Cited by 245Regulation of Appetite and ObesityAdipokines, Inflammation, and Metabolic DiseasesDiabetes, Cardiovascular Risks, and Lipoproteins

The DOI matches its Crossref record; 158 of the 158 references it cites were found in a registry or an index.

Impaired insulin action in the human brain: causes and metabolic consequences

Heni, Martin, Kullmann, Stephanie, Preissl, Hubert, Fritsche, Andreas, Häring, Hans-Ulrich·2015·Nature Reviews Endocrinology

DOI 10.1038/nrendo.2015.173

Open this paper in CoChat — free account

Abstract

Over the past few years, evidence has accumulated that the human brain is an insulin-sensitive organ. Insulin regulates activity in a limited number of specific brain areas that are important for memory, reward, eating behaviour and the regulation of whole-body metabolism. Accordingly, insulin in the brain modulates cognition, food intake and body weight as well as whole-body glucose, energy and lipid metabolism. However, brain imaging studies have revealed that not everybody responds equally to insulin and that a substantial number of people are brain insulin resistant. In this Review, we provide an overview of the effects of insulin in the brain in humans and the relevance of the effects for physiology. We present emerging evidence for insulin resistance of the human brain. Factors associated with brain insulin resistance such as obesity and increasing age, as well as possible pathogenic factors such as visceral fat, saturated fatty acids, alterations at the blood-brain barrier and certain genetic polymorphisms, are reviewed. In particular, the metabolic consequences of brain insulin resistance are discussed and possible future approaches to overcome brain insulin resistance and thereby prevent or treat obesity and type 2 diabetes mellitus are outlined.

Integrity signals

Registry

Crossref · 10.1038/nrendo.2015.173

Cites

158 of 158 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

This paper’s full text isn’t openly available, so its claims and self-check weren’t run. The registry and citation checks still apply.

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?

Homeostasis model assessment: insulin resistance and ?-cell function from fasting plasma glucose and insulin concentrations in man
Matthews, D. R., Hosker, J. P., Rudenski, A. S., Naylor, B. A., Treacher, D. F., & Turner, R. C. (1985) · Diabetologia · doi:10.1007/bf00280883 · Cited by 31,502
Magnesium Replacement Improves the Metabolic Profile in Obese and Pre-Diabetic Patients with Mild-to-Moderate Chronic Kidney Disease: A 3-Month, Randomised, Double-Blind, Placebo-Controlled Study
Toprak, Ö., Kurt, H., Sarı, Y., Şarkış, C., Us, H., & Kırık, A. (2017) · Kidney & Blood Pressure Research · doi:10.1159/000468530 · Cited by 29,772
Genetics of Food Intake Self-Regulation in Childhood: Literature Review and Research Opportunities
Faith, M. S., Carnell, S., & Kral, T. V. E. (2013) · Human Heredity · doi:10.1159/000353879 · Cited by 7,633
Impact of Informing Overweight Individuals about the Role of Genetics in Obesity: An Online Experimental Study
Lippa, N. C., & Sanderson, S. C. (2013) · Human Heredity · doi:10.1159/000353712 · Cited by 6,095
Use and Abuse of HOMA Modeling
Wallace, T. M., Levy, J. C., & Matthews, D. R. (2004) · Diabetes Care · doi:10.2337/diacare.27.6.1487 · Cited by 5,114
A Common Variant in the FTO Gene Is Associated with Body Mass Index and Predisposes to Childhood and Adult Obesity
Frayling, T. M., Timpson, N. J., Weedon, M. N., Zeggini, E., Freathy, R. M., Lindgren, C. M., Perry, J. R. B., Elliott, K. S., Lango, H., Rayner, N. W., et al. (2007) · Science · doi:10.1126/science.1141634 · Cited by 4,531
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
Central nervous system control of food intake and body weight
Morton, G. J., Cummings, D. E., Baskin, D. G., Barsh, G. S., & Schwartz, M. W. (2006) · Nature · doi:10.1038/nature05026 · Cited by 2,503
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
Role of Fatty Acids in the Pathogenesis of Insulin Resistance and NIDDM
Boden, G. (1997) · Diabetes · doi:10.2337/diab.46.1.3 · Cited by 1,728

