Cited by 239Pancreatic function and diabetesDiabetes and associated disordersDiabetes Treatment and Management

The DOI matches its Crossref record; 40 of the 40 references it cites were found in a registry or an index.

Insulin receptor substrate 2 plays a crucial role in β cells and the hypothalamus

Open access

Kubota, Naoto, Terauchi, Yasuo, Tobe, Kazuyuki, Yano, Wataru, Suzuki, Ryo, Ueki, Kohjiro, Takamoto, Iseki, Satoh, Hidemi, Maki, Toshiyuki, Kubota, Tetsuya, Moroi, Masao, Okada-Iwabu, Miki, Ezaki, Osamu, Nagai, Ryozo, Ueta, Yoichi, Kadowaki, Takashi, Noda, Tetsuo·2004·Journal of Clinical Investigation

DOI 10.1172/jci21484PMC PMC518663

Open this paper in CoChat — free account Open PDF

Abstract

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.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

Integrity signals

Registry

Crossref · 10.1172/jci21484

Cites

40 of 40 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

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
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
Cellular mechanisms of insulin resistance
Shulman, G. I. (2000) · Journal of Clinical Investigation · doi:10.1172/jci10583 · Cited by 2,714
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
Disruption of IRS-2 causes type 2 diabetes in mice
Withers, D. J., Gutierrez, J. S., Towery, H. H., Burks, D. J., Ren, J., Previs, S. F., Zhang, Y., Bernal, D., Pons, S., Shulman, G. I., et al. (1998) · Nature · doi:10.1038/36116 · Cited by 1,775
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
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 1,351
Self-citation
Alternative 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
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
Self-citation
Tissue-Specific Knockout of the Insulin Receptor in Pancreatic β Cells Creates an Insulin Secretory Defect Similar to that in Type 2 Diabetes
Kulkarni, 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

