p < 0 .01) [34].
  • In response to 40 mU insulin, HKII mRNA in lean control subjects was increased 1.48 +/- 0.18-fold (P < 0.05) but failed to increase significantly in the obese (1.12 +/- 0.24) or NIDDM (1.14 +/- 0.18) groups [35].
  • CONCLUSIONS: Gliclazide administration to NIDDM patients inhibits the increased adhesiveness of diabetic monocytes to endothelial cells and reduces the production of TNF-alpha by these cells [36].
  • We conclude that 1. acute elevation of glucose by 5.5 mmol/L or more can activate PKC beta 2 translocation in controls and NIDDM patients in vivo irrespective of parameters of metabolic control [37].

Other interactions of NIDDM1

  • These subjects were divided into four groups on the basis of BP levels and albumin excretion rate (AER): 28 normotensive normoalbuminuric (NIDDM1), 19 hypertensive normoalbuminuric (NIDDM2), 15 normotensive microalbuminuric (NIDDM3), and 13 hypertensive microalbuminuric patients (NIDDM4) [3].
  • We found some evidence for linkage of T2DM to chromosome 2q approximately 20 cM proximal to the NIDDM1/CAPN10 locus [38].
  • A recent random genome mapping study has localized a locus termed NIDDM2 that maps to the region of chromosome 12 that includes MODY3, one of the three genes responsible for maturity-onset diabetes of the young, a monogenic form of NIDDM characterized by early age of onset and autosomal dominant inheritance [21].
  • Genetic variation in the hepatocyte nuclear factor-1 alpha gene in Danish Caucasians with late-onset NIDDM [21].
  • None of the polymorphism carriers had both aminoacid variants and the total allelic frequency of IRS-1 polymorphisms was about three times higher in patients with NIDDM than in controls (p = 0.02) [39].

Analytical, diagnostic and therapeutic context of NIDDM1


  1. Genetic variation in the gene encoding calpain-10 is associated with type 2 diabetes mellitus. Horikawa, Y., Oda, N., Cox, N.J., Li, X., Orho-Melander, M., Hara, M., Hinokio, Y., Lindner, T.H., Mashima, H., Schwarz, P.E., del Bosque-Plata, L., Horikawa, Y., Oda, Y., Yoshiuchi, I., Colilla, S., Polonsky, K.S., Wei, S., Concannon, P., Iwasaki, N., Schulze, J., Baier, L.J., Bogardus, C., Groop, L., Boerwinkle, E., Hanis, C.L., Bell, G.I. Nat. Genet. (2000) [Pubmed]
  2. A genome-wide search for human non-insulin-dependent (type 2) diabetes genes reveals a major susceptibility locus on chromosome 2. Hanis, C.L., Boerwinkle, E., Chakraborty, R., Ellsworth, D.L., Concannon, P., Stirling, B., Morrison, V.A., Wapelhorst, B., Spielman, R.S., Gogolin-Ewens, K.J., Shepard, J.M., Williams, S.R., Risch, N., Hinds, D., Iwasaki, N., Ogata, M., Omori, Y., Petzold, C., Rietzch, H., Schröder, H.E., Schulze, J., Cox, N.J., Menzel, S., Boriraj, V.V., Chen, X., Lim, L.R., Lindner, T., Mereu, L.E., Wang, Y.Q., Xiang, K., Yamagata, K., Yang, Y., Bell, G.I. Nat. Genet. (1996) [Pubmed]
  3. Impaired insulin-induced glucose uptake by extrahepatic tissue is hallmark of NIDDM patients who have or will develop hypertension and microalbuminuria. Nosadini, R., Solini, A., Velussi, M., Muollo, B., Frigato, F., Sambataro, M., Cipollina, M.R., De Riva, F., Brocco, E., Crepaldi, G. Diabetes (1994) [Pubmed]