Show all 158 references

Sorted by citations

Mechanisms of Insulin Action and Insulin Resistance
Petersen, M. C., & Shulman, G. I. (2018) · Physiological Reviews · doi:10.1152/physrev.00063.2017 · Cited by 3,028
Brain insulin resistance in Alzheimer's disease and related disorders: mechanisms and therapeutic approaches
Kellar, D., & Craft, S. (2020) · The Lancet Neurology · doi:10.1016/s1474-4422(20)30231-3 · Cited by 832
Hypothalamic circuits regulating appetite and energy homeostasis: pathways to obesity
Timper, K., & Brüning, J. C. (2017) · Disease Models & Mechanisms · doi:10.1242/dmm.026609 · Cited by 851
Brain Insulin Resistance at the Crossroads of Metabolic and Cognitive Disorders in Humans
Kullmann, S., Heni, M., Hallschmid, M., Fritsche, A., Preissl, H. T., & Häring, H. (2016) · Physiological Reviews · doi:10.1152/physrev.00032.2015 · Cited by 654
Self-citation
The impact of insulin resistance on the kidney and vasculature
Artunç, F., Schleicher, E. D., Weigert, C., Fritsche, A., Stefan, N., & Häring, H. (2016) · Nature Reviews Nephrology · doi:10.1038/nrneph.2016.145 · Cited by 481
Self-citation
Insulin Signaling and Heart Failure
Riehle, C., & Abel, E. D. (2016) · Circulation Research · doi:10.1161/circresaha.116.306206 · Cited by 420
The Prefrontal Cortex and Obesity: A Health Neuroscience Perspective
Lowe, C. J., Reichelt, A. C., & Hall, P. A. (2019) · Trends in Cognitive Sciences · doi:10.1016/j.tics.2019.01.005 · Cited by 295
Fibroblast Growth Factor 21—Metabolic Role in Mice and Men
Staiger, H., Keuper, M., Berti, L., Hrabě de Angelis, M., & Häring, H.-U. (2017) · Endocrine Reviews · doi:10.1210/er.2017-00016 · Cited by 270
Self-citation
Insulin Resistance and Oxidative Stress in the Brain: What’s New?
Maciejczyk, M., Żebrowska, E., & Chabowski, A. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20040874 · Cited by 293
Weight loss is associated with improvements in cognitive function among overweight and obese people: a systematic review and meta-analysis
Veronese, N., Facchini, S., Stubbs, B., Luchini, C., Solmi, M., Manzato, E., Sergi, G., Maggi, S., Cosco, T., & Fontana, L. (2017) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2016.11.017 · Cited by 251
Insulin Resistance as a Link between Amyloid-Beta and Tau Pathologies in Alzheimer’s Disease
Mullins, R. J., Diehl, T. C., Chia, C. W., & Kapogiannis, D. (2017) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2017.00118 · Cited by 227
Mechanisms underlying the pathophysiology of type 2 diabetes: From risk factors to oxidative stress, metabolic dysfunction, and hyperglycemia
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
Metabolism, Metabolomics, and Inflammation in Posttraumatic Stress Disorder
Mellon, S. H., Gautam, A., Hammamieh, R., Jett, M., & Wolkowitz, O. M. (2018) · Biological Psychiatry · doi:10.1016/j.biopsych.2018.02.007 · Cited by 184
How Does Exercise Reduce the Rate of Age-Associated Cognitive Decline? A Review of Potential Mechanisms
Kennedy, G., Hardman, R. J., Macpherson, H., Scholey, A. B., & Pipingas, A. (2016) · Journal of Alzheimer s Disease · doi:10.3233/jad-160665 · Cited by 199
Age-related hyperinsulinemia leads to insulin resistance in neurons and cell-cycle-induced senescence
Chow, H.-M., Shi, M., Cheng, A., Gao, Y., Chen, G., Song, X., So, R. W. L., Zhang, J., & Herrup, K. (2019) · Nature Neuroscience · doi:10.1038/s41593-019-0505-1 · Cited by 171
The Complex Interactions Between Obesity, Metabolism and the Brain
Uranga, R. M., & Keller, J. N. (2019) · Frontiers in Neuroscience · doi:10.3389/fnins.2019.00513 · Cited by 174
The blood–brain barrier as an endocrine tissue
Banks, W. A. (2019) · Nature Reviews Endocrinology · doi:10.1038/s41574-019-0213-7 · Cited by 168
Review: Traumatic brain injury and hyperglycemia, a potentially modifiable risk factor
Shi, J., Dong, B., Mao, Y., Guan, W., Cao, J., Zhu, R., & Wang, S. (2016) · Oncotarget · doi:10.18632/oncotarget.11958 · Cited by 174
Insulin Receptor Associates with Promoters Genome-wide and Regulates Gene Expression
Hancock, M., Meyer, R. C., Mistry, M., Khetani, R. S., Wagschal, A., Shin, T., Sui, S. J. H., Näär, A. M., & Flanagan, J. G. (2019) · Cell · doi:10.1016/j.cell.2019.02.030 · Cited by 160
