Selective Insulin Resistance in Homeostatic and Cognitive Control Brain Areas in Overweight and Obese Adults
Abstract
OBJECTIVE: Impaired brain insulin action has been linked to obesity, type 2 diabetes, and neurodegenerative diseases. To date, the central nervous effects of insulin in obese humans still remain ill defined, and no study thus far has evaluated the specific brain areas affected by insulin resistance. RESEARCH DESIGN AND METHODS: In 25 healthy lean and 23 overweight/obese participants, we performed magnetic resonance imaging to measure cerebral blood flow (CBF) before and 15 and 30 min after application of intranasal insulin or placebo. Additionally, participants explicitly rated pictures of high-caloric savory and sweet food 60 min after the spray for wanting and liking. RESULTS: In response to insulin compared with placebo, we found a significant CBF decrease in the hypothalamus in both lean and overweight/obese participants. The magnitude of this response correlated with visceral adipose tissue independent of other fat compartments. Furthermore, we observed a differential response in the lean compared with the overweight/obese group in the prefrontal cortex, resulting in an insulin-induced CBF reduction in lean participants only. This prefrontal cortex response significantly correlated with peripheral insulin sensitivity and eating behavior measures such as disinhibition and food craving. Behaviorally, we were able to observe a significant reduction for the wanting of sweet foods after insulin application in lean men only. CONCLUSIONS: Brain insulin action was selectively impaired in the prefrontal cortex in overweight and obese adults and in the hypothalamus in participants with high visceral adipose tissue, potentially promoting an altered homeostatic set point and reduced inhibitory control contributing to overeating behavior.
Integrity signals
Registry
Cites
Statistics
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 previous placebo-controlled assessments, the placebo nasal spray did not impact hypothalamic blood flow.
“However, in our previous placebo-controlled assessments6,8,39 (see Supplementary Material 2 for more details), the placebo nasal spray did not impact hypothalamic blood flow.”
From Brain insulin action on peripheral insulin sensitivity in women depends on menstrual cycle phase (2023) · cites this paper as [8]
The authors evaluated hypothalamic CBF response before and 30 min after placebo administration based on previous publications.
“we evaluated hypothalamic CBF response before and 30 min after placebo administration based on previous publications8,39.”
From Brain insulin action on peripheral insulin sensitivity in women depends on menstrual cycle phase (2023) · cites this paper as [8]
Insulin-induced response of hypothalamic cerebral blood flow is a readout for hypothalamic insulin action.
“On the basis of our previous findings3,8, we assessed the insulin-induced response of hypothalamic cerebral blood flow (CBF) as a readout for hypothalamic insulin action.”
From Brain insulin action on peripheral insulin sensitivity in women depends on menstrual cycle phase (2023) · cites this paper as [8]
CBF was extracted from the hypothalamus as the region of interest, based on recent findings.
“CBF was extracted from the hypothalamus as our region of interest, based on recent findings3,8.”
From Brain insulin action on peripheral insulin sensitivity in women depends on menstrual cycle phase (2023) · cites this paper as [8]
For the fMRI study, the sample size was chosen based on previous studies using fMRI in combination with intranasal insulin versus placebo showing moderate-to-high within-group (dz = 0.7) and high between-group differences (dz = 0.9) in hypothalamus insulin action.
“For the fMRI study, the sample size was chosen based on previous studies using fMRI in combination with intranasal insulin versus placebo showing moderate-to-high within-group (dz = 0.7) and high between-group differences (dz = 0.9) in hypothalamus insulin action8,48.”
From Brain insulin action on peripheral insulin sensitivity in women depends on menstrual cycle phase (2023) · cites this paper as [8]
No significant change in hypothalamic blood flow was observed in 110 healthy participants (P > 0.05).
“No significant change in hypothalamic blood flow was observed in 110 healthy participants (P > 0.05).”
