Dysregulation of insulin receptor substrate 2 in β cells and brain causes obesity and diabetes
Open accessAbstract
The molecular link between obesity and beta cell failure that causes diabetes is difficult to establish. Here we show that a conditional knockout of insulin receptor substrate 2 (Irs2) in mouse pancreas beta cells and parts of the brain--including the hypothalamus--increased appetite, lean and fat body mass, linear growth, and insulin resistance that progressed to diabetes. Diabetes resolved when the mice were between 6 and 10 months of age: functional beta cells expressing Irs2 repopulated the pancreas, restoring sufficient beta cell function to compensate for insulin resistance in the obese mice. Thus, Irs2 signaling promotes regeneration of adult beta cells and central control of nutrient homeostasis, which can prevent obesity and diabetes in mice.
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
Cites
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?
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 [105]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Central nervous system control of food intake
Schwartz, M. W., Woods, S. C., Porte, D., Seeley, R. J., & Baskin, D. G. (2000) · Nature · doi:10.1038/35007534 · Cited by 6,451 · see citing works
Global and societal implications of the diabetes epidemic
Zimmet, P., Alberti, K. G. M. M., & Shaw, J. (2001) · Nature · doi:10.1038/414782a · Cited by 5,883 · see citing works
Cloning of adiponectin receptors that mediate antidiabetic metabolic effects
Yamauchi, T., Kamon, J., Ito, Y., Tsuchida, A., Yokomizo, T., Kita, S., Sugiyama, T., Miyagishi, M., Hara, K., Tsunoda, M., et al. (2003) · Nature · doi:10.1038/nature01705 · Cited by 3,176 · see citing works
Model-based analysis of oligonucleotide arrays: Expression index computation and outlier detection.
Li, C., & Wong, W. H. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.98.1.31 · Cited by 3,133 · see citing works
A pyramid approach to subpixel registration based on intensity
Thévenaz, P., Ruttimann, U. E., & Unser, M. A. (1998) · IEEE Transactions on Image Processing · doi:10.1109/83.650848 · Cited by 3,097 · see citing works
Targeted disruption of the melanocortin-4 receptor results in obesity in mice
Huszar, D., Lynch, C. A., Fairchild-Huntress, V., Dunmore, J. H., Fang, Q., Berkemeier, L. R., Gu, W., Kesterson, R. A., Boston, B. A., Cone, R. D., et al. (1997) · Cell · doi:10.1016/s0092-8674(00)81865-6 · Cited by 3,030 · 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
The Triumvirate: β-Cell, Muscle, Liver: A Collusion Responsible for NIDDM
DeFronzo, R. A. (1988) · Diabetes · doi:10.2337/diab.37.6.667 · Cited by 2,456 · 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
Adult pancreatic β-cells are formed by self-duplication rather than stem-cell differentiation
Dor, Y., Brown, J., Martinez, O. I., & Melton, D. A. (2004) · Nature · doi:10.1038/nature02520 · Cited by 2,219 · 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
Self-citationClinical Spectrum of Obesity and Mutations in the Melanocortin 4 Receptor Gene
Farooqi, I. S., Keogh, J. M., Yeo, G. S. H., Lank, E. J., Cheetham, T., & O'Rahilly, S. (2003) · New England Journal of Medicine · doi:10.1056/nejmoa022050 · Cited by 1,778 · see citing works
Frederich, R. C., Hamann, A., Anderson, S., Löllmann, B., Lowell, B. B., & Flier, J. S. (1995) · Nature Medicine · doi:10.1038/nm1295-1311 · Cited by 1,660 · see citing works
Postic, C., Shiota, M., Niswender, K. D., Jetton, T. L., Chen, Y., Moates, J. M., Shelton, K. D., Lindner, J., Cherrington, A. D., & Magnuson, M. A. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.1.305 · Cited by 1,302 · see citing works
Zander, M., Madsbad, S., Madsen, J. L., & Holst, J. J. (2002) · The Lancet · doi:10.1016/s0140-6736(02)07952-7 · Cited by 1,297 · see citing works
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 · see citing works
Adiponectin and protection against type 2 diabetes mellitus