Distribution of insulin in trigeminal nerve and brain after intranasal administration
Lochhead, J. J., Kellohen, K. L., Ronaldson, P. T., & Davis, T. P. (2019) · Scientific Reports · doi:10.1038/s41598-019-39191-5 · Cited by 146
Metabolism-Centric Overview of the Pathogenesis of Alzheimer's Disease
Kang, S., Lee, Y., & Lee, J. E. (2017) · Yonsei Medical Journal · doi:10.3349/ymj.2017.58.3.479 · Cited by 148
Brain functional and structural magnetic resonance imaging of obesity and weight loss interventions
Li, G., Hu, Y., Zhang, W., Wang, J., Ji, W., Manza, P., Volkow, N. D., Zhang, Y., & Wang, G. (2023) · Molecular Psychiatry · doi:10.1038/s41380-023-02025-y · Cited by 149
Brain insulin sensitivity is linked to adiposity and body fat distribution
Kullmann, S., Valenta, V., Wagner, R., Tschritter, O., Machann, J., Häring, H.-U., Preissl, H., Fritsche, A., & Heni, M. (2020) · Nature Communications · doi:10.1038/s41467-020-15686-y · Cited by 134
Self-citation
Insulin-degrading enzyme: new therapeutic target for diabetes and Alzheimer’s disease?
Pivovarova‐Ramich, O., Höhn, A., Grune, T., Pfeiffer, A. F. H., & Rudovich, N. N. (2016) · Annals of Medicine · doi:10.1080/07853890.2016.1197416 · Cited by 132
Insulin resistance and clinical outcomes after acute ischemic stroke
Ago, T., Matsuo, R., Hata, J., Wakisaka, Y., Kuroda, J., Kitazono, T., Kamouchi, M., & On behalf of the Fukuoka Stroke Registry Investigators (2018) · Neurology · doi:10.1212/wnl.0000000000005358 · Cited by 135
Resting-state functional connectivity of the human hypothalamus
Kullmann, S., Heni, M., Linder, K., Zipfel, S., Häring, H., Veit, R., Fritsche, A., & Preissl, H. T. (2014) · Human Brain Mapping · doi:10.1002/hbm.22607 · Cited by 127
Self-citation
Molecular mechanisms underlying hyperglycemia associated cognitive decline
Gupta, M., Pandey, S., Rumman, M., Singh, B., & Mahdi, A. A. (2022) · IBRO Neuroscience Reports · doi:10.1016/j.ibneur.2022.12.006 · Cited by 133
Insulin resistance in Alzheimer's disease
Diehl, T. C., Mullins, R. J., & Kapogiannis, D. (2016) · Translational research · doi:10.1016/j.trsl.2016.12.005 · Cited by 124
The Triangle of Death in Alzheimer's Disease Brain: The Aberrant Cross-Talk Among Energy Metabolism, Mammalian Target of Rapamycin Signaling, and Protein Homeostasis Revealed by Redox Proteomics
Di Domenico, F., Barone, E., Perluigi, M., & Butterfield, D. A. (2017) · Antioxidants & Redox Signaling · doi:10.1089/ars.2016.6759 · Cited by 114
Hypothalamic and Striatal Insulin Action Suppresses Endogenous Glucose Production and May Stimulate Glucose Uptake During Hyperinsulinemia in Lean but Not in Overweight Men
Heni, M., Wagner, R., Kullmann, S., Gancheva, S., Roden, M., Peter, A., Stefan, N., Preissl, H., Häring, H.-U., & Fritsche, A. (2017) · Diabetes · doi:10.2337/db16-1380 · Cited by 115
Self-citation
The Relevance of Insulin Action in the Dopaminergic System
Fiory, F., Perruolo, G., Cimmino, I., Cabaro, S., Pignalosa, F. C., Miele, C., Bèguinot, F., Formisano, P., & Oriente, F. (2019) · Frontiers in Neuroscience · doi:10.3389/fnins.2019.00868 · Cited by 118
Central insulin modulates food valuation via mesolimbic pathways
Tiedemann, L. J., Schmid, S. M., Hettel, J., Giesen, K., Francke, P., Büchel, C., & Brassen, S. (2017) · Nature Communications · doi:10.1038/ncomms16052 · Cited by 113
Cerebrovascular insulin receptors are defective in Alzheimer’s disease
Leclerc, M., Bourassa, P., Tremblay, C., Caron, V., Sugère, C., Émond, V., Bennett, D. A., & Calon, F. (2022) · Brain · doi:10.1093/brain/awac309 · Cited by 113
Safety of intranasal human insulin: A review
Schmid, V., Kullmann, S., Gfrörer, W., Hund, V., Hallschmid, M., Lipp, H., Häring, H., Preissl, H., Fritsche, A., & Heni, M. (2018) · Diabetes, Obesity and Metabolism · doi:10.1111/dom.13279 · Cited by 110
Self-citation
Long-term exposition to a high fat diet favors the appearance of β-amyloid depositions in the brain of C57BL/6J mice. A potential model of sporadic Alzheimer’s disease
Busquets, O., Ettcheto, M., Pallàs, M., Beas‐Zárate, C., Verdaguer, E., Auladell, C., Folch, J., & Camins, A. (2016) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2016.11.002 · Cited by 107