From Brain insulin action on peripheral insulin sensitivity in women depends on menstrual cycle phase (2023) · cites this paper as [8]
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
Matsuda, M., & DeFronzo, R. A. (1999) · Diabetes Care · doi:10.2337/diacare.22.9.1462 · Cited by 5,621 · see citing works
Sniffing neuropeptides: A transnasal approach to the human brain
Born, J., Lange, T., Kern, W., McGregor, G. P., Bickel, U., & Fehm, H. L. (2002) · Nature Neuroscience · doi:10.1038/nn0602-849 · Cited by 1,356 · see citing works
Hypothalamic insulin signaling is required for inhibition of glucose production
Obici, S., Zhang, B. B., Karkanias, G., & Rossetti, L. (2002) · Nature Medicine · doi:10.1038/nm1202-798 · Cited by 904 · see citing works
The tempted brain eats: Pleasure and desire circuits in obesity and eating disorders
Berridge, K. C., Ho, C.-Y., Richard, J. M., & DiFeliceantonio, A. G. (2010) · Brain Research · doi:10.1016/j.brainres.2010.04.003 · Cited by 873 · see citing works
Metabolically healthy obesity: Epidemiology, mechanisms, and clinical implications
Stefan, N., Häring, H.-U., Hu, F. B., & Schulze, M. B. (2013) · The Lancet Diabetes & Endocrinology · doi:10.1016/s2213-8587(13)70062-7 · Cited by 857 · see citing works
Self-citationNeurobiology of food intake in health and disease
Morton, G. J., Meek, T. H., & Schwartz, M. W. (2014) · Nature Reviews Neuroscience · doi:10.1038/nrn3745 · Cited by 748 · see citing works
van der Laan, L. N., de Ridder, D. T. D., Viergever, M. A., & Smeets, P. A. M. (2010) · NeuroImage · doi:10.1016/j.neuroimage.2010.11.055 · Cited by 602 · see citing works
Cooper, Z., & Fairburn, C. G. (1987) · PsycTESTS Dataset · doi:10.1037/t03975-000 · Cited by 498 · see citing works
Empirical optimization of ASL data analysis using an ASL data processing toolbox: ASLtbx
Wang, Z., Aguirre, G. K., Rao, H., Wang, J., Fernández‐Seara, M. A., Childress, A. R., & Detre, J. A. (2007) · Magnetic Resonance Imaging · doi:10.1016/j.mri.2007.07.003 · Cited by 479 · see citing works
Intranasal Insulin Reduces Body Fat in Men but not in Women
Hallschmid, M., Benedict, C., Schultes, B., Fehm, H.-L., Born, J., & Kern, W. (2004) · Diabetes · doi:10.2337/diabetes.53.11.3024 · Cited by 281 · see citing works
Central insulin action regulates peripheral glucose and fat metabolism in mice
Koch, L., Wunderlich, F. T., Seibler, J., Könner, A. C., Hampel, B., Irlenbusch, S., Brabant, G. E., Kahn, C. R., Schwenk, F., & Brüning, J. C. (2008) · Journal of Clinical Investigation · doi:10.1172/jci31073 · Cited by 270 · see citing works
Standardized assessment of whole body adipose tissue topography by MRI
Machann, J., Thamer, C., Schnoedt, B., Haap, M., Haring, H., Claussen, C., Stumvoll, M., Fritsche, A., & Schick, F. (2005) · Journal of Magnetic Resonance Imaging · doi:10.1002/jmri.20292 · Cited by 266 · see citing works
Self-citationDelParigi, A., Chen, K., Salbe, A. D., Hill, J. O., Wing, R. R., Reiman, E. M., & Tataranni, P. A. (2007) · International Journal of Obesity · doi:10.1038/sj.ijo.0803431 · Cited by 255 · see citing works
Nijs, I., Franken, I., & Muris, P. (2007) · Appetite · doi:10.1016/j.appet.2006.11.001 · Cited by 235 · see citing works
Tschritter, O., Preissl, H., Hennige, A. M., Stumvoll, M., Porubska, K., Frost, R., Marx, H., Klösel, B., Lutzenberger, W., Birbaumer, N., et al. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0604404103 · Cited by 223 · see citing works
Self-citationBond, M. J., McDowell, A. J., & Wilkinson, J. Y. (2001) · International Journal of Obesity · doi:10.1038/sj.ijo.0801611 · Cited by 222 · see citing works
Neural Correlates of Stress- and Food Cue–Induced Food Craving in Obesity
Jastreboff, A. M., Sinha, R., Lacadie, C., Small, D. M., Sherwin, R. S., & Potenza, M. N. (2013) · Diabetes Care · doi:10.2337/dc12-1112 · Cited by 204 · see citing works
MRI atlas of the human hypothalamus
Baroncini, M., Jissendi, P., Balland, É., Besson, P., Pruvo, J., Francke, J.-P., Dewailly, D., Blond, S., & Prévot, V. (2011) · NeuroImage · doi:10.1016/j.neuroimage.2011.07.013 · Cited by 190 · see citing works
Hallschmid, M., Higgs, S., Thienel, M., Ott, V., & Lehnert, H. (2012) · Diabetes · doi:10.2337/db11-1390 · Cited by 181 · see citing works