Spranger, J., Kroke, A., Möhlig, M., Bergmann, M. M., Ristow, M., Boeing, H., & Pfeiffer, A. F. H. (2003) · The Lancet · doi:10.1016/s0140-6736(03)12255-6 · Cited by 1,120 · see citing works
Chronic intracerebroventricular infusion of insulin reduces food intake and body weight of baboons
Woods, S. C., Lotter, E. C., McKay, L. D., & Porte, D. (1979) · Nature · doi:10.1038/282503a0 · Cited by 1,114 · see citing works
SOCS-1 and SOCS-3 block insulin signaling by ubiquitin-mediated degradation of IRS1 and IRS2
Rui, L., Yuan, M., Frantz, D., Shoelson, S., & White, M. F. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.c200444200 · Cited by 904 · see citing works
Glucagon-like peptide-1 receptor is involved in learning and neuroprotection
During, M. J., Cao, L., Zuzga, D. S., Francis, J. S., Fitzsimons, H. L., Jiao, X., Bland, R. J., Klugmann, M., Banks, W. A., Drucker, D. J., et al. (2003) · Nature Medicine · doi:10.1038/nm919 · Cited by 851 · see citing works
Shimomura, I., Matsuda, M., Hammer, R. E., Bashmakov, Y. K., Brown, M. S., & Goldstein, J. L. (2000) · Molecular Cell · doi:10.1016/s1097-2765(05)00010-9 · Cited by 847 · see citing works
Adiponectin acts in the brain to decrease body weight
Qi, Y., Takahashi, N., Hileman, S. M., Patel, H. R., Berg, A. H., Pajvani, U. B., Scherer, P. E., & Ahima, R. S. (2004) · Nature Medicine · doi:10.1038/nm1029 · Cited by 809 · see citing works
Insulin in the Brain: A Hormonal Regulator of Energy Balance*
Schwartz, M. W., Figlewicz, D. P., Baskin, D. G., Woods, S. C., & Porte, D. (1992) · Endocrine Reviews · doi:10.1210/edrv-13-3-387 · Cited by 808 · see citing works
Tissue-specific overexpression of lipoprotein lipase causes tissue-specific insulin resistance
Kim, J. K., Fillmore, J. J., Chen, Y., Yu, C., Moore, I. K., Pypaert, M., Lutz, E. P., Kako, Y., Velez-Carrasco, W., Goldberg, I. J., et al. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.121164498 · Cited by 753 · see citing works
Insulin signaling in health and disease
White, M. F. (2003) · Science · doi:10.1126/science.1092952 · Cited by 733 · cited 20× · see citing works
“Since IRS2 is highly expressed in the hypothalamus, its signaling cascade may be responsible for integrating central control of nutrient homeostasis and appetite regulation with peripheral insulin action and β cell function (9).”
BackgroundInfluentialDecreasing hypothalamic insulin receptors causes hyperphagia and insulin resistance in rats
Obici, S., Feng, Z., Karkanias, G., Baskin, D. G., & Rossetti, L. (2002) · Nature Neuroscience · doi:10.1038/nn0602-861 · Cited by 719 · see citing works
Kitamura, T., Nakae, J., Kitamura, Y., Kido, Y., Biggs, W., Wright, C. V. E., White, M. F., Arden, K. C., & Accili, D. (2002) · Journal of Clinical Investigation · doi:10.1172/jci16857 · Cited by 578 · see citing works
Self-citationDecreasing hypothalamic insulin receptors causes hyperphagia and insulin resistance in rats
Obici, S., Feng, Z., Karkanias, G. B., et al. (2002) · Nature Neuroscience · doi:10.1038/nn861 · Cited by 572 · 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
Combs, T. P., Berg, A. H., Rajala, M. W., Klebanov, S., Iyengar, P., Jimenez-Chillaron, J. C., Patti, M. E., Klein, S. L., Weinstein, R. S., & Scherer, P. E. (2003) · Diabetes · doi:10.2337/diabetes.52.2.268 · Cited by 544 · see citing works
cAMP promotes pancreatic β-cell survival via CREB-mediated induction of IRS2Preprint
Jhala, U. S., Canettieri, G., Screaton, R. A., Kulkarni, R., Krajewski, S., Reed, J. C., Walker, J. R., Lin, X., White, M. F., & Montminy, M. (2003) · Genes & Development · doi:10.1101/gad.1097103 · Cited by 544 · see citing works
Self-citationBrubaker, P. L., & Drucker, D. J. (2004) · Endocrinology · doi:10.1210/en.2004-0015 · Cited by 539 · 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
Self-citationInsulin Receptor Substrate-2 Deficiency Impairs Brain Growth and Promotes Tau Phosphorylation
Schubert, M., Brazil, D. P., Burks, D. J., Kushner, J. A., Ye, J., Flint, C. L., Farhang-Fallah, J., Dikkes, P., Warot, X. M., Rio, C., et al. (2003) · The Journal of Neuroscience · doi:10.1523/jneurosci.23-18-07084.2003 · Cited by 488 · see citing works