Hypothalamic Insulin Resistance in Obesity: Effects on Glucose Homeostasis
Chen, W., Balland, É., & Cowley, M. A. (2017) · Neuroendocrinology · doi:10.1159/000455865 · Cited by 101
Intranasal insulin enhances brain functional connectivity mediating the relationship between adiposity and subjective feeling of hunger
Kullmann, S., Heni, M., Veit, R., Scheffler, K., Machann, J., Häring, H., Fritsche, A., & Preissl, H. T. (2017) · Scientific Reports · doi:10.1038/s41598-017-01907-w · Cited by 93
Self-citation
Brain Metabolism Alterations in Type 2 Diabetes: What Did We Learn From Diet-Induced Diabetes Models?
García-Serrano, A. M., & Duarte, J. M. N. (2020) · Frontiers in Neuroscience · doi:10.3389/fnins.2020.00229 · Cited by 95
Exercise restores brain insulin sensitivity in sedentary adults who are overweight and obese
Kullmann, S., Goj, T., Veit, R., Fritsche, L., Wagner, L., Schneeweiß, P., Hoene, M., Hoffmann, C., Machann, J., Niess, A. M., et al. (2022) · JCI Insight · doi:10.1172/jci.insight.161498 · Cited by 97
Self-citation
Important roles of linoleic acid and α-linolenic acid in regulating cognitive impairment and neuropsychiatric issues in metabolic-related dementia
Kim, O. Y., & Song, J. (2023) · Life Sciences · doi:10.1016/j.lfs.2023.122356 · Cited by 96
Melatonin alleviates cognition impairment by antagonizing brain insulin resistance in aged rats fed a high‐fat diet
Xu, J., Gao, H. Y., Zhang, L., Rong, S., Yang, W. Q., Ma, C., Chen, M., Huang, Q., Deng, Q., & Huang, F. (2019) · Journal of Pineal Research · doi:10.1111/jpi.12584 · Cited by 93
Thymol improves high-fat diet-induced cognitive deficits in mice via ameliorating brain insulin resistance and upregulating NRF2/HO-1 pathway
Fangfang, Li, H., Qin, T., Li, M., & Ma, S. (2016) · Metabolic Brain Disease · doi:10.1007/s11011-016-9921-z · Cited by 88
Benefits of Substituting Sitting with Standing and Walking in Free-Living Conditions for Cardiometabolic Risk Markers, Cognition and Mood in Overweight Adults
Duvivier, B. M. F. M., Schaper, N. C., Koster, A., van Kan, L., Peters, H. P. F., Adam, J. J., Giesbrecht, T., Moonen‐Kornips, E., Hulsbosch, M. M., Willems, P. J. B., et al. (2017) · Frontiers in Physiology · doi:10.3389/fphys.2017.00353 · Cited by 94
Reorganization of brain connectivity in obesity
Geha, P., Cecchi, G., Constable, R. T., Abdallah, C. G., & Small, D. M. (2016) · Human Brain Mapping · doi:10.1002/hbm.23462 · Cited by 85
Insulin sensitivity predicts cognitive decline in individuals with prediabetes
Willmann, C., Brockmann, K., Wagner, R. J., Kullmann, S., Preissl, H. T., Schnauder, G., Maetzler, W., Gasser, T., Berg, D., Eschweiler, G. W., et al. (2020) · BMJ Open Diabetes Research & Care · doi:10.1136/bmjdrc-2020-001741 · Cited by 95
Self-citation
Insulin Resistance is Associated with Increased Levels of Cerebrospinal Fluid Biomarkers of Alzheimer’s Disease and Reduced Memory Function in At-Risk Healthy Middle-Aged Adults
Hoscheidt, S. M., Starks, E. J., Oh, J. M., Zetterberg, H., Blennow, K., Krause, R. A., Gleason, C. E., Puglielli, L., Atwood, C., Carlsson, C. M., et al. (2016) · Journal of Alzheimer s Disease · doi:10.3233/jad-160110 · Cited by 84
Cerebral cortex: a target and source of insulin?
Csajbók, É., & Tamás, G. (2016) · Diabetologia · doi:10.1007/s00125-016-3996-2 · Cited by 85
Dose-Dependent Effects of Intranasal Insulin on Resting-State Brain Activity
Kullmann, S., Veit, R., Peter, A., Pohmann, R., Scheffler, K., Häring, H.-U., Fritsche, A., Preissl, H., & Heni, M. (2018) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2017-01976 · Cited by 78
Self-citation
Lymnaea stagnalis as model for translational neuroscience research: From pond to bench
Rivi, V., Benatti, C., Colliva, C., Radighieri, G., Brunello, N., Tascedda, F., & Blom, J. M. C. (2019) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2019.11.020 · Cited by 79
Insulin action in the brain: Roles in energy and glucose homeostasis
Dodd, G. T., & Tiganis, T. (2017) · Journal of Neuroendocrinology · doi:10.1111/jne.12513 · Cited by 77
High-Fat-Diet-Induced Deficits in Dopamine Terminal Function Are Reversed by Restoring Insulin Signaling
