The DOI matches its Crossref record; 253 of the 255 references it cites were found in a registry or an index.
Brain insulin signalling in metabolic homeostasis and disease
Abstract
Insulin signalling in the central nervous system regulates energy homeostasis by controlling metabolism in several organs and by coordinating organ crosstalk. Studies performed in rodents, non-human primates and humans over more than five decades using intracerebroventricular, direct hypothalamic or intranasal application of insulin provide evidence that brain insulin action might reduce food intake and, more importantly, regulates energy homeostasis by orchestrating nutrient partitioning. This Review discusses the metabolic pathways that are under the control of brain insulin action and explains how brain insulin resistance contributes to metabolic disease in obesity, the metabolic syndrome and type 2 diabetes mellitus.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
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?
In the citing paper
“Over the last decade, the brain was characterized as an insulin-sensitive organ1.”
From Brain insulin action on peripheral insulin sensitivity in women depends on menstrual cycle phase (2023) · cites this paper as [1]
In the citing paper
“Insulin action in the human brain modulates eating behaviour, whole-body metabolism and body fat distribution1,2.”
From Brain insulin action on peripheral insulin sensitivity in women depends on menstrual cycle phase (2023) · cites this paper as [1]
In the citing paper
“acts in specialized neurons and glia cells1”
From Brain insulin action on peripheral insulin sensitivity in women depends on menstrual cycle phase (2023) · cites this paper as [1]
In the citing paper
“The most prominent phenotype linked to human brain insulin resistance is obesity1”
From Brain insulin action on peripheral insulin sensitivity in women depends on menstrual cycle phase (2023) · cites this paper as [1]
In the citing paper
“Insulin receptors are highly expressed in the brain, not only in the hypothalamus, olfactory bulb, hippocampus, and striatum, but also in cerebral cortex, and cerebellum.175”
From The blood–brain barrier: Structure, regulation and drug delivery (2023) · cites this paper as [175]
Citations
Cites
Items 201–253 of 253
Central Endocannabinoid Signaling Regulates Hepatic Glucose Production and Systemic Lipolysis
O’Hare, J., Zieliński, E., Cheng, B., Scherer, T., & Buettner, C. (2011) · Diabetes · doi:10.2337/db10-0962 · Cited by 58
Self-citationFadel, J. R., & Reagan, L. P. (2015) · Current Opinion in Behavioral Sciences · doi:10.1016/j.cobeha.2015.12.004 · Cited by 58
Ramnanan, C. J., Edgerton, D. S., & Cherrington, A. D. (2012) · Cell Metabolism · doi:10.1016/j.cmet.2012.03.006 · Cited by 56
Akintola, A. A., van Opstal, A. M., Westendorp, R. G. J., Postmus, I., van der Grond, J., & van Heemst, D. (2017) · Aging · doi:10.18632/aging.101192 · Cited by 56
Insulin, Synaptic Function, and Opportunities for Neuroprotection
Mielke, J. G., & Wang, Y.-T. (2011) · Progress in Molecular Biology and Translational Science · doi:10.1016/b978-0-12-385506-0.00004-1 · Cited by 55
Modulation of midbrain neurocircuitry by intranasal insulin
Edwin Thanarajah, S., Iglesias, S., Kuzmanovic, B., Rigoux, L., Stephan, K. E., Brüning, J. C., & Tittgemeyer, M. (2019) · NeuroImage · doi:10.1016/j.neuroimage.2019.03.050 · Cited by 55
Florant, G. L., Singer, L. K., Scheurink, A. J. W., Park, C. R., Richardson, R. D., & Woods, S. C. (1991) · Physiology & Behavior · doi:10.1016/0031-9384(91)90053-q · Cited by 54
Dornhorst, A., Lüddeke, H. ‐., Koenen, C., Merilainen, M. J., King, A. B., Robinson, A., Sreenan, S., & PREDICTIVE Study Group (2007) · Diabetes Obesity and Metabolism · doi:10.1111/j.1463-1326.2007.00816.x · Cited by 54
STAT3 Sensitizes Insulin Signaling by Negatively Regulating Glycogen Synthase Kinase-3β
Moh, A., Zhang, W., Yu, S. S. B., Wang, J., Xu, X., Li, J., & Fu, X.-Y. (2008) · Diabetes · doi:10.2337/db06-1582 · Cited by 53
Cerebrocortical Beta Activity in Overweight Humans Responds to Insulin Detemir
Tschritter, O., Hennige, A. M., Preissl, H. T., Porubská, K., Schäfer, S., Lutzenberger, W., Machicao, F. E., Birbaumer, N., Fritsche, A., & Häring, H. (2007) · PLoS ONE · doi:10.1371/journal.pone.0001196 · Cited by 52
Li, J. H., Gautam, D., Han, S., Guettier, J., Cui, Y., Lü, H., Deng, C., O’Hare, J., Jou, W., Gavrilova, O., et al. (2009) · Diabetes · doi:10.2337/db09-0522 · Cited by 52
Self-citationThe effects of short-term overfeeding on insulin action in lean and reduced-obese individuals
Cornier, M., Bergman, B. C., & Bessesen, D. H. (2006) · Metabolism · doi:10.1016/j.metabol.2006.05.003 · Cited by 51
van der Crabben, S. N., Allick, G., Ackermans, M. T., Endert, E., Romijn, J. A., & Sauerwein, H. P. (2007) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2006-2491 · Cited by 50
Metabolic effects of liver transplantation in cirrhotic patients.