Heni, M., Wagner, R., Kullmann, S., Veit, R., Mat Husin, H., Linder, K., Benkendorff, C., Peter, A., Stefan, N., Häring, H.-U., et al. (2014) · Diabetes · doi:10.2337/db14-0477 · Cited by 167 · see citing works
Self-citationNeural Responses to Visual Food Cues: Insights from Functional Magnetic Resonance Imaging
García‐García, I., Narberhaus, A., Marqués‐Iturria, I., Garolera, M., Rădoi, A., Segura, B., Pueyo, R., Ariza, M., & Jurado, M. Á. (2013) · European Eating Disorders Review · doi:10.1002/erv.2216 · Cited by 166 · see citing works
McCaffery, J. M., Haley, A. P., Sweet, L. H., Phelan, S., Raynor, H. A., Del Parigi, A., Cohen, R., & Wing, R. R. (2009) · The American Journal of Clinical Nutrition · doi:10.3945/ajcn.2009.27924 · Cited by 161 · see citing works
Insulin Modulates Food-Related Activity in the Central Nervous System
Guthoff, M., Grichisch, Y., Canova, C., Tschritter, O., Veit, R., Hallschmid, M., Häring, H., Preissl, H. T., Hennige, A. M., & Fritsche, A. (2009) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2009-1677 · Cited by 157 · see citing works
Self-citationOtt, V., Benedict, C., Schultes, B., Born, J., & Hallschmid, M. (2012) · Diabetes, Obesity and Metabolism · doi:10.1111/j.1463-1326.2011.01490.x · Cited by 139 · see citing works
(Still) longing for food: Insulin reactivity modulates response to food pictures
Kroemer, N. B., Krebs, L., Kobiella, A., Grimm, O., Vollstädt‐Klein, S., Wolfensteller, U., Kling, R., Bidlingmaier, M., Zimmermann, U. S., & Smolka, M. N. (2012) · Human Brain Mapping · doi:10.1002/hbm.22071 · Cited by 111 · see citing works
Kullmann, S., Frank, S., Heni, M., Ketterer, C., Veit, R., Häring, H.-U., Fritsche, A., & Preissl, H. (2013) · Neuroendocrinology · doi:10.1159/000341406 · Cited by 110 · see citing works
Self-citationKullmann, S., Pape, A.-A., Heni, M., Ketterer, C., Schick, F., Häring, H., Fritsche, A., Preissl, H. T., & Veit, R. (2012) · Cerebral Cortex · doi:10.1093/cercor/bhs124 · Cited by 110 · see citing works
Self-citationHeni, M., Kullmann, S., Ketterer, C., Guthoff, M., Linder, K., Wagner, R. J., Stingl, K. T., Veit, R., Staiger, H., Häring, H., et al. (2012) · Diabetologia · doi:10.1007/s00125-012-2528-y · Cited by 109 · see citing works
Self-citationPotentials and Challenges for Arterial Spin Labeling in Pharmacological Magnetic Resonance Imaging
Wang, D. J. J., Chen, Y., Fernández‐Seara, M. A., & Detre, J. A. (2011) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.110.172577 · Cited by 105 · see citing works
Goldman, R. L., Canterberry, M., Borckardt, J. J., Madan, A., Byrne, T. K., George, M. S., O'Neil, P. M., & Hanlon, C. A. (2013) · Obesity · doi:10.1002/oby.20575 · Cited by 96 · see citing works
Regional reproducibility of pulsed arterial spin labeling perfusion imaging at 3T
Wang, Y., Saykin, A. J., Pfeuffer, J., Lin, C., Mosier, K. M., Shen, L., Kim, S., & Hutchins, G. D. (2010) · NeuroImage · doi:10.1016/j.neuroimage.2010.08.043 · Cited by 91 · see citing works
Comparison of pulsed arterial spin labeling encoding schemes and absolute perfusion quantification
Çavuşoğlu, M., Pfeuffer, J., Uǧurbil, K., & Uludaǧ, K. (2009) · Magnetic Resonance Imaging · doi:10.1016/j.mri.2009.04.002 · Cited by 85 · see citing works
Heni, M., Kullmann, S., Ketterer, C., Guthoff, M., Bayer, M., Staiger, H., Machicao, F. E., Häring, H., Preissl, H. T., Veit, R., et al. (2013) · Human Brain Mapping · doi:10.1002/hbm.22223 · Cited by 77 · see citing works
Self-citationHigh cerebral insulin sensitivity is associated with loss of body fat during lifestyle intervention
Tschritter, O., Preissl, H. T., Hennige, A. M., Sartorius, T., Štingl, K., Heni, M., Ketterer, C., Stefan, N., Machann, J., Schleicher, E., et al. (2011) · Diabetologia · doi:10.1007/s00125-011-2309-z · Cited by 63 · see citing works
Self-citationIntranasal Insulin Suppresses Systemic but Not Subcutaneous Lipolysis in Healthy Humans
Iwen, K. A., Scherer, T., Heni, M., Sayk, F., Wellnitz, T., Machleidt, F., Preissl, H., Häring, H.-U., Fritsche, A., Lehnert, H., et al. (2014) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2013-3169 · Cited by 59 · see citing works
Self-citationCerebrocortical 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 53 · see citing works
Self-citationFat intake modulates cerebral blood flow in homeostatic and gustatory brain areas in humans