Fordahl, S. C., & Jones, S. R. (2016) · ACS Chemical Neuroscience · doi:10.1021/acschemneuro.6b00308 · Cited by 76
Roles for osteocalcin in brain signalling: implications in cognition- and motor-related disorders
Shan, C., Ghosh, A., Guo, X., Wang, S., Hou, Y., Li, S., & Liu, J. (2019) · Molecular Brain · doi:10.1186/s13041-019-0444-5 · Cited by 78
Long-term high-fat diet induces hippocampal microvascular insulin resistance and cognitive dysfunction
Fu, Z., Wu, J., Nesil, T., Li, M. D., Aylor, K. W., & Liu, Z. (2016) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00297.2016 · Cited by 74
Insulin and Its Key Role for Mitochondrial Function/Dysfunction and Quality Control: A Shared Link between Dysmetabolism and Neurodegeneration
Galizzi, G., & Carlo, M. D. (2022) · Biology · doi:10.3390/biology11060943 · Cited by 77
Characterisation of nasal devices for delivery of insulin to the brain and evaluation in humans using functional magnetic resonance imaging
Wingrove, J., Swedrowska, M., Scherließ, R., Parry, M., Ramjeeawon, M., Taylor, D., Gauthier, G., Brown, L., Amiel, S., Zelaya, F., et al. (2019) · Journal of Controlled Release · doi:10.1016/j.jconrel.2019.03.032 · Cited by 67
Deciphering Brain Insulin Receptor and Insulin‐Like Growth Factor 1 Receptor Signalling
Kleinridders, A. (2016) · Journal of Neuroendocrinology · doi:10.1111/jne.12433 · Cited by 67
Insulin‐degrading enzyme: an ally against metabolic and neurodegenerative diseases
Sousa, L., Guarda, M., Meneses, M. J., Macedo, M. P., & Miranda, H. V. (2021) · The Journal of Pathology · doi:10.1002/path.5777 · Cited by 67
Body–Brain Connections: The Effects of Obesity and Behavioral Interventions on Neurocognitive Aging
Stillman, C. M., Weinstein, A. M., Marsland, A. L., Gianaros, P. J., & Erickson, K. I. (2017) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2017.00115 · Cited by 69
Migraine, Brain Glucose Metabolism and the “Neuroenergetic” Hypothesis: A Scoping Review
Moro, L. D., Rota, E., Pirovano, E., & Rainero, I. (2022) · Journal of Pain · doi:10.1016/j.jpain.2022.02.006 · Cited by 66
Brain insulin, insulin‐like growth factor 1 and glucagon‐like peptide 1 signalling in Alzheimer’s disease
Ferreira, S. T. (2021) · Journal of Neuroendocrinology · doi:10.1111/jne.12959 · Cited by 59
Effects of Diabetes Mellitus-Related Dysglycemia on the Functions of Blood–Brain Barrier and the Risk of Dementia
Wątroba, M., Grabowska, A. D., & Szukiewicz, D. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms241210069 · Cited by 65
Mechanisms Underlying Brain Aging Under Normal and Pathological Conditions
Jin, M., & Cai, S. (2022) · Neuroscience Bulletin · doi:10.1007/s12264-022-00969-9 · Cited by 61
Hot Spots for the Use of Intranasal Insulin: Cerebral Ischemia, Brain Injury, Diabetes Mellitus, Endocrine Disorders and Postoperative Delirium
Shpakov, A. O., Zorina, I. I., & Derkach, K. V. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24043278 · Cited by 59
Design and development of chitosan-insulin-transfersomes (Transfersulin) as effective intranasal nanovesicles for the treatment of Alzheimer’s disease: In vitro, in vivo, and ex vivo evaluations
Nojoki, F., Ebrahimi-Hosseinzadeh, B., Hatamian-Zarmi, A., Khodagholi, F., & Khezri, K. (2022) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2022.113450 · Cited by 56
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
Novel phenotypes of prediabetes?
Häring, H. (2016) · Diabetologia · doi:10.1007/s00125-016-4015-3 · Cited by 54
Self-citation
Intranasal insulin therapy reverses hippocampal dendritic injury and cognitive impairment in a model of HIV-associated neurocognitive disorders in EcoHIV-infected mice
Kim, B.-H., Kelschenbach, J., Borjabad, A., Hadas, E., He, H., Potash, M. J., Nedelcovych, M. T., Rais, R., Haughey, N. J., McArthur, J. C., et al. (2019) · AIDS · doi:10.1097/qad.0000000000002150 · Cited by 53
Altered Odor-Induced Brain Activity as an Early Manifestation of Cognitive Decline in Patients With Type 2 Diabetes
Zhang, Z., Zhang, B., Wang, X., Zhang, X., Yang, Q. X., Zhao, Q., Lu, J., Bi, Y., & Zhu, D. (2018) · Diabetes · doi:10.2337/db17-1274 · Cited by 50
Brain insulin action on peripheral insulin sensitivity in women depends on menstrual cycle phase