  4. Quantitative trait linkage analysis of lipid-related traits in familial type 2 diabetes: evidence for linkage of triglyceride levels to chromosome 19q. Elbein, S.C., Hasstedt, S.J. Diabetes (2002) [Pubmed]
  5. No evidence for involvement of the calpain-10 gene 'high-risk' haplotype combination for non-insulin-dependent diabetes mellitus in early onset obesity. Hinney, A., Antwerpen, B., Geller, F., Schäfer, H., Siegfried, W., Goldschmidt, H., Remschmidt, H., Ziegler, A., Hebebrand, J. Mol. Genet. Metab. (2002) [Pubmed]
  6. Physical activity and reduced occurrence of non-insulin-dependent diabetes mellitus. Helmrich, S.P., Ragland, D.R., Leung, R.W., Paffenbarger, R.S. N. Engl. J. Med. (1991) [Pubmed]
  7. Differences in 4-year health outcomes for elderly and poor, chronically ill patients treated in HMO and fee-for-service systems. Results from the Medical Outcomes Study. Ware, J.E., Bayliss, M.S., Rogers, W.H., Kosinski, M., Tarlov, A.R. JAMA (1996) [Pubmed]
  8. The genetic analysis of multiple sclerosis. Sawcer, S., Goodfellow, P.N., Compston, A. Trends Genet. (1997) [Pubmed]
  9. Archaeology of NIDDM. Excavation of the "thrifty" genotype. Wendorf, M., Goldfine, I.D. Diabetes (1991) [Pubmed]
  10. Preventing non-insulin-dependent diabetes. Knowler, W.C., Narayan, K.M., Hanson, R.L., Nelson, R.G., Bennett, P.H., Tuomilehto, J., Scherstén, B., Pettitt, D.J. Diabetes (1995) [Pubmed]
  11. Metabolic coupling factors in pancreatic beta-cell signal transduction. Newgard, C.B., McGarry, J.D. Annu. Rev. Biochem. (1995) [Pubmed]
  12. Pathophysiology of insulin resistance in human disease. Reaven, G.M. Physiol. Rev. (1995) [Pubmed]
  13. Loci on chromosomes 2 (NIDDM1) and 15 interact to increase susceptibility to diabetes in Mexican Americans. Cox, N.J., Frigge, M., Nicolae, D.L., Concannon, P., Hanis, C.L., Bell, G.I., Kong, A. Nat. Genet. (1999) [Pubmed]
  14. Lovastatin for lowering cholesterol levels in non-insulin-dependent diabetes mellitus. Garg, A., Grundy, S.M. N. Engl. J. Med. (1988) [Pubmed]
  15. Metabolic effects of metformin in non-insulin-dependent diabetes mellitus. Stumvoll, M., Nurjhan, N., Perriello, G., Dailey, G., Gerich, J.E. N. Engl. J. Med. (1995) [Pubmed]
  16. Hyperinsulinemia in a population at high risk for non-insulin-dependent diabetes mellitus. Haffner, S.M., Stern, M.P., Hazuda, H.P., Pugh, J.A., Patterson, J.K. N. Engl. J. Med. (1986) [Pubmed]
  17. Improvement in glucose tolerance and insulin resistance in obese subjects treated with troglitazone. Nolan, J.J., Ludvik, B., Beerdsen, P., Joyce, M., Olefsky, J. N. Engl. J. Med. (1994) [Pubmed]
  18. Population genetics of CAPN10 and GPR35: implications for the evolution of type 2 diabetes variants. Vander Molen, J., Frisse, L.M., Fullerton, S.M., Qian, Y., Del Bosque-Plata, L., Hudson, R.R., Di Rienzo, A. Am. J. Hum. Genet. (2005) [Pubmed]
  19. Variants within the calpain-10 gene on chromosome 2q37 (NIDDM1) and relationships to type 2 diabetes, insulin resistance, and impaired acute insulin secretion among Scandinavian Caucasians. Rasmussen, S.K., Urhammer, S.A., Berglund, L., Jensen, J.N., Hansen, L., Echwald, S.M., Borch-Johnsen, K., Horikawa, Y., Mashima, H., Lithell, H., Cox, N.J., Hansen, T., Bell, G.I., Pedersen, O. Diabetes (2002) [Pubmed]
