Insulin receptor substrate 2 plays a crucial role in β cells and the hypothalamus
Open accessAbstract
We previously demonstrated that insulin receptor substrate 2 (Irs2) KO mice develop diabetes associated with hepatic insulin resistance, lack of compensatory beta cell hyperplasia, and leptin resistance. To more precisely determine the roles of Irs2 in beta cells and the hypothalamus, we generated beta cell-specific Irs2 KO and hypothalamus-specific Irs2 knockdown (betaHT-IRS2) mice. Expression of Irs2 mRNA was reduced by approximately 90% in pancreatic islets and was markedly reduced in the arcuate nucleus of the hypothalamus. By contrast, Irs2 expression in liver, muscle, and adipose tissue of betaHT-IRS2 mice was indistinguishable from that of control mice. The betaHT-IRS2 mice displayed obesity and leptin resistance. At 4 weeks of age, the betaHT-IRS2 mice showed normal insulin sensitivity, but at 8 and 12 weeks, they were insulin resistant with progressive obesity. Despite their normal insulin sensitivity at 8 weeks with caloric restriction, the betaHT-IRS2 mice exhibited glucose intolerance and impaired glucose-induced insulin secretion. beta Cell mass and beta cell proliferation in the betaHT-IRS2 mice were reduced significantly at 8 and 12 weeks but not at 10 days. Insulin secretion, normalized by cell number per islet, was significantly increased at high glucose concentrations in the betaHT-IRS2 mice. We conclude that, in beta cells and the hypothalamus, Irs2 is crucially involved in the regulation of beta cell mass and leptin sensitivity.
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Neuron-specific deletion of either insulin receptor or IRS-2 in mice causes mild obesity and insulin resistance.
“mice with neuron-specific deletion of either the insulin receptor (IR) or insulin receptor-substrate-2 (IRS-2) are characterized by mild obesity and insulin resistance (27, 97, 105).”
From Leptin and the Central Nervous System Control of Glucose Metabolism (2011) · cites this paper as [97]
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REGIONAL STUDIES OF CATECHOLAMINES IN THE RAT BRAIN‐I
Glowinski, J., & Iversen, L. L. (1966) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.1966.tb09873.x · Cited by 5,436 · see citing works
Insulin signalling and the regulation of glucose and lipid metabolism
Saltiel, A. R., & Kahn, C. R. (2001) · Nature · doi:10.1038/414799a · Cited by 5,326 · see citing works
Cellular mechanisms of insulin resistance
Shulman, G. I. (2000) · Journal of Clinical Investigation · doi:10.1172/jci10583 · Cited by 2,714 · see citing works
Role of Brain Insulin Receptor in Control of Body Weight and Reproduction
Brüning, J. C., Gautam, D., Burks, D. J., Gillette, J., Schubert, M., Orban, P. C., Klein, R., Krone, W., Müller-Wieland, D., & Kahn, C. R. (2000) · Science · doi:10.1126/science.289.5487.2122 · Cited by 2,235 · see citing works
Disruption of IRS-2 causes type 2 diabetes in mice
Withers, D., Gutiérrez, J., Towery, H., Burks, D., Ren, J.-M., Previs, S., Zhang, Y., Bernal, D., Pons, S., Shulman, G., et al. (1998) · Nature · doi:10.1038/36116 · Cited by 1,850 · see citing works
PDX-1 is required for pancreatic outgrowth and differentiation of the rostral duodenum
Offield, M. F., Jetton, T. L., Labosky, P. A., Ray, M., Stein, R. W., Magnuson, M. A., Hogan, B. L. M., & Wright, C. V. E. (1996) · Development · doi:10.1242/dev.122.3.983 · Cited by 1,514 · see citing works
PPARγ Mediates High-Fat Diet–Induced Adipocyte Hypertrophy and Insulin Resistance
Kubota, N., Terauchi, Y., Miki, H., Tamemoto, H., Yamauchi, T., Komeda, K., Satoh, S., Nakano, R., Ishii, C., 杉山, 拓., et al. (1999) · Molecular Cell · doi:10.1016/s1097-2765(00)80210-5 · Cited by 1,342 · see citing works
Self-citationAlternative pathway of insulin signalling in mice with targeted disruption of the IRS-1 gene
Araki, E., Lipes, M. A., Patti, M.-E., Brüning, J. C., Haag III, B., Johnson, R. S., & Kahn, C. R. (1994) · Nature · doi:10.1038/372186a0 · Cited by 1,252 · see citing works
Disruption of Adiponectin Causes Insulin Resistance and Neointimal Formation
Kubota, N., Terauchi, Y., Yamauchi, T., Kubota, T., Moroi, M., Matsui, J., Eto, K., Yamashita, T., Kamon, J., Satoh, H., et al. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.c200251200 · Cited by 1,213 · see citing works
Self-citationKulkarni, R., Brüning, J. C., Winnay, J. N., Postic, C., Magnuson, M. A., & Kahn, C. R. (1999) · Cell · doi:10.1016/s0092-8674(00)80546-2 · Cited by 1,148 · see citing works
Disruption of adiponectin causes insulin resistance and neointimal formation