Frank, S., Linder, K., Kullmann, S., Heni, M., Ketterer, C., Çavuşoğlu, M., Krzeminski, A., Fritsche, A., Häring, H., Preissl, H. T., et al. (2012) · American Journal of Clinical Nutrition · doi:10.3945/ajcn.111.031492 · Cited by 45 · see citing works
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
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 632 · see citing works
Self-citationUpadhyay, J., Farr, O. M., Perakakis, N., Ghaly, W., & Mantzoros, C. S. (2017) · Medical Clinics of North America · doi:10.1016/j.mcna.2017.08.004 · Cited by 403 · see citing works
The determinants of food choice
Leng, G., Adan, R. A. H., Belot, M., Brunstrom, J. M., de Graaf, K., Dickson, S. L., Hare, T. A., Maier, S. U., Menzies, J., Preissl, H., et al. (2016) · Proceedings of The Nutrition Society · doi:10.1017/s002966511600286x · Cited by 435 · see citing works
Self-citationThe determinants of food choice
Leng, G., Adan, R. A. H., Belot, M. V. K., Brunstrom, J. M., de Graaf, K. C., Dickson, S. L., Hare, T. A., Maier, S. U., Menzies, J. R. W., Preissl, H. T., et al. (2017) · Zurich Open Repository and Archive (University of Zurich) · doi:10.5167/uzh-146390 · Cited by 255 · see citing works
Self-citationImpaired insulin action in the human brain: causes and metabolic consequences
Heni, M., Kullmann, S., Preissl, H., Fritsche, A., & Häring, H.-U. (2015) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2015.173 · Cited by 245 · see citing works
Self-citationCentral nervous pathways of insulin action in the control of metabolism and food intake
Kullmann, S., Kleinridders, A., Small, D. M., Fritsche, A., Häring, H.-U., Preissl, H., & Heni, M. (2020) · The Lancet Diabetes & Endocrinology · doi:10.1016/s2213-8587(20)30113-3 · Cited by 233 · see citing works
Self-citationBrain insulin signalling in metabolic homeostasis and disease
Scherer, T., Sakamoto, K., & Buettner, C. (2021) · Nature Reviews Endocrinology · doi:10.1038/s41574-021-00498-x · Cited by 205 · see citing works
Central nervous system regulation of eating: Insights from human brain imaging
Farr, O. M., Li, C. R., & Mantzoros, C. S. (2016) · Metabolism · doi:10.1016/j.metabol.2016.02.002 · Cited by 191 · see citing works
Kleinloog, J., Mensink, R., Ivanov, D., Adam, J., Uludağ, K., & Joris, P. (2019) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2019.00333 · Cited by 153 · see citing works
Insulin in the nervous system and the mind: Functions in metabolism, memory, and mood
Lee, S.-H., Zabolotny, J. M., Huang, H., Lee, H., & Kim, Y.-B. (2016) · Molecular Metabolism · doi:10.1016/j.molmet.2016.06.011 · Cited by 176 · see citing works
Mansur, R. B., Ahmed, J., Cha, D. S., Woldeyohannes, H. O., Subramaniapillai, M., Lovshin, J. A., Lee, J. G., Lee, J.-H., Brietzke, E. M., Reininghaus, E. Z., et al. (2016) · Journal of Affective Disorders · doi:10.1016/j.jad.2016.09.056 · Cited by 163 · see citing works
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 135 · see citing works
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 · see citing works
Self-citationKelly, T., Unwin, D., & Finucane, F. M. (2020) · International Journal of Environmental Research and Public Health · doi:10.3390/ijerph17072557 · Cited by 133 · see citing works
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 · see citing works
Self-citationCentral 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 · see citing works
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 · see citing works
Self-citationKullmann, S., Hummel, J., Wagner, R. J., Dannecker, C., Vosseler, A., Fritsche, L., Veit, R., Kantartzis, K., Machann, J., Birkenfeld, A. L., et al. (2021) · Diabetes Care · doi:10.2337/dc21-1136 · Cited by 112 · see citing works
Self-citationMolecular Mechanisms of Hypothalamic Insulin Resistance
Ono, H. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20061317 · Cited by 107 · see citing works
Brain energy metabolism: A roadmap for future research
Rae, C. D., Baur, J. A., Borges, K., Dienel, G. A., Díaz‐García, C. M., Douglass, S. R., Drew, K. L., Duarte, J. M. N., Durán, J., Kann, O., et al. (2024) · Journal of Neurochemistry · doi:10.1111/jnc.16032 · Cited by 109 · see citing works
Hypothalamic Control of Systemic Glucose Homeostasis: The Pancreas Connection
Pozo, M., & Claret, M. (2018) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2018.05.001 · Cited by 97 · see citing works
Non-Invasive Strategies for Nose-to-Brain Drug Delivery.