Self-citationDiamond, J. M. (2003) · Nature · doi:10.1038/423599a · Cited by 483 · see citing works
Kitamura, T., Nakae, J., Kitamura, Y., et al. (2002) · Journal of Clinical Investigation · doi:10.1172/jci200216857 · Cited by 479 · see citing works
Insulin Activation of Phosphatidylinositol 3-Kinase in the Hypothalamic Arcuate Nucleus
Niswender, K. D., Morrison, C. D., Clegg, D. J., Olson, R., Baskin, D. G., Myers, M. G., Seeley, R. J., & Schwartz, M. W. (2003) · Diabetes · doi:10.2337/diabetes.52.2.227 · Cited by 476 · see citing works
Leptin Receptor Signaling and the Regulation of Mammalian Physiology
Myers, M. G. (2004) · Recent Progress in Hormone Research · doi:10.1210/rp.59.1.287 · Cited by 458 · see citing works
IRS-2 pathways integrate female reproduction and energy homeostasis
Burks, D. J., de Mora, J. F., Schubert, M., Withers, D. J., Myers, M. G., Towery, H. H., Altamuro, S. L., Flint, C. L., & White, M. F. (2000) · Nature · doi:10.1038/35030105 · Cited by 455 · see citing works
Self-citationCentral melanocortin receptors regulate insulin action
Obici, S., Feng, Z., Tan, J., Liu, L., Karkanias, G. B., & Rossetti, L. (2001) · Journal of Clinical Investigation · doi:10.1172/jci12954 · Cited by 370 · see citing works
Central melanocortin receptors regulate insulin action
Obici, S., Feng, Z., Tan, J., Liu, L., Karkanias, G., & Rossetti, L. (2001) · Journal of Clinical Investigation · doi:10.1172/jci200112954 · Cited by 370 · 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
Model for the regulation of energy balance and adiposity by the central nervous system
Schwartz, M. W., Baskin, D. G., Kaiyala, K. J., & Woods, S. C. (1999) · American Journal of Clinical Nutrition · doi:10.1093/ajcn/69.4.584 · Cited by 323 · see citing works
Nagy, T. R., & Clair, A. (2000) · Obesity Research · doi:10.1038/oby.2000.47 · Cited by 293 · see citing works
Previs, S. F., Withers, D. J., Ren, J.-M., White, M. F., & Shulman, G. I. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.m006490200 · Cited by 291 · see citing works
Self-citationChallis, B. (2002) · Human Molecular Genetics · doi:10.1093/hmg/11.17.1997 · Cited by 288 · see citing works
Non-injection methods for the production of embryonic stem cell-embryo chimaeras
Wood, S. A., Allen, N., Rossant, J., Auerbach, A. B., & Nagy, A. (1993) · Nature · doi:10.1038/365087a0 · Cited by 276 · see citing works
Upregulation of insulin receptor substrate-2 in pancreatic β cells prevents diabetes
Hennige, A. M., Burks, D. J., Özcan, U., Kulkarni, R., Ye, J., Park, S., Schubert, M., Fisher, T. L., Dow, M. A., Leshan, R. L., et al. (2003) · Journal of Clinical Investigation · doi:10.1172/jci18581 · Cited by 260 · see citing works
Self-citationInsulin in the brain: a hormonal regulator of energy balance
Schwartz, M. W. (1992) · Endocrine Reviews · doi:10.1210/er.13.3.387 · Cited by 201 · 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
Self-citationCaMKII?-cre transgene expression and recombination patterns in the mouse brain
Dragatsis, I., & Zeitlin, S. O. (2000) · genesis · doi:10.1002/(sici)1526-968x(200002)26:2 · Cited by 171 · 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
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
Knockout Studies Defining Different Roles for Melanocortin Receptors in Energy Homeostasis
Butler, A. A., & Cone, R. D. (2003) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2003.tb03186.x · Cited by 107 · see citing works
Ehrmann, D. A., Tang, X. A., Yoshiuchi, I., Cox, N. J., & Bell, G. I. (2002) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2002-020216 · Cited by 99 · see citing works
Kushner, J. A., Haj, F. G., Klaman, L. D., et al. (2004) · Diabetes · doi:10.2337/diabetes.53.1.61 · Cited by 69 · see citing works
Self-citationLautier, C., Ait-El-Mkadem, S., Renard, É., et al. (2003) · Human Genetics · doi:10.1007/s00439-003-0935-3 · Cited by 68 · see citing works
Who are more insulin resistant, people with IFG or people with IGT?