Hummel, J., Benkendorff, C., Fritsche, L., Prystupa, K., Vosseler, A., Gancheva, S., Trenkamp, S., Birkenfeld, A. L., Preissl, H., Roden, M., et al. (2023) · Nature Metabolism · doi:10.1038/s42255-023-00869-w · Cited by 48
Self-citation
Functional subdivisions of the hypothalamus using areal parcellation and their signal changes related to glucose metabolism
Osada, T., Suzuki, R., Ogawa, A., Tanaka, M., Hori, M., Aoki, S., Tamura, Y., Watada, H., Kawamori, R., & Konishi, S. (2017) · NeuroImage · doi:10.1016/j.neuroimage.2017.08.056 · Cited by 48
Metabolomic and glycomic findings in posttraumatic stress disorder
Konjevod, M., Tudor, L., Štrac, D. Š., Erjavec, G. N., Barbas, C., Žarković, N., Perković, M. N., Uzun, S., Kozumplik, O., Lauc, G., et al. (2018) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2018.07.014 · Cited by 49
The role of mitochondrial reactive oxygen species in insulin resistance
Ayer, A., Fazakerley, D. J., James, D. E., & Stocker, R. (2021) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2021.11.007 · Cited by 50
Interaction between the obesity-risk gene FTO and the dopamine D2 receptor gene ANKK1/TaqIA on insulin sensitivity
Heni, M., Kullmann, S., Ahlqvist, E., Wagner, R. J., Machicao, F. E., Staiger, H., Häring, H.-U., Almgren, P., Groop, L., Small, D. M., et al. (2016) · Diabetologia · doi:10.1007/s00125-016-4095-0 · Cited by 47
Self-citation
Investigating obesity‐associated brain inflammation using quantitative water content mapping
Kullmann, S., Abbas, Z., Machann, J., Shah, N. J., Scheffler, K., Birkenfeld, A. L., Häring, H., Fritsche, A., Heni, M., & Preissl, H. T. (2020) · Journal of Neuroendocrinology · doi:10.1111/jne.12907 · Cited by 46
Self-citation
Leptin Signaling in the Arcuate Nucleus Reduces Insulin’s Capacity to Suppress Hepatic Glucose Production in Obese Mice
Balland, E., Chen, W., Dodd, G. T., Conductier, G., Coppari, R., Tiganis, T., & Cowley, M. A. (2019) · Cell Reports · doi:10.1016/j.celrep.2018.12.061 · Cited by 44
The Role of Thyroid Dysfunction in Alzheimer's Disease: A Systematic Review and Meta-Analysis
Salehipour, A., Dolatshahi, M., Haghshomar, M., & Amin, J. (2023) · The Journal of Prevention of Alzheimer s Disease · doi:10.14283/jpad.2023.20 · Cited by 43
Oral peptide therapeutics for diabetes treatment: State-of-the-art and future perspectives
Ding, B., Zhu, Z., Guo, C., Li, J., Gan, Y., & Yu, M. (2024) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2024.02.019 · Cited by 43
P21-activated kinase 2 (PAK2) regulates glucose uptake and insulin sensitivity in neuronal cells
Varshney, P., & Dey, C. S. (2016) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2016.03.035 · Cited by 42
GLP-1 and hunger modulate incentive motivation depending on insulin sensitivity in humans
Hanßen, R., Kretschmer, A. C., Rigoux, L., Albus, K., Thanarajah, S. E., Sitnikow, T., Melzer, C., Cornely, O. A., Brüning, J. C., & Tittgemeyer, M. (2021) · Molecular Metabolism · doi:10.1016/j.molmet.2021.101163 · Cited by 42
HMGB1 signaling pathway in diabetes-related dementia: Blood-brain barrier breakdown, brain insulin resistance, and Aβ accumulation
Jeong, J., Lee, D. H., & Song, J. (2022) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2022.112933 · Cited by 40
Type 2 diabetes risk gene Dusp8 regulates hypothalamic Jnk signaling and insulin sensitivity
Schriever, S. C., Kabra, D. G., Pfuhlmann, K., Baumann, P., Baumgart, E. V., Nagler, J., Seebacher, F., Harrison, L. P., Irmler, M., Kullmann, S., et al. (2020) · Journal of Clinical Investigation · doi:10.1172/jci136363 · Cited by 38
Self-citation
Effects of Intranasal Insulin Administration on Cerebral Blood Flow and Cognitive Performance in Adults: A Systematic Review of Randomized, Placebo-Controlled Intervention Studies
Nijssen, K. M. R., Mensink, R. P., & Joris, P. J. (2022) · Neuroendocrinology · doi:10.1159/000526717 · Cited by 43
Outcomes and clinical implications of intranasal insulin administration to the central nervous system
Santiago, J. C. P., & Hallschmid, M. (2019) · Experimental Neurology · doi:10.1016/j.expneurol.2019.03.007 · Cited by 37
Insulin Signaling as a Key Moderator in Myotonic Dystrophy Type 1