Froguel, P. (2002) · HAL · Cited by 1,126 · see citing works
Insulin resistance and growth retardation in mice lacking insulin receptor substrate-1
Tamemoto, H., Kadowaki, T., Tobe, K., Yagi, T., Sakura, H., Hayakawa, T., Terauchi, Y., Ueki, K., Kaburagi, Y., Satoh, S., et al. (1994) · Nature · doi:10.1038/372182a0 · Cited by 1,082 · see citing works
Self-citationProtein–protein interaction in insulin signaling and the molecular mechanisms of insulin resistance
Virkamäki, A., Ueki, K., & Kahn, C. R. (1999) · Journal of Clinical Investigation · doi:10.1172/jci6609 · Cited by 854 · see citing works
Self-citationThe IRS-signalling system: A network of docking proteins that mediate insulin action
White, M. F. (1998) · Springer eBooks · doi:10.1007/978-1-4615-5647-3_1 · Cited by 673 · see citing works
Distinct and Overlapping Functions of Insulin and IGF-I Receptors
Nakae, J., Kido, Y., & Accili, D. (2001) · Endocrine Reviews · doi:10.1210/edrv.22.6.0452 · Cited by 556 · see citing works
Kubota, N., Tobe, K., Terauchi, Y., Eto, K., Yamauchi, T., Suzuki, R., Tsubamoto, Y., Komeda, K., Nakano, R., Miki, H., et al. (2000) · Diabetes · doi:10.2337/diabetes.49.11.1880 · Cited by 550 · see citing works
Self-citationThe IRS-signalling system: A network of docking proteins that mediate insulin action
White, M. F. (1998) · Molecular and Cellular Biochemistry · doi:10.1023/a:1006806722619 · Cited by 534 · see citing works
Irs-2 coordinates Igf-1 receptor-mediated β-cell development and peripheral insulin signalling
Withers, D. J., Burks, D. J., Towery, H. H., Altamuro, S. L., Flint, C. L., & White, M. F. (1999) · Nature Genetics · doi:10.1038/12631 · Cited by 530 · see citing works
Kulkarni, R. N., Holzenberger, M., Shih, D. Q., Özcan, U., Stoffel, M., Magnuson, M. A., & Kahn, C. R. (2002) · Nature Genetics · doi:10.1038/ng872 · Cited by 363 · see citing works
Kulkarni, R. N., Wang, Z. L., Wang, R. M., Hurley, J. D., Smith, D. M., Ghatei, M. A., Withers, D. J., Gardiner, J. V., Bailey, C. J., & Bloom, S. R. (1997) · Journal of Clinical Investigation · doi:10.1172/jci119818 · Cited by 296 · see citing works
Altered function of insulin receptor substrate-1–deficient mouse islets and cultured β-cell lines
Kulkarni, R., Winnay, J. N., Daniels, M. S., Brüning, J. C., Flier, S. N., Hanahan, D., & Kahn, C. R. (1999) · Journal of Clinical Investigation · doi:10.1172/jci8339 · Cited by 266 · see citing works
Insights into insulin resistance and type 2 diabetes from knockout mouse models
Kadowaki, T. (2000) · Journal of Clinical Investigation · doi:10.1172/jci10830 · Cited by 252 · see citing works
Self-citationInsulin-stimulated Insulin Secretion in Single Pancreatic Beta Cells
Aspinwall, C. A., Lakey, J. R. T., & Kennedy, R. T. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.10.6360 · Cited by 216 · see citing works
Pdx1 restores β cell function in Irs2 knockout mice
Kushner, J. A., Ye, J., Schubert, M., Burks, D. J., Dow, M. A., Flint, C. L., Dutta, S., Wright, C. V. E., Montminy, M., & White, M. F. (2002) · Journal of Clinical Investigation · doi:10.1172/jci14439 · Cited by 176 · see citing works
The Gly972→Arg amino acid polymorphism in IRS-1 impairs insulin secretion in pancreatic β cells
Porzio, O., Federici, M., Hribal, M. L., Lauro, D., Accili, D., Lauro, R., Borboni, P., & Sesti, G. (1999) · Journal of Clinical Investigation · doi:10.1172/jci5870 · Cited by 154 · see citing works
Pdx1 restores β cell function in Irs2 knockout mice
Kushner, J. A., Ye, J., Schubert, M., Burks, D. J., Dow, M. A., Flint, C. L., Dutta, S., Wright, C. V. E., Montminy, M., & White, M. F. (2002) · Journal of Clinical Investigation · doi:10.1172/jci0214439 · Cited by 151 · see citing works
Terauchi, Y., Iwamoto, K., Tamemoto, H., Komeda, K., Ishii, C., Kanazawa, Y., Asanuma, N., Aizawa, T., Akanuma, Y., Yasuda, K., et al. (1997) · Journal of Clinical Investigation · doi:10.1172/jci119250 · Cited by 145 · see citing works
Self-citationEssential Role of STAT3 in Body Weight and Glucose Homeostasis
Cui, Y., Huang, L., Elefteriou, F., Yang, G., Shelton, J. M., Giles, J. E., Öz, O. K., Pourbahrami, T., Lu, C. Y., Richardson, J. A., et al. (2003) · Molecular and Cellular Biology · doi:10.1128/mcb.24.1.258-269.2004 · Cited by 142 · see citing works
Tobe, K., Suzuki, R., Aoyama, M., Yamauchi, T., Kamon, J., Kubota, N., Terauchi, Y., Matsui, J., Akanuma, Y., Kimura, S., et al. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.c100160200 · Cited by 132 · see citing works
Self-citationHypothalamic nitric oxide synthase gene expression is regulated by thyroid hormones