Ja, T., Quispe, R. C., Khan, F., & Новак (2020) · PubMed · Cited by 95 · see citing works
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 92 · see citing works
Self-citationExercise 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 93 · see citing works
Self-citationShpakov, A. O., Derkach, K. V., & Berstein, L. M. (2015) · Future Science OA · doi:10.4155/fso.15.23 · Cited by 92 · see citing works
Circadian desynchrony and glucose metabolism
Speksnijder, E. M., Bisschop, P. H. L. T., Siegelaar, S. E., Stenvers, D. J., & Kalsbeek, A. (2024) · Journal of Pineal Research · doi:10.1111/jpi.12956 · Cited by 98 · see citing works
Gruber, J., Hanßen, R., Qubad, M., Bouzouina, A., Schack, V., Sochor, H., Schiweck, C., Aichholzer, M., Matura, S., Slattery, D. A., et al. (2023) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2023.105179 · Cited by 91 · see citing works
Impaired peripheral glucose homeostasis and Alzheimer's disease
Wijesekara, N., Gonçalves, R. A., Felice, F. G. D., & Fraser, P. E. (2017) · Neuropharmacology · doi:10.1016/j.neuropharm.2017.11.027 · Cited by 80 · see citing works
Woo, Y., Seo, H.-J., McIntyre, R., & Bahk, W.-M. (2016) · International Journal of Molecular Sciences · doi:10.3390/ijms17010080 · Cited by 79 · see citing works
Bae, C. S., & Song, J. (2017) · International Journal of Molecular Sciences · doi:10.3390/ijms18112493 · Cited by 79 · see citing works
Imaging of intranasal drug delivery to the brain.
Veronesi, M. C., Alhamami, M., Miedema, S. B., Yun, Y., Ruiz-Cardozo, M. A., & Vannier, M. W. (2020) · PubMed Central · Cited by 78 · see citing works
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 · see citing works
Self-citationInsulin 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 75 · see citing works
Insulin Resistance in Peripheral Tissues and the Brain: A Tale of Two Sites
Rhea, E. M., Banks, W. A., & Raber, J. (2022) · Biomedicines · doi:10.3390/biomedicines10071582 · Cited by 76 · see citing works
Borrajo, M. L., & Alonso, M. J. (2021) · Drug Delivery and Translational Research · doi:10.1007/s13346-021-01086-2 · Cited by 70 · see citing works
State of the science on brain insulin resistance and cognitive decline due to Alzheimer's disease
Rhea, E. M., Leclerc, M., Yassine, H. N., Capuano, A. W., Tong, H., Petyuk, V. A., Macauley, S. L., Fioramonti, X., Carmichael, O., Calon, F., et al. (2023) · Aging and disease · doi:10.14336/ad.2023.0814 · Cited by 70 · see citing works
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 · see citing works
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 65 · see citing works
Sleep Deprivation Selectively Upregulates an Amygdala–Hypothalamic Circuit Involved in Food Reward
Rihm, J. S., Menz, M. M., Schultz, H., Bruder, L. R., Schilbach, L., Schmid, S. M., & Peters, J. (2018) · Journal of Neuroscience · doi:10.1523/jneurosci.0250-18.2018 · Cited by 64 · see citing works
The insulin resistant brain: impact on whole-body metabolism and body fat distribution
Heni, M. (2024) · Diabetologia · doi:10.1007/s00125-024-06104-9 · Cited by 73 · see citing works
Self-citationLuo, Y., Wang, Q., & Zhang, Y. (2015) · Journal of Ethnopharmacology · doi:10.1016/j.jep.2015.12.011 · Cited by 64 · see citing works
The Complex Roles of Mechanistic Target of Rapamycin in Adipocytes and Beyond
Lee, P. L., Jung, S. M., & Guertin, D. A. (2017) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2017.01.004 · Cited by 64 · see citing works
Recent advances in understanding body weight homeostasis in humans
Müller, M. J., Geisler, C., Heymsfield, S. B., & Bosy‐Westphal, A. (2018) · F1000Research · doi:10.12688/f1000research.14151.1 · Cited by 61 · see citing works
The regulation of food intake by insulin in the central nervous system
Mitchell, C. S., & Begg, D. P. (2021) · Journal of Neuroendocrinology · doi:10.1111/jne.12952 · Cited by 60 · see citing works
Shpakov, A. O., Zorina, I. I., & Derkach, K. V. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24043278 · Cited by 57 · see citing works
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 · see citing works
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 · see citing works
Central Insulin Modulates Dopamine Signaling in the Human Striatum
Kullmann, S., Blum, D., Jaghutriz, B. A., Gassenmaier, C., Bender, B., Häring, H., Reischl, G., Preissl, H. T., la Fougère, C. J., Fritsche, A., et al. (2021) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/clinem/dgab410 · Cited by 54 · see citing works
Self-citationNovel phenotypes of prediabetes?