Wasada, T., Kuroki, H., Katsumori, K., Arii, H., Sato, A., Aoki, K., Jimba, S., & Hanai, G. (2004) · Diabetologia · doi:10.1007/s00125-004-1339-1 · Cited by 55 · see citing works
Progress in the search for neuronal mechanisms coupling type 2 diabetes to obesity
Schwartz, M. W. (2001) · Journal of Clinical Investigation · doi:10.1172/jci14127 · Cited by 40 · see citing works
Progress in the search for neuronal mechanisms coupling type 2 diabetes to obesity
Schwartz, M. W. (2001) · Journal of Clinical Investigation · doi:10.1172/jci200114127 · Cited by 34 · see citing works
Pdx1 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
Ling, Z., Heimberg, H., Foriers, A., et al. (1998) · Endocrinology · doi:10.1210/endo.139.2.5749 · Cited by 22 · see citing works
Upregulation of insulin receptor substrate-2 in pancreatic β cells prevents diabetes
Hennige, A. M., Burks, D. J., Özcan, U., et al. (2003) · Journal of Clinical Investigation · doi:10.1172/jci200318581 · Cited by 15 · see citing works
The Gly1057Asp polymorphism in IRS-2 interacts with obesity to affect beta cell function
Stefan, N., Fritsche, A., Machicao, F. E., Tschritter, O., H�ring, H. U., & Stümvoll, M. (2004) · Diabetologia · doi:10.1007/s00125-003-1302-6 · Cited by 13 · 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/jci200214439 · Cited by 9 · see citing works
Self-citationLing, Z. (1998) · Endocrinology · doi:10.1210/en.139.2.491 · Cited by 6 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
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
Brain IRS2 Signaling Coordinates Life Span and Nutrient Homeostasis
Taguchi, A., Wartschow, L. M., & White, M. F. (2007) · Science · doi:10.1126/science.1142179 · Cited by 523 · see citing works
Self-citationDong, X. C., Copps, K. D., Guo, S., Li, Y., Kollipara, R., DePinho, R. A., & White, M. F. (2008) · Cell Metabolism · doi:10.1016/j.cmet.2008.06.006 · Cited by 463 · see citing works
Self-citationVery 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
Self-citationCurrent views on type 2 diabetes
Lin, Y., & Sun, Z. (2010) · Journal of Endocrinology · doi:10.1677/joe-09-0260 · Cited by 457 · 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).”