Ueta, Y., Levy, A., Chowdrey, H. S., & Lightman, S. L. (1995) · Endocrinology · doi:10.1210/endo.136.10.7545100 · Cited by 109 · see citing works
Self-citationTaniguchi, M., Sanbo, M., Watanabe, S., Naruse, I., Mishina, M., & Yagi, T. (1998) · Nucleic Acids Research · doi:10.1093/nar/26.2.679 · Cited by 101 · see citing works
Knockout models are useful tools to dissect the pathophysiology and genetics of insulin resistance
Mauvais‐Jarvis, F., Kulkarni, R., & Kahn, C. R. (2002) · Clinical Endocrinology · doi:10.1046/j.1365-2265.2002.01563.x · Cited by 82 · see citing works
Eto, K., Yamashita, T., Tsubamoto, Y., Terauchi, Y., Hirose, K., Kubota, N., Yamashita, S., Taka, J., Satoh, S., Sekihara, H., et al. (2002) · Diabetes · doi:10.2337/diabetes.51.1.87 · Cited by 72 · see citing works
Self-citationSuzuki, R., Tobe, K., Aoyama, M., Inoue, A., Sakamoto, K. Q., Yamauchi, T., Kamon, J., Kubota, N., Terauchi, Y., Yoshimatsu, H., et al. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m311956200 · Cited by 59 · see citing works
Self-citationA kinase in the life of the β cell
Accili, D. (2001) · Journal of Clinical Investigation · doi:10.1172/jci14454 · Cited by 48 · see citing works
Ohtsuka, N., Urase, K., Momoi, T., & Nogawa, H. (2001) · Developmental Dynamics · doi:10.1002/dvdy.1206 · Cited by 36 · see citing works
Ueta, Y., Levy, A., Chowdrey, H. S., & Lightman, S. L. (1995) · Journal of Neuroendocrinology · doi:10.1111/j.1365-2826.1995.tb00783.x · Cited by 31 · see citing works
Self-citationTerauchi, Y., Matsui, J., Suzuki, R., Kubota, N., Komeda, K., Aizawa, S., Eto, K., Kimura, S., Nagai, R., Tobe, K., et al. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m211045200 · Cited by 29 · see citing works
Self-citationPdx1 Expression in Irs2-deficient Mouse β-Cells Is Regulated in a Strain-dependent Manner
Suzuki, R., Tobe, K., Terauchi, Y., Komeda, K., Kubota, N., Eto, K., Yamauchi, T., Azuma, K., Kaneto, H., Taguchi, T., et al. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m307004200 · Cited by 28 · see citing works
Self-citationPdx1 restores β cell function in Irs2 knockout mice
Kushner, J. A., Ye, J., Schubert, M., Burks, D. J., Dow, M. A., Flint, C. L., Dutta, S., Wright, C. V. E., Montminy, M., & White, M. F. (2002) · Journal of Clinical Investigation · doi:10.1172/jci200214439 · Cited by 9 · see citing works
A kinase in the life of the β cell
Accili, D. (2001) · Journal of Clinical Investigation · doi:10.1172/jci200114454 · Cited by 3 · see citing works
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Sorted by citations
Critical nodes in signalling pathways: insights into insulin action
Taniguchi, C. M., Emanuelli, B., & Kahn, C. R. (2006) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm1837 · Cited by 2,760 · see citing works
The Human Obesity Gene Map: The 2005 Update
Rankinen, T., Zuberi, A., Chagnon, Y. C., Weisnagel, S. J., Argyropoulos, G., Walts, B., Pérusse, L., & Bouchard, C. (2006) · Obesity · doi:10.1038/oby.2006.71 · Cited by 1,119 · see citing works
Diabetes, Obesity, and the Brain
Schwartz, M. W., & Porte, D. (2005) · Science · doi:10.1126/science.1104344 · Cited by 841 · see citing works
Insulin Action in Brain Regulates Systemic Metabolism and Brain Function
Kleinridders, A., Ferris, H. A., Cai, W., & Kahn, C. R. (2014) · Diabetes · doi:10.2337/db14-0568 · Cited by 688 · see citing works
Regulation of insulin synthesis and secretion and pancreatic Beta-cell dysfunction in diabetes.
Fu, Z., Gilbert, E. R., & Liu, D. (2013) · PubMed · Cited by 600 · see citing works
Recent advances in understanding leptin signaling and leptin resistance
Morris, D. L., & Rui, L. (2009) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00274.2009 · Cited by 467 · see citing works
Very Slow Turnover of β-Cells in Aged Adult Mice
Teta, M., Long, S. Y., Wartschow, L. M., Rankin, M. M., & Kushner, J. A. (2005) · Diabetes · doi:10.2337/diabetes.54.9.2557 · Cited by 465 · see citing works
Leptin signaling and leptin resistance
Zhou, Y., & Rui, L. (2013) · Frontiers of Medicine · doi:10.1007/s11684-013-0263-5 · Cited by 417 · see citing works
Emerging role of the brain in the homeostatic regulation of energy and glucose metabolism
Roh, E., Song, D. K., & Kim, M.-S. (2016) · Experimental & Molecular Medicine · doi:10.1038/emm.2016.4 · Cited by 391 · see citing works
Leptin and the Central Nervous System Control of Glucose Metabolism
Morton, G. J., & Schwartz, M. W. (2011) · Physiological Reviews · doi:10.1152/physrev.00007.2010 · Cited by 338 · see citing works
“mild obesity and insulin resistance (27, 97, 105).”