Häring, H. (2016) · Diabetologia · doi:10.1007/s00125-016-4015-3 · Cited by 53 · see citing works
Self-citationVanWagner, L. B., Terry, J. G., Chow, L. S., Alman, A. C., Kang, H., Ingram, K. H., Shay, C. M., Lewis, C. E., Bryan, R. N., Launer, L. J., et al. (2017) · Obesity · doi:10.1002/oby.21767 · Cited by 50 · see citing works
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 · see citing works
Self-citationSteward, T., Miranda‐Olivos, R., Soriano‐Mas, C., & Fernández‐Aranda, F. (2019) · Reviews in Endocrine and Metabolic Disorders · doi:10.1007/s11154-019-09515-x · Cited by 46 · see citing works
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 · see citing works
Self-citationThe Upper Nasal Space: Option for Systemic Drug Delivery, Mucosal Vaccines and “Nose-to-Brain”
Shrewsbury, S. B. (2023) · Pharmaceutics · doi:10.3390/pharmaceutics15061720 · Cited by 44 · see citing works
Olver, T. D., Grunewald, Z. I., Jurrissen, T. J., MacPherson, R. E. K., LeBlanc, P. J., Schnurbusch, T., Czajkowski, A. M., Laughlin, M. H., Rector, R. S., Bender, S. B., et al. (2017) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00213.2017 · Cited by 42 · see citing works
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 · see citing works
Self-citationNijssen, K. M. R., Mensink, R. P., & Joris, P. J. (2022) · Neuroendocrinology · doi:10.1159/000526717 · Cited by 39 · see citing works
Drummen, M., Dorenbos, E., Vreugdenhil, A. C. E., Raben, A., Westerterp‐Plantenga, M. S., & Adam, T. C. (2018) · American Journal of Clinical Nutrition · doi:10.1093/ajcn/nqy252 · Cited by 37 · see citing works
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 · see citing works
Self-citationIntranasal Neuropeptide Administration To Target the Human Brain in Health and Disease
Spetter, M. S., & Hallschmid, M. (2015) · Molecular Pharmaceutics · doi:10.1021/acs.molpharmaceut.5b00047 · Cited by 35 · see citing works
Schneider, E. M., Spetter, M. S., Martin, E., Sapey, E., Yip, K. P., Manolopoulos, K. N., Tahrani, A. A., Thomas, J. M., Lee, M. D., Hallschmid, M., et al. (2022) · International Journal of Obesity · doi:10.1038/s41366-022-01115-1 · Cited by 36 · see citing works
Ahmad, R. M. A. H., Ababneh, N. A., & Al-Domi, H. A. (2022) · Diabetes & Metabolic Syndrome Clinical Research & Reviews · doi:10.1016/j.dsx.2022.102468 · Cited by 34 · see citing works
Anderson, K. L., Frazier, H. N., Maimaiti, S., Bakshi, V., Majeed, Z. R., Brewer, L. D., Porter, N. M., Lin, A., & Thibault, O. (2016) · The Journals of Gerontology Series A · doi:10.1093/gerona/glw065 · Cited by 34 · see citing works
Chruvattil, R., Banerjee, S., Nath, S., Machhi, J., Kharkwal, G. B., Yadav, M. R., & Gupta, S. S. (2016) · Molecular Neurobiology · doi:10.1007/s12035-016-0251-2 · Cited by 32 · see citing works
Wagner, L., Veit, R., Fritsche, L., Häring, H., Fritsche, A., Birkenfeld, A. L., Heni, M., Preissl, H. T., & Kullmann, S. (2022) · International Journal of Obesity · doi:10.1038/s41366-022-01167-3 · Cited by 32 · see citing works
Self-citationHypothalamic 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 · see citing works
Self-citationHuang, X., Wang, Y., & Xiang, Y. (2022) · EBioMedicine · doi:10.1016/j.ebiom.2022.104263 · Cited by 31 · see citing works
A short-term, high-caloric diet has prolonged effects on brain insulin action in men
Kullmann, S., Wagner, L., Hauffe, R., Kühnel, A., Sandforth, L., Veit, R., Dannecker, C., Machann, J., Fritsche, A., Stefan, N., et al. (2025) · Nature Metabolism · doi:10.1038/s42255-025-01226-9 · Cited by 32 · see citing works
Self-citationNovel calcium-related targets of insulin in hippocampal neurons
Maimaiti, S., Frazier, H. N., Anderson, K. L., Ghoweri, A. O., Brewer, L. D., Porter, N. M., & Thibault, O. (2017) · Neuroscience · doi:10.1016/j.neuroscience.2017.09.019 · Cited by 29 · see citing works
Legend of Weight Loss: A Crosstalk Between the Bariatric Surgery and the Brain
Lin, Z., & Qu, S. (2020) · Obesity Surgery · doi:10.1007/s11695-020-04474-8 · Cited by 28 · see citing works