Show all 39 references

Research works printed but not linked: 1

10.1210/en.136.10.4182 · DOI

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
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
Diabetes, Obesity, and the Brain
Schwartz, M. W., & Porte, D. (2005) · Science · doi:10.1126/science.1104344 · Cited by 841
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 625
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
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 484
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
Leptin signaling and leptin resistance
Zhou, Y., & Rui, L. (2013) · Frontiers of Medicine · doi:10.1007/s11684-013-0263-5 · Cited by 358
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 407
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
“mild obesity and insulin resistance (27, 97, 105).”
Background
Insulin 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 339
Glucokinase and IRS-2 are required for compensatory cell hyperplasia in response to high-fat diet-induced insulin resistance
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
Self-citation
The 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 328
Pioglitazone Ameliorates Insulin Resistance and Diabetes by Both Adiponectin-dependent and -independent Pathways
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 331
Self-citation
Conditional 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 324
Leptin regulates insulin sensitivity via phosphatidylinositol-3-OH kinase signaling in mediobasal hypothalamic neurons
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
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 301
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 268
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
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 262
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 271
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 252
Dynamic Functional Relay between Insulin Receptor Substrate 1 and 2 in Hepatic Insulin Signaling during Fasting and Feeding
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
Self-citation
The 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 244
SerpinB1 Promotes Pancreatic β Cell Proliferation
Ouaamari, A. E., Dirice, E., Gedeon, N., Hu, J., Zhou, J.-Y., Shirakawa, J., Hou, L., Goodman, J., Karampelias, C., Qiang, G., et al. (2015) · Cell Metabolism · doi:10.1016/j.cmet.2015.12.001 · Cited by 236
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 239
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
Self-citation
The 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 225
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
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
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 221
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 198
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 189
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 186
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 184
Self-citation
The 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
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 183
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 172
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
Imbalanced Insulin Actions in Obesity and Type 2 Diabetes: Key Mouse Models of Insulin Signaling Pathway
Kubota, T., Kubota, N., & Kadowaki, T. (2017) · Cell Metabolism · doi:10.1016/j.cmet.2017.03.004 · Cited by 174
Self-citation
Hypothalamic Leptin Signaling Regulates Hepatic Insulin Sensitivity via a Neurocircuit Involving the Vagus Nerve
German, 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
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 173
Childhood obesity: behavioral aberration or biochemical drive? Reinterpreting the First Law of Thermodynamics
Lustig, R. H. (2006) · Nature Clinical Practice Endocrinology & Metabolism · doi:10.1038/ncpendmet0220 · Cited by 162
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 144
Central Nervous System Regulation of Food Intake
Schwartz, M. W. (2006) · Obesity · doi:10.1038/oby.2006.275 · Cited by 150
Differential hepatic distribution of insulin receptor substrates causes selective insulin resistance in diabetes and obesity
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
Self-citation
Leptin Rapidly Improves Glucose Homeostasis in Obese Mice by Increasing Hypothalamic Insulin Sensitivity
Koch, 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 139
Class IA Phosphatidylinositol 3-Kinase in Pancreatic β Cells Controls Insulin Secretion by Multiple Mechanisms
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 125
Self-citation
Bimodal Effect on Pancreatic β-Cells of Secretory Products From Normal or Insulin-Resistant Human Skeletal Muscle
Bouzakri, K., Plomgaard, P., Berney, T., Donath, M. Y., Pedersen, B. K., & Halban, P. A. (2011) · Diabetes · doi:10.2337/db10-1178 · Cited by 122
Desnutrin/ATGL Activates PPARδ to Promote Mitochondrial Function for Insulin Secretion in Islet β Cells
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 113
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
CNS Regulation of Glucose Homeostasis
Lam, C., Chari, M., & Lam, T. K. T. (2009) · Physiology · doi:10.1152/physiol.00003.2009 · Cited by 117
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 114
Insulin Signaling Regulates the FoxM1/PLK1/CENP-A Pathway to Promote Adaptive Pancreatic β Cell Proliferation
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
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 104
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 107
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 105
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 107
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 104
Palmitate Impairs and Eicosapentaenoate Restores Insulin Secretion Through Regulation of SREBP-1c in Pancreatic Islets
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 103
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
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
Self-citation
Lipotoxicity 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 96
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 99
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 98
Leptin Resistance and Obesity
Shimizu, H., Oh‐I, S., Okada, S., & Mori, M. (2007) · Endocrine Journal · doi:10.1507/endocrj.kr-85 · Cited by 97
Androgen Receptor (AR) Pathophysiological Roles in Androgen Related Diseases in Skin, Metabolism Syndrome, Bone/Muscle and Neuron/Immune Systems: Lessons Learned from Mice Lacking AR in Specific Cells
Chang, C., Yeh, S., Lee, S. O., & Chang, T. (2013) · Nuclear Receptor Signaling · doi:10.1621/nrs.11001 · Cited by 92
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 90
TCF7L2 in mouse pancreatic beta cells plays a crucial role in glucose homeostasis by regulating beta cell mass
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
Self-citation
Insulin Regulates Islet α-Cell Function by Reducing KATP Channel Sensitivity to Adenosine 5′-Triphosphate Inhibition
Leung, 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 82
Pancreatic deletion of insulin receptor substrate 2 reduces beta and alpha cell mass and impairs glucose homeostasis in mice
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
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 80
Downregulation of macrophage Irs2 by hyperinsulinemia impairs IL-4-indeuced M2a-subtype macrophage activation in obesity
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 80
Self-citation
Metallothionein 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
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 80
Brain Deletion of Insulin Receptor Substrate 2 Disrupts Hippocampal Synaptic Plasticity and Metaplasticity
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
Defective IGF2 and IGF1R protein production in embryonic pancreas precedes beta cell mass anomaly in the Goto–Kakizaki rat model of type 2 diabetes
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
Leptin and insulin signaling in dopaminergic neurons: relationship between energy balance and reward system
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 71
Central leptin action improves skeletal muscle AKT, AMPK, and PGC1α activation by hypothalamic PI3K-dependent mechanism
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
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 72
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 73
Effects of high-fat diet feeding on Znt8-null mice: differences between β-cell and global knockout of Znt8
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 69
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 69
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
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
Self-citation
IRS2 takes center stage in the development of type 2 diabetes
Brady, M. (2004) · Journal of Clinical Investigation · doi:10.1172/jci23108 · Cited by 67
Pten deletion in RIP-Cre neurons protects against type 2 diabetes by activating the anti-inflammatory reflex
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 67
Ezetimibe decreases SREBP-1c expression in liver and reverses hepatic insulin resistance in mice fed a high-fat diet
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
Self-citation
Distinct signalling properties of insulin receptor substrate (IRS)-1 and IRS-2 in mediating insulin/IGF-1 action
Rabiee, A., Krüger, M., Ardenkjær-Skinnerup, J., Kahn, C. R., & Emanuelli, B. (2018) · Cellular Signalling · doi:10.1016/j.cellsig.2018.03.003 · Cited by 68
Silencing Mitogen-activated Protein 4 Kinase 4 (MAP4K4) Protects Beta Cells from Tumor Necrosis Factor-α-induced Decrease of IRS-2 and Inhibition of Glucose-stimulated Insulin Secretion
Bouzakri, K., Ribaux, P., & Halban, P. A. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.048058 · Cited by 61
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
Self-citation
GGPPS ‐mediated Rab27A geranylgeranylation regulates β cell dysfunction during type 2 diabetes development by affecting insulin granule docked pool formation
Jiang, 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
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 58
Self-citation
Histone 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
Chapter 13 Phosphorylation of IRS Proteins
Sun, X., & Liu, F. (2009) · Vitamins and hormones · doi:10.1016/s0083-6729(08)00613-4 · Cited by 57
Trace amine–associated receptor 1 (TAAR1) promotes anti-diabetic signaling in insulin-secreting cells
Michael, E. S., Covic, L., & Kuliopulos, A. (2019) · Journal of Biological Chemistry · doi:10.1074/jbc.ra118.005464 · Cited by 56
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
Leptin transgene expression in the hypothalamus enforces euglycemia in diabetic, insulin-deficient nonobese Akita mice and leptin-deficient obese ob/ob mice
Ueno, N., Inui, A., Kalra, P. S., & Kalra, S. P. (2006) · Peptides · doi:10.1016/j.peptides.2006.03.006 · Cited by 53
Glycyrrhizic Acid and Its Derivatives: Promising Candidates for the Management of Type 2 Diabetes Mellitus and Its Complications
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 55
Coordinated regulation by Shp2 tyrosine phosphatase of signaling events controlling insulin biosynthesis in pancreatic β-cells
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 52

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: Kubota, Naoto
Terauchi, Yasuo
Tobe, Kazuyuki
Yano, Wataru
Suzuki, Ryo
Ueki, Kohjiro
Kubota, Tetsuya
Moroi, Masao
Ezaki, Osamu
Nagai, Ryozo
Ueta, Yoichi
Kadowaki, Takashi
Venue: Journal of Clinical Investigation
Publisher: American Society for Clinical Investigation
Published: 2004-10-01
Volume: 114
Issue: 7
Pages: 917-927
ISSN: 0021-9738 (ISSN-L)
DOI: 10.1172/jci21484
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 › Endocrinology, Diabetes and Metabolism › 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

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

Insulin receptor substrate 2 plays a crucial role in β cells and the hypothalamus

Abstract

Overview

Integrity signals

Verification

Claims the paper makes

Claims other papers make about this one

Self-check

Citations

Cites

Cited by

Related

Metadata

Record

About these checks