  20. A large sample of finnish diabetic sib-pairs reveals no evidence for a non-insulin-dependent diabetes mellitus susceptibility locus at 2qter. Ghosh, S., Hauser, E.R., Magnuson, V.L., Valle, T., Ally, D.S., Karanjawala, Z.E., Rayman, J.B., Knapp, J.I., Musick, A., Tannenbaum, J., Te, C., Eldridge, W., Shapiro, S., Musick, T., Martin, C., So, A., Witt, A., Harvan, J.B., Watanabe, R.M., Hagopian, W., Eriksson, J., Nylund, S.J., Kohtamaki, K., Tuomilehto-Wolf, E., Boehnke, M. J. Clin. Invest. (1998) [Pubmed]
  21. Genetic variation in the hepatocyte nuclear factor-1 alpha gene in Danish Caucasians with late-onset NIDDM. Urhammer, S.A., Rasmussen, S.K., Kaisaki, P.J., Oda, N., Yamagata, K., Møller, A.M., Fridberg, M., Hansen, L., Hansen, T., Bell, G.I., Pedersen, O. Diabetologia (1997) [Pubmed]
  22. Association between polymorphism of the glycogen synthase gene and non-insulin-dependent diabetes mellitus. Groop, L.C., Kankuri, M., Schalin-Jäntti, C., Ekstrand, A., Nikula-Ijäs, P., Widén, E., Kuismanen, E., Eriksson, J., Franssila-Kallunki, A., Saloranta, C. N. Engl. J. Med. (1993) [Pubmed]
  23. Role of reduced suppression of glucose production and diminished early insulin release in impaired glucose tolerance. Mitrakou, A., Kelley, D., Mokan, M., Veneman, T., Pangburn, T., Reilly, J., Gerich, J. N. Engl. J. Med. (1992) [Pubmed]
  24. Time of onset of non-insulin-dependent diabetes mellitus and genetic variation in the beta 3-adrenergic-receptor gene. Walston, J., Silver, K., Bogardus, C., Knowler, W.C., Celi, F.S., Austin, S., Manning, B., Strosberg, A.D., Stern, M.P., Raben, N. N. Engl. J. Med. (1995) [Pubmed]
  25. Mutations in the hepatocyte nuclear factor-1alpha gene in maturity-onset diabetes of the young (MODY3). Yamagata, K., Oda, N., Kaisaki, P.J., Menzel, S., Furuta, H., Vaxillaire, M., Southam, L., Cox, R.D., Lathrop, G.M., Boriraj, V.V., Chen, X., Cox, N.J., Oda, Y., Yano, H., Le Beau, M.M., Yamada, S., Nishigori, H., Takeda, J., Fajans, S.S., Hattersley, A.T., Iwasaki, N., Hansen, T., Pedersen, O., Polonsky, K.S., Bell, G.I. Nature (1996) [Pubmed]
  26. Long-term effect of insulin on glucose transport and insulin binding in cultured adipocytes from normal and obese humans with and without non-insulin-dependent diabetes. Sinha, M.K., Taylor, L.G., Pories, W.J., Flickinger, E.G., Meelheim, D., Atkinson, S., Sehgal, N.S., Caro, J.F. J. Clin. Invest. (1987) [Pubmed]
  27. Close relationship between microalbuminuria and insulin resistance in essential hypertension and non-insulin dependent diabetes mellitus. Nosadini, R., Cipollina, M.R., Solini, A., Sambataro, M., Morocutti, A., Doria, A., Fioretto, P., Brocco, E., Muollo, B., Frigato, F. J. Am. Soc. Nephrol. (1992) [Pubmed]
  28. Comparison of a high-carbohydrate diet with a high-monounsaturated-fat diet in patients with non-insulin-dependent diabetes mellitus. Garg, A., Bonanome, A., Grundy, S.M., Zhang, Z.J., Unger, R.H. N. Engl. J. Med. (1988) [Pubmed]
  29. Efficacy of metformin in patients with non-insulin-dependent diabetes mellitus. The Multicenter Metformin Study Group. DeFronzo, R.A., Goodman, A.M. N. Engl. J. Med. (1995) [Pubmed]