BackgroundCyclins D2 and D1 Are Essential for Postnatal Pancreatic β-Cell Growth
Kushner, J. A., Ciemerych, M. A., Sicinska, E., Wartschow, L. M., Teta, M., Long, S. Y., Sicinski, P., & White, M. F. (2005) · Molecular and Cellular Biology · doi:10.1128/mcb.25.9.3752-3762.2005 · Cited by 334 · see citing works
Self-citationMorton, 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
Genetic inactivation of p62 leads to accumulation of hyperphosphorylated tau and neurodegeneration
Ramesh Babu, J., Lamar Seibenhener, M., Peng, J., Strom, A., Kemppainen, R., Cox, N., Zhu, H., Wooten, M. C., Diaz‐Meco, M. T., Moscat, J., et al. (2008) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2008.05340.x · Cited by 258 · see citing works
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 · see citing works
Brain regulation of energy balance and body weight
Rui, L. (2013) · Reviews in Endocrine and Metabolic Disorders · doi:10.1007/s11154-013-9261-9 · Cited by 168 · 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
Obese men respond to cognitive but not to catabolic brain insulin signaling
Hallschmid, M., Benedict, C., Schultes, B., Born, J., & Kern, W. (2008) · International Journal of Obesity · doi:10.1038/sj.ijo.0803722 · Cited by 165 · see citing works
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 · see citing works
Insulin receptor substrate signaling suppresses neonatal autophagy in the heart
Riehle, C., Wende, A. R., Sena, S., Pires, K. M., Pereira, R. O., Zhu, Y., Bugger, H., Frank, D., Bevins, J., Chen, D., et al. (2013) · Journal of Clinical Investigation · doi:10.1172/jci71171 · Cited by 114 · see citing works
Self-citationIRS2 increases mitochondrial dysfunction and oxidative stress in a mouse model of Huntington disease
Sadagurski, M., Cheng, Z., Rozzo, A., Palazzolo, I., Kelley, G. R., Dong, X., Krainc, D., & White, M. F. (2011) · Journal of Clinical Investigation · doi:10.1172/jci46305 · Cited by 107 · see citing works
Self-citationThe pathophysiology of defective proteostasis in the hypothalamus — from obesity to ageing
Cavadas, C., Aveleira, C. A., Souza, G. F. P., & Velloso, L. A. (2016) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2016.107 · Cited by 105 · see citing works
Riehle, C., Wende, A. R., Zhu, Y., Oliveira, K. J., Pereira, R. O., Jaishy, B. P., Bevins, J., Valdez, S., Noh, J., Kim, B. J., et al. (2014) · Molecular and Cellular Biology · doi:10.1128/mcb.00426-14 · Cited by 105 · see citing works
Self-citationβ‐cell mass in people with type 2 diabetes
Cho, J., Kim, J., Shin, J., Shin, J., & Yoon, K. (2011) · Journal of Diabetes Investigation · doi:10.1111/j.2040-1124.2010.00072.x · Cited by 69 · see citing works
Control of metabolic and cardiovascular function by the leptin–brain melanocortin pathway
do Carmo, J. M., da Silva, A. A., Dubinion, J., Sessums, P. O., Ebaady, S. H., Wang, Z., & Hall, J. E. (2013) · IUBMB Life · doi:10.1002/iub.1187 · Cited by 36 · see citing works
The Brain-Gut-Islet Connection
Woods, S. C., Benoit, S. C., & Clegg, D. J. (2006) · Diabetes · doi:10.2337/db06-s015 · Cited by 30 · see citing works
- Authors
- Lin, X., Taguchi, A., Park, S., Kushner, J. A., Li, F., Li, Y., & White, M. F.
- Affiliations
- Howard Hughes Medical Institute (US)
- Corresponding author
- White, Morris F.
- Venue
- Journal of Clinical Investigation
- Published
- 2004-10-01
- Volume
- 114
- Issue
- 7
- Pages
- 908-916
- ISSN
- 0021-9738 (ISSN-L)
- PMC
- PMC518668
- OpenAlex
- W1966373813
- Cited by
- 313
- References
- 66
- Citations by year
- 2026: 5 · 2025: 7 · 2024: 8 · 2023: 2 · 2022: 7 · 2021: 11 · 2020: 11 · 2019: 10 · 2018: 8 · 2017: 10 · 2016: 13 · 2015: 22 · 2014: 16 · 2013: 17 · 2012: 14
- FWCI
- 21.86
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Investigation (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Institute of Diabetes and Digestive and Kidney Diseases (DK55236)
- Topics
- Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Diabetes and associated disorders
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Keywords
- insulin receptor substrate 2, pancreatic beta cells, hypothalamus, obesity, diabetes mellitus, insulin resistance, beta cell regeneration, appetite, nutrient homeostasis, conditional knockout
- MeSH terms
- Animals, Body Weight, Brain, Diabetes Mellitus, Type 2, Diet, Eating, Gene Expression Regulation, Glucose, Homeostasis, Humans, Hypothalamus, Insulin, Insulin Resistance, Islets of Langerhans, Male, Mice, Inbred C57BL, Obesity, Phosphoproteins, Random Allocation, Signal Transduction, Gene Deletion, Mice, Knockout, 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