BackgroundInsulin Signaling in the Central Nervous System
Porte, D., Baskin, D. G., & Schwartz, M. W. (2005) · Diabetes · doi:10.2337/diabetes.54.5.1264 · Cited by 336 · see citing works
Terauchi, Y., Takamoto, I., Kubota, N., Matsui, J., Suzuki, R., Komeda, K., Hara, A., Toyoda, Y., Miwa, I., Aizawa, S., et al. (2007) · Journal of Clinical Investigation · doi:10.1172/jci17645 · Cited by 327 · see citing works
Self-citationThe Human Obesity Gene Map: The 2004 Update
Përusse, L., Rankinen, T., Zuberi, A. R., Chagnon, Y. C., Weisnagel, S. J., Argyropoulos, G. A., Walts, B., Snyder, E. E., & Bouchard, C. (2005) · Obesity Research · doi:10.1038/oby.2005.50 · Cited by 326 · see citing works
Kubota, N., Terauchi, Y., Kubota, T., Kumagai, H., Itoh, S., Satoh, H., Yano, W., Ogata, H., Tokuyama, K., Takamoto, I., et al. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m505649200 · Cited by 327 · see citing works
Self-citationConditional Gene Targeting in Mouse Pancreatic β-Cells
Wicksteed, B. L., Briššová, M., Yan, W., Opland, D. M., Plank, J. L., Reinert, R. B., Dickson, L. M., Tamarina, N. A., Philipson, L. H., Shostak, A., et al. (2010) · Diabetes · doi:10.2337/db10-0624 · Cited by 321 · see citing works
Morton, G. J., Gelling, R. W., Niswender, K. D., Morrison, C. D., Rhodes, C. J., & Schwartz, M. W. (2005) · Cell Metabolism · doi:10.1016/j.cmet.2005.10.009 · Cited by 292 · see citing works
Pancreatic signals controlling food intake; insulin, glucagon and amylin
Woods, S. C., Lutz, T. A., Geary, N., & Langhans, W. (2006) · Philosophical Transactions of the Royal Society B Biological Sciences · doi:10.1098/rstb.2006.1858 · Cited by 286 · see citing works
ER stress and SREBP-1 activation are implicated in β-cell glucolipotoxicity
Wang, H., Kouri, G., & Wollheim, C. B. (2005) · Journal of Cell Science · doi:10.1242/jcs.02513 · Cited by 265 · see citing works
Molecular regulation of pancreatic β-cell mass development, maintenance, and expansion
Ackermann, A. M., & Gannon, M. (2007) · Journal of Molecular Endocrinology · doi:10.1677/jme-06-0053 · Cited by 262 · see citing works
Fast Food, Central Nervous System Insulin Resistance, and Obesity
ISGANAITIS, E. M., & Lustig, R. H. (2005) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/01.atv.0000186208.06964.91 · Cited by 261 · see citing works
Etiology of Metabolic Syndrome and Dietary Intervention
Xu, H., Li, X., Adams, H. M., Kubena, K. S., & Guo, S. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms20010128 · Cited by 258 · see citing works
RIP-Cre Revisited, Evidence for Impairments of Pancreatic β-Cell Function
Lee, J., Ristow, M., Lin, X., White, M. F., Magnuson, M. A., & Hennighausen, L. G. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m512373200 · Cited by 246 · see citing works
Kubota, N., Kubota, T., Itoh, S., Kumagai, H., Kozono, H., Takamoto, I., Mineyama, T., Ogata, H., Tokuyama, K., Ohsugi, M., et al. (2008) · Cell Metabolism · doi:10.1016/j.cmet.2008.05.007 · Cited by 244 · see citing works
Self-citationThe role of insulin receptor substrate 2 in hypothalamic and β cell function
Choudhury, A. I., Heffron, H., Smith, M. A., Al‐Qassab, H., Xu, A. W., Selman, C., Simmgen, M., Clements, M., Claret, M., MacColl, G., et al. (2005) · Journal of Clinical Investigation · doi:10.1172/jci24445 · Cited by 241 · see citing works
SerpinB1 Promotes Pancreatic β-Cell Proliferation
Ouaamari, A. E., Dirice, E., Gedeon, N., Hu, J., Zhou, J.-Y., Shirakawa, J., Hou, L., Goodman, J. L., Karampelias, C., Qiang, G., et al. (2015) · Cell Metabolism · doi:10.1016/j.cmet.2015.12.001 · Cited by 207 · see citing works
Irs1 and Irs2 signaling is essential for hepatic glucose homeostasis and systemic growth
Dong, X. C., Park, S., Lin, X., Copps, K. D., Yi, X., & White, M. F. (2005) · Journal of Clinical Investigation · doi:10.1172/jci25735 · Cited by 230 · see citing works
Ablation of PDK1 in pancreatic β cells induces diabetes as a result of loss of β cell mass
Hashimoto, N., Kido, Y., Uchida, T., Asahara, S., Shigeyama, Y., Matsuda, T., Takeda, A., Tsuchihashi, D., Nishizawa, A., Ogawa, W., et al. (2006) · Nature Genetics · doi:10.1038/ng1774 · Cited by 227 · see citing works
Self-citationThe role of FOXO1 in β-cell failure and type 2 diabetes mellitus
Kitamura, T. (2013) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2013.157 · Cited by 222 · see citing works
GABAergic RIP-Cre Neurons in the Arcuate Nucleus Selectively Regulate Energy Expenditure