Luzi, L., Perseghin, G., Regalia, E., Sereni, L. P., Battezzati, A., Baratti, D., Bianchi, E., Terruzzi, I., Hilden, H., Groop, L., et al. (1997) · Journal of Clinical Investigation · doi:10.1172/jci119213 · Cited by 50
Hallschmid, M., Schultes, B., Marshall, L., Mölle, M., Kern, W., Bredthauer, J., Fehm, H. L., & Jan Born, A. (2004) · Diabetes · doi:10.2337/diabetes.53.9.2202 · Cited by 50
Feeding-related immunoreactive insulin changes in the PVN-VMH revealed by microdialysis
Orosco, M., Gerozissis, K., Rouch, C., & Nicolaı̈dis, S. (1995) · Brain Research · doi:10.1016/0006-8993(94)01347-k · Cited by 49
Inverse relation between FASN expression in human adipose tissue and the insulin resistance level
Mayas, M., Ortega, F., Macías-González, M., Bernal, R., Gómez-Huelgas, R., Fernández-Real, J., & Tinahones, F. (2010) · Nutrition and Metabolism · doi:10.1186/1743-7075-7-3 · Cited by 49
Cashion, M. F., Banks, W. A., & Kastin, A. J. (1996) · Hormones and Behavior · doi:10.1006/hbeh.1996.0034 · Cited by 47
Yue, J. T. Y., Abraham, M. A., LaPierre, M. P., Mighiu, P. I., Light, P. E., Filippi, B. M., & Lam, T. K. T. (2015) · Nature Communications · doi:10.1038/ncomms6970 · Cited by 46
Insulin-like Growth Factor 1-mediated Hyperthermia Involves Anterior Hypothalamic Insulin Receptors
Sánchez-Alavez, M., Osborn, O., Tabarean, I. V., Holmberg, K. H., Eberwine, J. H., Kahn, C. R., & Bartfai, T. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.188540 · Cited by 44
Insulin Modulation of Magnetoencephalographic Resting State Dynamics in Lean and Obese Subjects
Stingl, K. T., Kullmann, S., Guthoff, M., Heni, M., Fritsche, A., & Preissl, H. T. (2010) · Frontiers in Systems Neuroscience · doi:10.3389/fnsys.2010.00157 · Cited by 41
Diet-induced thermogenesis: fake friend or foe?
Ho, K. K. Y. (2018) · Journal of Endocrinology · doi:10.1530/joe-18-0240 · Cited by 41
Shrestha, Y. B., Vaughan, C. H., Smith, B. J., Song, C. K., Baro, D. J., & Bartness, T. J. (2010) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00535.2009 · Cited by 40
Inconsistencies in the assessment of food intake
Woods, S. C., & Langhans, W. (2012) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00415.2012 · Cited by 39
Farmer, T. D., Jenkins, E. C., O’Brien, T. P., McCoy, G. A., Havlik, A. E., Nass, E. R., Nicholson, W. E., Printz, R. L., & Shiota, M. (2014) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00406.2014 · Cited by 39
Ott, V., Lehnert, H., Staub, J., Wönne, K., Jan Born, A., & Hallschmid, M. (2014) · Diabetes · doi:10.2337/db14-0931 · Cited by 36
Activation of Brain Somatostatin Signaling Suppresses CRF Receptor-Mediated Stress Response
Stengel, A., & Taché, Y. (2017) · Frontiers in Neuroscience · doi:10.3389/fnins.2017.00231 · Cited by 36
How Can a Good Idea Fail? Basal Insulin Peglispro [LY2605541] for the Treatment of Type 2 Diabetes
Muñoz‐Garach, A., Molina‐Vega, M., & Tinahones, F. J. (2016) · Diabetes Therapy · doi:10.1007/s13300-016-0214-7 · Cited by 34
Ketterer, C., Heni, M., Stingl, K. T., Tschritter, O., Linder, K., Wagner, R. J., Machicao, F. E., Häring, H., Preissl, H. T., Staiger, H., et al. (2013) · Obesity · doi:10.1002/oby.20573 · Cited by 31
Begg, D. P., May-Zhang, A. A., Mul, J. D., Liu, M., D’Alessio, D. A., Seeley, R. J., & Woods, S. C. (2015) · Diabetes · doi:10.2337/db14-1364 · Cited by 31
The role of endoplasmic reticulum stress in hippocampal insulin resistance
Sims‐Robinson, C., Bakeman, A., Glasser, R., Boggs, J. M., Pacut, C. M., & Feldman, E. L. (2016) · Experimental Neurology · doi:10.1016/j.expneurol.2016.01.007 · Cited by 30
Cerebrospinal fluid insulin during non-neurological surgery