  30. Decreased muscle glucose transport/phosphorylation is an early defect in the pathogenesis of non-insulin-dependent diabetes mellitus. Rothman, D.L., Magnusson, I., Cline, G., Gerard, D., Kahn, C.R., Shulman, R.G., Shulman, G.I. Proc. Natl. Acad. Sci. U.S.A. (1995) [Pubmed]
  31. Stimulation of glucose uptake by insulin-like growth factor II in human muscle is not mediated by the insulin-like growth factor II/mannose 6-phosphate receptor. Burguera, B., Elton, C.W., Caro, J.F., Tapscott, E.B., Pories, W.J., Dimarchi, R., Sakano, K., Dohm, G.L. Biochem. J. (1994) [Pubmed]
  32. Epistatic effects of genes encoding tumor necrosis factor-alpha, immunoglobulin allotypes, and HLA antigens on susceptibility to non-insulin-dependent (type 2) diabetes mellitus. Pandey, J.P., Zamani, M., Cassiman, J.J. Immunogenetics (1999) [Pubmed]
  33. Mitochondrial aldehyde dehydrogenase in diabetes associated with mitochondrial tRNA(Leu(UUR)) mutation at position 3243. Suzuki, Y., Muramatsu, T., Taniyama, M., Atsumi, Y., Suematsu, M., Kawaguchi, R., Higuchi, S., Asahina, T., Murata, C., Handa, M., Matsuoka, K. Diabetes Care (1996) [Pubmed]
  34. Surface expression of fatty acid translocase (FAT/CD36) on platelets in myeloproliferative disorders and non-insulin dependent diabetes mellitus: effect on arachidonic acid uptake. Salah-Uddin, H., Gordon, M.J., Ford, I., Tandon, N.N., Greaves, M., Duttaroy, A.K. Mol. Cell. Biochem. (2002) [Pubmed]
  35. Insulin-induced hexokinase II expression is reduced in obesity and NIDDM. Pendergrass, M., Koval, J., Vogt, C., Yki-Jarvinen, H., Iozzo, P., Pipek, R., Ardehali, H., Printz, R., Granner, D., DeFronzo, R.A., Mandarino, L.J. Diabetes (1998) [Pubmed]
  36. Normalization of plasma lipid peroxides, monocyte adhesion, and tumor necrosis factor-alpha production in NIDDM patients after gliclazide treatment. Desfaits, A.C., Serri, O., Renier, G. Diabetes Care (1998) [Pubmed]
  37. Activation of human platelet protein kinase C-beta 2 in vivo in response to acute hyperglycemia. Pirags, V., Assert, R., Haupt, K., Schatz, H., Pfeiffer, A. Exp. Clin. Endocrinol. Diabetes (1996) [Pubmed]
  38. Role of calpain-10 gene variants in familial type 2 diabetes in Caucasians. Elbein, S.C., Chu, W., Ren, Q., Hemphill, C., Schay, J., Cox, N.J., Hanis, C.L., Hasstedt, S.J. J. Clin. Endocrinol. Metab. (2002) [Pubmed]
  39. Aminoacid polymorphisms of insulin receptor substrate-1 in non-insulin-dependent diabetes mellitus. Almind, K., Bjørbaek, C., Vestergaard, H., Hansen, T., Echwald, S., Pedersen, O. Lancet (1993) [Pubmed]
  40. Early metabolic defects in persons at increased risk for non-insulin-dependent diabetes mellitus. Eriksson, J., Franssila-Kallunki, A., Ekstrand, A., Saloranta, C., Widén, E., Schalin, C., Groop, L. N. Engl. J. Med. (1989) [Pubmed]
  41. Comparison of insulin regimens in patients with non-insulin-dependent diabetes mellitus. Yki-Järvinen, H., Kauppila, M., Kujansuu, E., Lahti, J., Marjanen, T., Niskanen, L., Rajala, S., Ryysy, L., Salo, S., Seppälä, P. N. Engl. J. Med. (1992) [Pubmed]
  42. Chromosomal mapping of genetic loci associated with non-insulin dependent diabetes in the GK rat. Gauguier, D., Froguel, P., Parent, V., Bernard, C., Bihoreau, M.T., Portha, B., James, M.R., Penicaud, L., Lathrop, M., Ktorza, A. Nat. Genet. (1996) [Pubmed]
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