Kong, D., Tong, Q., Ye, C., Koda, S., Fuller, P. M., Krashes, M. J., Vong, L., Ray, R. S., Olson, D. P., & Lowell, B. B. (2012) · Cell · doi:10.1016/j.cell.2012.09.020 · Cited by 215 · see citing works
Insulin Signaling in the Pancreatic β-Cell
Leibiger, I. B., Leibiger, B., & Berggren, P. (2008) · Annual Review of Nutrition · doi:10.1146/annurev.nutr.28.061807.155530 · Cited by 221 · see citing works
Recipes for Creating Animal Models of Diabetic Cardiovascular Disease
Hsueh, W. A., Abel, E. D., Breslow, J. L., Maeda, N., Davis, R. C., Fisher, E. A. A., Dansky, H. M., McClain, D. A., McIndoe, R., Wassef, M. K., et al. (2007) · Circulation Research · doi:10.1161/01.res.0000266449.37396.1f · Cited by 219 · see citing works
mTORC1 Signaling: A Double-Edged Sword in Diabetic β Cells
Ardestani, A. D., Lupše, B., Kido, Y., Leibowitz, G., & Maedler, K. (2017) · Cell Metabolism · doi:10.1016/j.cmet.2017.11.004 · Cited by 194 · see citing works
Critical Role for Hypothalamic mTOR Activity in Energy Balance
Mori, H., Inoki, K., Münzberg, H., Opland, D. M., Faouzi, M., Villanueva, E. C., Ikenoue, T., Kwiatkowski, D. J., MacDougald, O. A., Myers, M. G., et al. (2009) · Cell Metabolism · doi:10.1016/j.cmet.2009.03.005 · Cited by 188 · see citing works
Protein Tyrosine Phosphatases in Hypothalamic Insulin and Leptin Signaling
Zhang, Z., Dodd, G. T., & Tiganis, T. (2015) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2015.07.003 · Cited by 181 · see citing works
Biphasic Response of Pancreatic β-Cell Mass to Ablation of Tuberous Sclerosis Complex 2 in Mice
Shigeyama, Y., Kobayashi, T., Kido, Y., Hashimoto, N., Asahara, S., Matsuda, T., Takeda, A., Inoue, T., Shibutani, Y., Koyanagi, M., et al. (2008) · Molecular and Cellular Biology · doi:10.1128/mcb.01695-07 · Cited by 177 · see citing works
Self-citationThe FoxO transcription factors and metabolic regulation
Nakae, J., Oki, M., & Cao, Y. (2008) · FEBS Letters · doi:10.1016/j.febslet.2007.11.025 · Cited by 176 · see citing works
Activation of hypothalamic S6 kinase mediates diet-induced hepatic insulin resistance in rats
Ono, H., Pocai, A., Wang, Y., Sakoda, H., Asano, T., Backer, J., Schwartz, G. J., & Rossetti, L. (2008) · Journal of Clinical Investigation · doi:10.1172/jci34277 · Cited by 176 · see citing works
Mechanisms of Compensatory β-Cell Growth in Insulin-Resistant Rats
Jetton, T. L., Lausier, J., LaRock, K., Trotman, W., Larmie, B. L., Habibovic, A., Peshavaria, M., & Leahy, J. L. (2005) · Diabetes · doi:10.2337/diabetes.54.8.2294 · Cited by 171 · see citing works
Insulin action in the brain contributes to glucose lowering during insulin treatment of diabetes
Gelling, R. W., Morton, G. J., Morrison, C. D., Niswender, K. D., Myers, M. G., Rhodes, C. J., & Schwartz, M. W. (2006) · Cell Metabolism · doi:10.1016/j.cmet.2005.11.013 · Cited by 169 · see citing works
Kubota, T., Kubota, N., & Kadowaki, T. (2017) · Cell Metabolism · doi:10.1016/j.cmet.2017.03.004 · Cited by 169 · see citing works
Self-citationGerman, J., Kim, F., Schwartz, G. J., Havel, P. J., Rhodes, C. J., Schwartz, M. W., & Morton, G. J. (2009) · Endocrinology · doi:10.1210/en.2009-0445 · Cited by 164 · see citing works
Cytokines in the Progression of Pancreatic β -Cell Dysfunction
Wang, C., Guan, Y., & Yang, J. (2010) · International Journal of Endocrinology · doi:10.1155/2010/515136 · Cited by 163 · see citing works
Lustig, R. H. (2006) · Nature Clinical Practice Endocrinology & Metabolism · doi:10.1038/ncpendmet0220 · Cited by 162 · see citing works
Role of histone and transcription factor acetylation in diabetes pathogenesis
Gray, S. G., & MEYTS, P. D. (2005) · Diabetes/Metabolism Research and Reviews · doi:10.1002/dmrr.559 · Cited by 143 · see citing works
Central Nervous System Regulation of Food Intake
Schwartz, M. W. (2006) · Obesity · doi:10.1038/oby.2006.275 · Cited by 146 · see citing works
Kubota, N., Kubota, T., Kajiwara, E., Iwamura, T., Kumagai, H., Watanabe, T., Inoue, M., Takamoto, I., Sasako, T., Kumagai, K., et al. (2016) · Nature Communications · doi:10.1038/ncomms12977 · Cited by 143 · see citing works
Self-citationKoch, C. E., Augustine, R. A., Steger, J., Ganjam, G. K., Benzler, J., Pracht, C., Lowe, C., Schwartz, M. W., Shepherd, P. R., Anderson, G. M., et al. (2010) · Journal of Neuroscience · doi:10.1523/jneurosci.3202-10.2010 · Cited by 136 · see citing works
Kaneko, K., Ueki, K., Takahashi, N. K., Hashimoto, S., Okamoto, M., Awazawa, M., Okazaki, Y., Ohsugi, M., Inabe, K., Umehara, T., et al. (2010) · Cell Metabolism · doi:10.1016/j.cmet.2010.11.005 · Cited by 123 · see citing works