Bromander, S., Anckarsäter, R., Åhrén, B., Kristiansson, M., Blennow, K., Holmäng, A. B., Zetterberg, H., Anckarsäter, H. S., & Wass, C. (2010) · Journal of Neural Transmission · doi:10.1007/s00702-010-0456-x · Cited by 29
Evaluation of the lack of anorectic effect of intracerebroventricular insulin in rats
Jessen, L., Clegg, D. J., & Bouman, S. D. (2010) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.90736.2008 · Cited by 29
Kameyama, M., Murakami, K., & Jinzaki, M. (2016) · World Journal of Nuclear Medicine · doi:10.4103/1450-1147.172139 · Cited by 28
Coomans, C. P., Geerling, J. J., Guigas, B., van den Hoek, A. M., Parlevliet, E. T., Ouwens, D. M., Pijl, H., Voshol, P. J., Rensen, P. C. N., Havekes, L. M., et al. (2011) · Journal of Lipid Research · doi:10.1194/jlr.m015396 · Cited by 26
Ancient oncogenesis, infection and human evolution
Rifkin, R. F., Potgieter, M., Ramond, J., & Cowan, D. A. (2017) · Evolutionary Applications · doi:10.1111/eva.12497 · Cited by 26
Ajaya, B., & Ps, H. (1982) · PubMed · Cited by 23
Gancheva, S., Bierwagen, A., Markgraf, D. F., Bönhof, G. J., Murphy, K. G., Hatziagelaki, E. E., Lundbom, J., Ziegler, D., & Roden, M. (2017) · Molecular Metabolism · doi:10.1016/j.molmet.2017.10.002 · Cited by 23
A Hypothalamic Phosphatase Switch Coordinates Energy Expenditure with Feeding
Dodd, G. T., Andrews, Z. B., Simonds, S. E., Michael, N. J., DeVeer, M., Brüning, J. C., Spanswick, D. C., Cowley, M. A., & Tiganis, T. (2017) · Cell Metabolism · doi:10.1016/j.cmet.2017.08.001 · Cited by 22
Waldhäusl, W. K., Bratusch-Marrain, P. R., Francesconi, M., Nowotny, P., & Kiss, A. (1982) · Diabetes Care · doi:10.2337/diacare.5.1.18 · Cited by 21
Lin, H. V., & Accili, D. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.210807 · Cited by 19
Is Brain Insulin Action Relevant to the Control of Plasma Glucose in Humans?
Edgerton, D. S., & Cherrington, A. D. (2015) · Diabetes · doi:10.2337/db14-1666 · Cited by 18
Deletion of the insulin receptor in sensory neurons increases pancreatic insulin levels
Grote, C. W., Wilson, N. M., Katz, N. K., Guilford, B. L., Ryals, J. M., Novikova, L., Stehno‐Bittel, L., & Wright, D. E. (2018) · Experimental Neurology · doi:10.1016/j.expneurol.2018.04.002 · Cited by 18
POSTPRANDIAL HEPATIC GLYCOGEN SYNTHESIS IN LIVER TRANSPLANT RECIPIENTS1
Schneiter, P., Gillet, M., ro, R. C., Wauters, J., Berger, M. M., & Tappy, L. (2000) · Transplantation · doi:10.1097/00007890-200003150-00052 · Cited by 17
Müller, C., Voirol, M.-J., Stefanoni, N., Surmely, J., Jéquier, E., Gaillard, R., & Tappy, L. (1997) · International Journal of Obesity · doi:10.1038/sj.ijo.0800441 · Cited by 17
Scherer, T., Wolf, P. S., Smajis, S., Gaggini, M., Hackl, M. T., Gastaldelli, A., Klimek, P., Einwallner, E., Marculescu, R., Luger, A., et al. (2017) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2016-3623 · Cited by 17
Self-citationEffects of Intranasal Insulin on Triglyceride-Rich Lipoprotein Particle Production in Healthy Men
Xiao, C., Dash, S., Stahel, P., & Lewis, G. F. (2017) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.117.309705 · Cited by 16
Plomgaard, P., Hansen, J. S., Ingerslev, B., Clemmesen, J. O., Secher, N. H., van Hall, G., Fritsche, A., Weigert, C., Lehmann, R., Häring, H., et al. (2019) · Diabetes, Obesity and Metabolism · doi:10.1111/dom.13615 · Cited by 16
Vella, A. V., Sathananthan, M., Ikramuddin, S., Swain, J. M., Shah, M., Piccinini, F., Man, C. D., Cobelli, C., Rizza, R. A., & Camilleri, M. (2014) · Diabetes Metabolic Syndrome and Obesity · doi:10.2147/dmso.s65733 · Cited by 15
Grunberger, G., Chen, L., Rodríguez, Á., Tinahones, F. J., Jacober, S. J., Bue‐Valleskey, J. M., & on behalf of the IMAGINE 6 Investigators (2016) · Diabetes Obesity and Metabolism · doi:10.1111/dom.12743 · Cited by 13
Continence promotion. My three D's.