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 · see citing works
Wingrove, J. O., O’Daly, O., Forbes, B., Swedrowska, M., Amiel, S. A., & Zelaya, F. O. (2020) · Diabetes Obesity and Metabolism · doi:10.1111/dom.14213 · Cited by 28 · see citing works
Intranasal Insulin: a Treatment Strategy for Addiction
Kashyap, B., Hanson, L. R., & Frey, W. H. (2020) · Neurotherapeutics · doi:10.1007/s13311-019-00822-4 · Cited by 27 · see citing works
Yagin, N. L., Aliasgari, F., Alizadeh, M., Aliasgharzadeh, S., & Mahdavi, R. (2020) · Nutrition Research · doi:10.1016/j.nutres.2020.09.001 · Cited by 27 · see citing works
Heni, M., Kullmann, S., Gallwitz, B., Häring, H., Preissl, H. T., & Fritsche, A. (2015) · Molecular Metabolism · doi:10.1016/j.molmet.2015.09.007 · Cited by 28 · see citing works
Self-citationSmall, D. M. (2017) · Frontiers in Neuroscience · doi:10.3389/fnins.2017.00134 · Cited by 27 · see citing works
Chakravartti, S. P., Jann, K., Veit, R., Liu, H., Yunker, A. G., ANGELO, B. C., Monterosso, J. R., Xiang, A. H., Kullmann, S., & Page, K. A. (2025) · Nature Metabolism · doi:10.1038/s42255-025-01227-8 · Cited by 26 · see citing works
Self-citationHippocampal insulin resistance and altered food decision-making as players on obesity risk
Mucellini, A. B., da Fonseca, N. K. D. O., Manfro, G. G., & Silveira, P. P. (2017) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2017.03.011 · Cited by 26 · see citing works
Drummen, M., Dorenbos, E., Vreugdenhil, A. C. E., Stratton, G., Raben, A., Westerterp‐Plantenga, M. S., & Adam, T. C. (2018) · Nutrients · doi:10.3390/nu10111771 · Cited by 26 · see citing works
Aliasghari, F., Yagin, N. L., & Mahdavi, R. (2018) · Physiology & Behavior · doi:10.1016/j.physbeh.2018.11.013 · Cited by 25 · see citing works
Expanding the understanding of insulin resistance in brain and periphery
Chen, W., Kullmann, S., & Rhea, E. M. (2025) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2025.04.010 · Cited by 23 · see citing works
Self-citationMolecular imaging of diabetes and diabetic complications: Beyond pancreatic β-cell targeting
Yang, J., Zhang, L. J., Wang, F., Hong, T., & Liu, Z. (2018) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2018.11.007 · Cited by 24 · see citing works
Brain insulin responsiveness is linked to age and peripheral insulin sensitivity
Wagner, L., Veit, R., Kübler, C., Fritsche, A., Häring, H., Birkenfeld, A. L., Heni, M., Preissl, H., & Kullmann, S. (2023) · Diabetes, Obesity and Metabolism · doi:10.1111/dom.15094 · Cited by 22 · see citing works
Self-citationChildhood Metabolic Biomarkers Are Associated with Performance on Cognitive Tasks in Young Children
Shapiro, A. L. B., Wilkening, G. N., Aalborg, J., Ringham, B. M., Glueck, D. H., Tregellas, J. R., & Dabelea, D. (2019) · The Journal of Pediatrics · doi:10.1016/j.jpeds.2019.03.043 · Cited by 22 · see citing works
Camps, G., Veit, R., Mars, M., de Graaf, C., & Smeets, P. A. M. (2018) · Appetite · doi:10.1016/j.appet.2018.04.023 · Cited by 19 · see citing works
Self-citationAn insulin resistance associated neural correlate of impulsivity in type 2 diabetes mellitus
Eckstrand, K., Mummareddy, N., Kang, H., Cowan, R. L., Zhou, M., Zald, D. H., Silver, H. J., Niswender, K. D., & Avison, M. J. (2017) · PLoS ONE · doi:10.1371/journal.pone.0189113 · Cited by 18 · see citing works
The effect of hunger state on hypothalamic functional connectivity in response to food cues
Kullmann, S., Veit, R., Crabtree, D. R., Buosi, W., Androutsos, O., Johnstone, A. M., Μanios, Y., Preissl, H. T., & Smeets, P. A. M. (2022) · Human Brain Mapping · doi:10.1002/hbm.26059 · Cited by 18 · see citing works
Self-citationNijssen, K. M. R., Mensink, R. P., Plat, J., Ivanov, D., Preissl, H. T., & Joris, P. J. (2023) · American Journal of Clinical Nutrition · doi:10.1016/j.ajcnut.2023.12.010 · Cited by 18 · see citing works