Self-citationBouzakri, K., Plomgaard, P., Berney, T., Donath, M. Y., Pedersen, B. K., & Halban, P. A. (2011) · Diabetes · doi:10.2337/db10-1178 · Cited by 122 · see citing works
Tang, T., Abbott, M. J., Ahmadian, M., Lopes, A. B., Wang, Y., & Sul, H. S. (2013) · Cell Metabolism · doi:10.1016/j.cmet.2013.10.012 · Cited by 115 · see citing works
Glucose Regulates Foxo1 Through Insulin Receptor Signaling in the Pancreatic Islet β-cell
Martinez, S. C., CRAS-MÉNEUR, C. M. H., Bernal‐Mizrachi, E., & Permutt, M. A. (2006) · Diabetes · doi:10.2337/db05-0678 · Cited by 115 · see citing works
CNS Regulation of Glucose Homeostasis
Lam, C., Chari, M., & Lam, T. K. T. (2009) · Physiology · doi:10.1152/physiol.00003.2009 · Cited by 110 · see citing works
Hypothalamic leptin regulation of energy homeostasis and glucose metabolism
Morton, G. J. (2007) · The Journal of Physiology · doi:10.1113/jphysiol.2007.135590 · Cited by 112 · see citing works
Shirakawa, J., Fernandez, M., Takatani, T., Ouaamari, A. E., Jungtrakoon, P., Okawa, E. R., Zhang, W., Peng, Y., Doria, A., & Kulkarni, R. (2017) · Cell Metabolism · doi:10.1016/j.cmet.2017.02.004 · Cited by 108 · see citing works
Deletion of SOCS7 leads to enhanced insulin action and enlarged islets of Langerhans
Banks, A. S., Li, J., McKeag, L., Hribal, M. L., Kashiwada, M., Accili, D., & Rothman, P. B. (2005) · Journal of Clinical Investigation · doi:10.1172/jci23853 · Cited by 106 · see citing works
Brain expression of Cre recombinase driven by pancreas‐specific promoters
Song, J., Xu, Y., Hu, X., Choi, B. J., & Tong, Q. (2010) · genesis · doi:10.1002/dvg.20672 · Cited by 105 · see citing works
Tissue‐specific insulin signaling in the regulation of metabolism and aging
Zhang, J., & Liu, F. (2014) · IUBMB Life · doi:10.1002/iub.1293 · Cited by 100 · see citing works
Insm1 cooperates with Neurod1 and Foxa2 to maintain mature pancreatic β‐cell function
Jia, S., Ivanov, A., Blasevic, D., Müller, T. H., Purfürst, B., Sun, W., Chen, W., Poy, M. N., Rajewsky, N., & Birchmeier, C. (2015) · The EMBO Journal · doi:10.15252/embj.201490819 · Cited by 103 · see citing works
Critical roles for the TSC-mTOR pathway in β-cell function
Mori, H., Inoki, K., Opland, D. M., Münzberg, H., Villanueva, E. C., Faouzi, M., Ikenoue, T., Kwiatkowski, D. J., MacDougald, O. A., Myers, M. G., et al. (2009) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00262.2009 · Cited by 103 · see citing works
Kato, T., Shimano, H., Yamamoto, T., Ishikawa, M., Kumadaki, S., Matsuzaka, T., Nakagawa, Y., Yahagi, N., Nakakuki, M., Hasty, A. H., et al. (2008) · Diabetes · doi:10.2337/db06-1806 · Cited by 102 · see citing works
Distribution of insulin receptor substrate-2 in brain areas involved in energy homeostasis
Pardini, A. W., Hồng, N. T., Figlewicz, D. P., Baskin, D. G., Williams, D. L., Kim, F., & Schwartz, M. W. (2006) · Brain Research · doi:10.1016/j.brainres.2006.06.109 · Cited by 101 · see citing works
Present status of clinical deployment of glucokinase activators
Nakamura, A., & Terauchi, Y. (2014) · Journal of Diabetes Investigation · doi:10.1111/jdi.12294 · Cited by 99 · see citing works
Self-citationLipotoxicity and β Cell Maintenance in Obesity and Type 2 Diabetes
Ye, R., Onodera, T., & Scherer, P. E. (2019) · Journal of the Endocrine Society · doi:10.1210/js.2018-00372 · Cited by 94 · see citing works
Essential Role of Pten in Body Size Determination and Pancreatic β-Cell Homeostasis In Vivo
Nguyen, K.-T. T., Tajmir, P., Lin, C. H., Liadis, N., Zhu, X.-D., Eweida, M., Karaman, G., Cai, F., Wang, R., Kitamura, T., et al. (2006) · Molecular and Cellular Biology · doi:10.1128/mcb.00238-06 · Cited by 96 · see citing works
Role of malonyl-CoA in heart disease and the hypothalamic control of obesity
Folmes, C. D. L., & LOPASCHUK, G. (2006) · Cardiovascular Research · doi:10.1016/j.cardiores.2006.10.008 · Cited by 95 · see citing works
Shimizu, H., Oh‐I, S., Okada, S., & Mori, M. (2007) · Endocrine Journal · doi:10.1507/endocrj.kr-85 · Cited by 93 · see citing works
Chang, C., Yeh, S., Lee, S. O., & Chang, T. (2013) · Nuclear Receptor Signaling · doi:10.1621/nrs.11001 · Cited by 91 · see citing works
New Insights into the Roles of Insulin/IGF-I in the Development and Maintenance of β-Cell Mass
Kulkarni, R. (2005) · Reviews in Endocrine and Metabolic Disorders · doi:10.1007/s11154-005-3051-y · Cited by 92 · see citing works
Takamoto, I., Kubota, N., Nakaya, K., Kumagai, K., Hashimoto, S., Kubota, T., Inoue, M., Kajiwara, E., Katsuyama, H., Obata, A., et al. (2013) · Diabetologia · doi:10.1007/s00125-013-3131-6 · Cited by 89 · see citing works