Nieuwenhuis, S., Okkersen, K., Widomska, J., Blom, P., Hoen, P. A. C. ’., van Engelen, B. G. M., & Glennon, J. C. (2019) · Frontiers in Neurology · doi:10.3389/fneur.2019.01229 · Cited by 38
Insulin Action in the Hypothalamus Increases Second-Phase Insulin Secretion in Humans
Heni, M., Wagner, R., Willmann, C., Jaghutriz, B. A., Vosseler, A., Kübler, C., Hund, V., Scheffler, K., Peter, A., Häring, H.-U., et al. (2020) · Neuroendocrinology · doi:10.1159/000504551 · Cited by 36
Self-citation
Acute changes in systemic glycemia gate access and action of GLP-1R agonist on brain structures controlling energy homeostasis
Bakker, W., Imbernón, M., Salinas, C. G., Chao, D. H. M., Hassouna, R., Morel, C., Martin, C., Leger, C., Denis, R., Castel, J., et al. (2022) · Cell Reports · doi:10.1016/j.celrep.2022.111698 · Cited by 37
Self-citation
Iron and Targeted Iron Therapy in Alzheimer’s Disease
Wang, J., Fu, J., Zhao, Y., Liu, Q., Yan, X., & Su, J. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms242216353 · Cited by 35
The Role of Insulin Resistance and Protein O-GlcNAcylation in Neurodegeneration
Ansari, S. A., & Emerald, B. S. (2019) · Frontiers in Neuroscience · doi:10.3389/fnins.2019.00473 · Cited by 36
Awake, long-term intranasal insulin treatment does not affect object memory, odor discrimination, or reversal learning in mice
Bell, G. A., & Fadool, D. A. (2017) · Physiology & Behavior · doi:10.1016/j.physbeh.2017.02.044 · Cited by 34
Objectively measured physical activity and cognitive function in urban‐dwelling older adults
Umegaki, H., Makino, T., Uemura, K., Shimada, H., Cheng, X. W., & Kuzuya, M. (2018) · Geriatrics and gerontology international/Geriatrics & gerontology international · doi:10.1111/ggi.13284 · Cited by 36
Insulin signalling in hypothalamic neurones
Belsham, D. D., & Dalvi, P. S. (2020) · Journal of Neuroendocrinology · doi:10.1111/jne.12919 · Cited by 35
Neuronal Food Reward Activity in Patients With Type 2 Diabetes With Improved Glycemic Control After Bariatric Surgery
Frank, S., Heinze, J. M., Fritsche, A., Linder, K., von Feilitzsch, M., Königsrainer, A., Häring, H., Veit, R., & Preissl, H. T. (2016) · Diabetes Care · doi:10.2337/dc16-0094 · Cited by 32
Self-citation
Pathways of Prevention: A Scoping Review of Dietary and Exercise Interventions for Neurocognition
Smith, P. J. (2019) · Brain Plasticity · doi:10.3233/bpl-190083 · Cited by 35
Sex-Specific Associations of Testosterone With Metabolic Traits
Lutz, S. Z., Wagner, R. J., Fritsche, L., Peter, A., Rettig, I., Willmann, C., Fehlert, E., Martus, P., Todenhöfer, T., Stefan, N., et al. (2019) · Frontiers in Endocrinology · doi:10.3389/fendo.2019.00090 · Cited by 31
Self-citation
Hypothalamic insulin responsiveness is associated with pancreatic insulin secretion in humans
Kullmann, S., Fritsche, A., Wagner, R. J., Schwab, S., Häring, H., Preissl, H. T., & Heni, M. (2017) · Physiology & Behavior · doi:10.1016/j.physbeh.2017.03.036 · Cited by 31
Self-citation
Neuroanatomical changes in white and grey matter after sleeve gastrectomy
Michaud, A., Dadar, M., Pelletier, M., Zeighami, Y., García‐García, I., Iceta, S., Yau, Y. H. C., Nadeau, M., Marceau, S., Biertho, L. D., et al. (2020) · NeuroImage · doi:10.1016/j.neuroimage.2020.116696 · Cited by 31
Association between thyroid function and Alzheimer's disease: A systematic review
Figueroa, P. B. S., Ferreira, A. F. F., Britto, L. R., Doussoulin, A. P., & Torrão, A. D. S. (2021) · Metabolic Brain Disease · doi:10.1007/s11011-021-00760-1 · Cited by 28
Persistent Leptin Signaling in the Arcuate Nucleus Impairs Hypothalamic Insulin Signaling and Glucose Homeostasis in Obese Mice
Balland, É., Chen, W., Tiganis, T., & Cowley, M. A. (2019) · Neuroendocrinology · doi:10.1159/000500201 · Cited by 31
Metabolic and Cognitive Outcomes of Subchronic Once-Daily Intranasal Insulin Administration in Healthy Men
Ritze, Y., Kern, W., Ebner, E.-M., Jahn, S., Benedict, C., & Hallschmid, M. (2018) · Frontiers in Endocrinology · doi:10.3389/fendo.2018.00663 · Cited by 28
Non-Invasive Techniques of Nose to Brain Delivery Using Nanoparticulate Carriers: Hopes and Hurdles
Butola, M., & Nainwal, N. (2024) · AAPS PharmSciTech · doi:10.1208/s12249-024-02946-z · Cited by 35