Blannin, J. (1986) · PubMed · Cited by 4
Mechanism of amygdaloid convulsive seizure development.
Wada, J. A. (1982) · PubMed · Cited by 4
Lithium in psychiatry: reply to discussants.
Rr, F. (1971) · PubMed · Cited by 1
Research works printed but not linked: 1
- Blinkow, S. & Glezer, I. in The Human Brain in Figures and Tables (ed. Blinkow, F. G.) 237–253 (Plenum Press, 1968).
Cited by
Sorted by citations
The blood–brain barrier: Structure, regulation and drug delivery
Wu, D., Chen, Q., Chen, X., Han, F., Chen, Z., & Wang, Y. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01481-w · Cited by 1,906
“175 Insulin could bind to the α -subunits of insulin receptors which locate outside of the cells, inducing the β -subunits which locate in the inside of the cells 176 When compared to insulin, insulin-like growth factor 1 (IGF1) showed relative lower binding af fi nity to insulin receptors.”
BackgroundDewanjee, S., Chakraborty, P., Bhattacharya, H., Chacko, L., Singh, B., Chaudhary, A., Javvaji, K., Pradhan, S. R., Vallamkondu, J., Dey, A., et al. (2022) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2022.09.032 · Cited by 243
Lima, J. E. B. F., Moreira, N. C. S., & Sakamoto-Hojo, E. T. (2022) · Mutation Research/Genetic Toxicology and Environmental Mutagenesis · doi:10.1016/j.mrgentox.2021.503437 · Cited by 203
Insulin resistance in depression: A large meta-analysis of metabolic parameters and variation
Fernandes, B. S., Salagre, E., Enduru, N., Grande, I., Vieta, E., & Zhao, Z. (2022) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2022.104758 · Cited by 175
Insulin resistance in ischemic stroke: Mechanisms and therapeutic approaches
Ding, P.-F., Zhang, H., Wang, J., Gao, Y., Mao, J.-N., Hang, C., & Li, W. (2022) · Frontiers in Endocrinology · doi:10.3389/fendo.2022.1092431 · Cited by 143
Metadata
- Authors
- Scherer, T., Sakamoto, K., & Buettner, C.
- Affiliations
- Medical University of Vienna (AT)
- Rutgers, The State University of New Jersey (US)
- Corresponding author
- Scherer, Thomas
- Buettner, Christoph
- Venue
- Nature Reviews Endocrinology
- Published
- 2021-06-09
- Volume
- 17
- Issue
- 8
- Pages
- 468-483
- ISSN
- 1759-5029 (ISSN-L)
- 1759-5037
- OpenAlex
- W3167467420
- Cited by
- 205
- References
- 255
- Citations by year
- 2026: 38 · 2025: 36 · 2024: 61 · 2023: 35 · 2022: 30 · 2021: 5
- FWCI
- 4.15
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Nature Reviews Endocrinology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adipokines, Inflammation, and Metabolic Diseases
- Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
- Keywords
- insulin resistance, energy homeostasis, nutrient partitioning, food intake regulation, obesity, metabolic syndrome, type 2 diabetes, hypothalamus, intranasal insulin, organ crosstalk, metabolic disease treatment
- MeSH terms
- Animals, Brain, Diabetes Mellitus, Type 2, Energy Metabolism, Homeostasis, Humans, Insulin, Insulin Resistance, Metabolic Diseases, Signal Transduction, Metabolic Syndrome
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