Self-citationLeung, Y., Ahmed, I., Sheu, L., Gao, X., Hara, M., Tsushima, R. G., Diamant, N. E., & Gaisano, H. Y. (2006) · Endocrinology · doi:10.1210/en.2005-1249 · Cited by 83 · see citing works
Cantley, J., Choudhury, A. I., Asare‐Anane, H., Selman, C., Lingard, S. J., Heffron, H., Herrera, P. L., Persaud, S. J., & Withers, D. J. (2007) · Diabetologia · doi:10.1007/s00125-007-0637-9 · Cited by 79 · see citing works
Roles of FoxO1 and Sirt1 in the central regulation of food intake
Sasaki, T., & Kitamura, T. (2010) · Endocrine Journal · doi:10.1507/endocrj.k10e-320 · Cited by 79 · see citing works
Kubota, T., Inoue, M., Kubota, N., Takamoto, I., Mineyama, T., Iwayama, K., Tokuyama, K., Moroi, M., Ueki, K., Yamauchi, T., et al. (2018) · Nature Communications · doi:10.1038/s41467-018-07358-9 · Cited by 78 · see citing works
Self-citationMetallothionein and Catalase Sensitize to Diabetes in Nonobese Diabetic Mice
Li, X., Chen, H., & Epstein, P. N. (2006) · Diabetes · doi:10.2337/db05-1357 · Cited by 78 · see citing works
IRS-2 Deficiency Impairs NMDA Receptor-Dependent Long-term Potentiation
Martín, E. D., Sánchez‐Pérez, A. M., Trejo, J. L., Martin-Aldana, J. A., Cano‐Jaimez, M., Pons, S., Umanzor, C. A., Menes, L., White, M. F., & Burks, D. J. (2011) · Cerebral Cortex · doi:10.1093/cercor/bhr216 · Cited by 78 · see citing works
Costello, D. A., Claret, M., Al‐Qassab, H., Plattner, F., Irvine, E. E., Choudhury, A. I., Giese, K.-P., Withers, D. J., & Pedarzani, P. (2012) · PLoS ONE · doi:10.1371/journal.pone.0031124 · Cited by 73 · see citing works
Caldérari, S., Gangnerau, M.-N., Thibault, M., Meile, M.-J., Kassis, N., Álvarez, C., Portha, B., & Serradas, P. (2007) · Diabetologia · doi:10.1007/s00125-007-0676-2 · Cited by 75 · see citing works
Doan, K. V., Choi, Y., Moh, S. H., Kinyua, A. W., & Kim, K. W. (2014) · Frontiers in Psychology · doi:10.3389/fpsyg.2014.00846 · Cited by 72 · see citing works
Roman, E. A. F. R., Reis, D., Romanatto, T., Maimoni, D., Ferreira, E. A., Santos, G. A., Torsoni, A. S., Velloso, L. A., & Torsoni, M. A. (2010) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2009.08.007 · Cited by 71 · see citing works
Growth factor control of pancreatic islet regeneration and function
Aßmann, A., Hinault, C., & Kulkarni, R. (2008) · Pediatric Diabetes · doi:10.1111/j.1399-5448.2008.00468.x · Cited by 71 · see citing works
A Review of Islet of Langerhans Degeneration in Rodent Models of Type 2 Diabetes
Nugent, D., Smith, D. M., & Jones, H. B. (2008) · Toxicologic Pathology · doi:10.1177/0192623308318209 · Cited by 70 · see citing works
Hardy, A. B., Wijesekara, N., Genkin, I., Prentice, K. J., Bhattacharjee, A., Kong, D., Chimienti, F., & Wheeler, M. B. (2012) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00448.2011 · Cited by 66 · see citing works
Distinct In Vivo Roles of Caspase-8 in β-Cells in Physiological and Diabetes Models
Liadis, N., Salmena, L., Kwan, E. P., Tajmir, P., Schroer, S. A., Radziszewska, A., Xie, L., Sheu, L., Eweida, M., Xu, S., et al. (2007) · Diabetes · doi:10.2337/db06-1771 · Cited by 68 · see citing works
mTOR controls ChREBP transcriptional activity and pancreatic β cell survival under diabetic stress
Chau, G. C., Im, D. U., Kang, T. M., Bae, J. M., Kim, W., Pyo, S., Moon, E.-Y., & Um, S. H. (2017) · Journal of Cell Biology · doi:10.1083/jcb.201701085 · Cited by 67 · see citing works
PDK-1/FoxO1 pathway in POMC neurons regulatesPomcexpression and food intake
Iskandar, K., Cao, Y., Hayashi, Y., Nakata, M., Takano, E., Yada, T., Zhang, C., Ogawa, W., Oki, M., Chua, S. C., et al. (2010) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00512.2009 · Cited by 67 · see citing works
Self-citationIRS2 takes center stage in the development of type 2 diabetes
Brady, M. (2004) · Journal of Clinical Investigation · doi:10.1172/jci23108 · Cited by 66 · see citing works
Wang, L., Opland, D. M., Tsai, S. J., Luk, C. T., Schroer, S. A., Allison, M. B., Elia, A., Furlonger, C. L., Suzuki, A., Paige, C. J., et al. (2014) · Nature Medicine · doi:10.1038/nm.3527 · Cited by 66 · see citing works
Muraoka, T., Aoki, K., Iwasaki, T., Shinoda, K., Nakamura, A., Aburatani, H., Mori, S., Tokuyama, K., Kubota, N., Kadowaki, T., et al. (2010) · Metabolism · doi:10.1016/j.metabol.2010.06.008 · Cited by 64 · see citing works
Self-citationRabiee, A., Krüger, M., Ardenkjær-Skinnerup, J., Kahn, C. R., & Emanuelli, B. (2018) · Cellular Signalling · doi:10.1016/j.cellsig.2018.03.003 · Cited by 62 · see citing works