Authors: Heni, M., Kullmann, S., Preissl, H., Fritsche, A., & Häring, H.-U.
Affiliations: German Center for Diabetes Research (DE)
Corresponding author: Heni, Martin
ORCID: Heni, Martin
Kullmann, Stephanie
Preissl, Hubert
Fritsche, Andreas
Häring, Hans-Ulrich
Venue: Nature Reviews Endocrinology
Publisher: Springer Science and Business Media LLC
Published: 2015-10-13
Volume: 11
Issue: 12
Pages: 701-711
ISSN: 1759-5029 (ISSN-L)
1759-5037
DOI: 10.1038/nrendo.2015.173
OpenAlex: W2199402593
Cited by: 245
References: 158
Citations by year: 2026: 15 · 2025: 7 · 2024: 10 · 2023: 22 · 2022: 28 · 2021: 24 · 2020: 25 · 2019: 32 · 2018: 23 · 2017: 28 · 2016: 29 · 2015: 1
FWCI: 2.92
Type: journal article
Language: en
Open access: closed
Licence: www.springer.com/tdm (tdm)
Locations: Nature Reviews Endocrinology (publishedVersion)
PubMed (publishedVersion)
Site cant be reached (submittedVersion)
Funders: Bundesministerium für Bildung und Forschung
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 › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
Keywords: brain insulin resistance, obesity, type 2 diabetes, visceral fat, saturated fatty acids, blood-brain barrier, genetic polymorphism, food intake regulation, energy metabolism, whole-body glucose metabolism, lipid metabolism, cognitive function, eating behaviour
MeSH terms: Body Weight, Brain Chemistry, Cognition, Diabetes Mellitus, Type 2, Feeding Behavior, Humans, Insulin, Insulin Resistance

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

Impaired insulin action in the human brain: causes and metabolic consequences

Abstract

Overview

Integrity signals

Verification

Claims the paper makes

Claims other papers make about this one

Citations

Cites

Cited by

Related

Metadata

Record

About these checks