Bouzakri, K., Ribaux, P., & Halban, P. A. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.048058 · Cited by 60 · see citing works
Impact of Small-Molecule Glucokinase Activator on Glucose Metabolism and β-Cell Mass
Nakamura, A., Terauchi, Y., Ohyama, S., Kubota, J., Shimazaki, H., Nambu, T., Takamoto, I., Kubota, N., Eiki, J., Yoshioka, N., et al. (2008) · Endocrinology · doi:10.1210/en.2008-1183 · Cited by 59 · see citing works
Self-citationJiang, S., Shen, D., Jia, W., Han, X., Shen, N., Tao, W., Gao, X., Xue, B., & Li, C. (2015) · The Journal of Pathology · doi:10.1002/path.4652 · Cited by 57 · see citing works
Molecular Mechanism of Moderate Insulin Resistance in Adiponectin-Knockout Mice
Yano, W., Kubota, N., Itoh, S., Kubota, T., Awazawa, M., Moroi, M., Sugi, K., Takamoto, I., Ogata, H., Tokuyama, K., et al. (2008) · Endocrine Journal · doi:10.1507/endocrj.k08e-093 · Cited by 57 · see citing works
Self-citationHistone deacetylase regulates insulin signaling via two pathways in pancreatic β cells
Kawada, Y., Asahara, S., Sugiura, Y., Sato, A., Furubayashi, A., Kawamura, M., Bartolomé, A., Terashi, E., Takai, T., Kanno, A., et al. (2017) · PLoS ONE · doi:10.1371/journal.pone.0184435 · Cited by 57 · see citing works
Chapter 13 Phosphorylation of IRS Proteins
Sun, X., & Liu, F. (2009) · Vitamins and hormones · doi:10.1016/s0083-6729(08)00613-4 · Cited by 56 · see citing works
Michael, E. S., Covic, L., & Kuliopulos, A. (2019) · Journal of Biological Chemistry · doi:10.1074/jbc.ra118.005464 · Cited by 56 · see citing works
Hyperglycemia Is Associated with Psoriatic Inflammation in Both Humans and Mice
Ikumi, K., Odanaka, M., Shime, H., Imai, M., Osaga, S., Taguchi, O., Nishida, E., Hemmi, H., Kaisho, T., Morita, A., et al. (2019) · Journal of Investigative Dermatology · doi:10.1016/j.jid.2019.01.029 · Cited by 55 · see citing works
Ueno, N., Inui, A., Kalra, P. S., & Kalra, S. P. (2006) · Peptides · doi:10.1016/j.peptides.2006.03.006 · Cited by 53 · see citing works
Tan, D., Tseng, H. H. L., Zhong, Z., Wang, S., Vong, C. T., & Wang, Y. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms231910988 · Cited by 53 · see citing works
Zhang, S. S., Hao, E., Yu, J., Liu, W., Wang, J., Levine, F., & Feng, G. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0811715106 · Cited by 50 · see citing works
- Authors
- Kubota, N., Terauchi, Y., Tobe, K., Yano, W., Suzuki, R., Ueki, K., Takamoto, I., Satoh, H., Maki, T., Kubota, T., Moroi, M., Okada-Iwabu, M., Ezaki, O., Nagai, R., Ueta, Y., Kadowaki, T., & Noda, T.
- Affiliations
- The University of Tokyo (JP)
- Japan Science and Technology Agency (JP)
- Toho University (JP)
- National Institute of Health and Nutrition (JP)
- University of Occupational and Environmental Health Japan (JP)
- Tohoku University (JP)
- Corresponding author
- Kadowaki, Takashi
- ORCID
- Venue
- Journal of Clinical Investigation
- Published
- 2004-10-01
- Volume
- 114
- Issue
- 7
- Pages
- 917-927
- ISSN
- 0021-9738 (ISSN-L)
- PMC
- PMC518663
- OpenAlex
- W2140622624
- Cited by
- 239
- References
- 39
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 5 · 2023: 3 · 2022: 5 · 2021: 6 · 2020: 6 · 2019: 9 · 2018: 9 · 2017: 8 · 2016: 6 · 2015: 13 · 2014: 15 · 2013: 14 · 2012: 11
- FWCI
- 17.69
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Investigation (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Kowa Company
- Ministry of Education, Culture, Sports, Science and Technology
- Kanae Foundation for the Promotion of Medical Science
- Japan Society for the Promotion of Science (10NP0201)
- Topics
- Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Diabetes and associated disorders
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Keywords
- insulin receptor substrate 2, pancreatic beta cells, hypothalamus, arcuate nucleus, leptin resistance, obesity, beta-cell mass, beta-cell proliferation, insulin secretion, impaired glucose tolerance, hepatic insulin resistance, type 2 diabetes, insulin sensitivity
- MeSH terms
- Animals, Arcuate Nucleus of Hypothalamus, Blood Glucose, Body Weight, Cell Division, Diet, Female, Hyperlipidemias, Insulin, Insulin Resistance, Islets of Langerhans, Male, Mice, Inbred C57BL, Obesity, Phosphoproteins, RNA, Messenger, Tissue Distribution, Transcription Factors, Signal Transduction, Glucose Intolerance, Mice, Knockout, Leptin, Caloric Restriction, Intracellular Signaling Peptides and Proteins, Mice, Insulin Receptor Substrate Proteins
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