Self-citationFrank, S., von Schnurbein, J., Veit, R., Heni, M., Machann, J., Heinze, J. M., Kullmann, S., Manzoor, J., Mahmood, S., Häring, H., et al. (2018) · Diabetes Care · doi:10.2337/dc17-1867 · Cited by 17 · see citing works
Self-citationBlasi, C. (2016) · Obesity Surgery · doi:10.1007/s11695-016-2419-2 · Cited by 16 · see citing works
An interoceptive model of energy allostasis linking metabolic and mental health
Mehrhof, S. Z., Fleming, H. A., & Nord, C. L. (2025) · Science Advances · doi:10.1126/sciadv.ady4356 · Cited by 16 · see citing works
Food reinforcement architecture: A framework for impulsive and compulsive overeating and food abuse
Burger, K. S. (2023) · Obesity · doi:10.1002/oby.23792 · Cited by 15 · see citing works
Cognitive profile in burning mouth syndrome versus mild cognitive impairment: A comparative study
Femminella, G. D., Canfora, F., Musella, G., Tella, G. S. D., Ugga, L., Pecoraro, G., Leuci, S., Coppola, N., Lucia, N. D., Maldonato, N. M., et al. (2024) · Oral Diseases · doi:10.1111/odi.15087 · Cited by 15 · see citing works
Plasma copeptin and metabolic dysfunction in individuals with bipolar disorder
Mansur, R. B., Rizzo, L. B., Santos, C. M., Asevedo, E. D. M., da Cunha, G. R., Noto, M. N., Pedrini, M., Zeni‐Graiff, M., Cordeiro, Q., McIntyre, R. S., et al. (2017) · Psychiatry and Clinical Neurosciences · doi:10.1111/pcn.12535 · Cited by 15 · see citing works
Ectopic fat accumulation in human astrocytes impairs insulin action
Heni, M., Eckstein, S. S., Schittenhelm, J., Böhm, A., Hogrefe, N., Irmler, M., Beckers, J., de Angelis, M. H., Häring, H., Fritsche, A., et al. (2020) · Royal Society Open Science · doi:10.1098/rsos.200701 · Cited by 11 · see citing works
Self-citationGalmiche, M. C., Lucas, N., Déchelotte, P., Deroissart, C., Solliec, M.-A. L., Rondeaux, J., Azhar, S., Grigioni, S., Colange, G., Delay, J., et al. (2020) · Nutrients · doi:10.3390/nu12020522 · Cited by 13 · see citing works
Inter-Organ Crosstalk in Neurodegenerative Disease
Carata, E., Destino, M., Tenuzzo, B. A., & Panzarini, E. (2025) · Life · doi:10.3390/life15101499 · Cited by 13 · see citing works
Kleinloog, J., Mensink, R., Smeets, E., Ivanov, D., & Joris, P. (2022) · NeuroImage: Clinical · doi:10.1016/j.nicl.2022.103115 · Cited by 9 · see citing works
Obesity May Connect Insulin Resistance to Decreased Neuronal Viability in Human Diabetic Brain
Lee, S. L., Joo, Y., Kim, R. Y., Hwang, J., Lim, S. M., Yoon, S. J., & Kim, J. (2020) · Obesity · doi:10.1002/oby.22869 · Cited by 11 · see citing works
Malkki-Keinänen, K., Lankinen, M. A., Karhunen, L. J., & Schwab, U. (2022) · Nutrition and Health · doi:10.1177/02601060221112178 · Cited by 10 · see citing works
- Authors
- Kullmann, S., Heni, M., Veit, R., Scheffler, K., Machann, J., Häring, H.-U., Fritsche, A., & Preissl, H.
- Affiliations
- German Center for Diabetes Research (DE)
- Max Planck Institute for Biological Cybernetics (DE)
- Corresponding author
- Kullmann, Stephanie
- ORCID
- Venue
- Diabetes Care
- Publisher
- American Diabetes Association
- Published
- 2015-03-20
- Volume
- 38
- Issue
- 6
- Pages
- 1044-1050
- ISSN
- 0149-5992 (ISSN-L)
- 1935-5548
- OpenAlex
- W2053859901
- Cited by
- 175
- References
- 38
- Citations by year
- 2026: 11 · 2025: 18 · 2024: 12 · 2023: 17 · 2022: 16 · 2021: 11 · 2020: 18 · 2019: 14 · 2018: 16 · 2017: 21 · 2016: 16 · 2015: 5
- FWCI
- 10.71
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Diabetes Care (publishedVersion)
- PubMed (publishedVersion)
- Max Planck Digital Library (submittedVersion)
- Site cant be reached (submittedVersion)
- MPG.PuRe (Max Planck Society) (submittedVersion)
- Funders
- German Federal Ministry of Education and Research (01GIL22F)
- Helmholtz Alliance ICEMED
- European Union Seventh Framework Programme (FP7/2007-2013)
- German Diabetes Foundation (DDS 309/01/12)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Social Sciences › Psychology › Clinical Psychology › Eating Disorders and Behaviors
- Keywords
- brain insulin resistance, intranasal insulin, cerebral blood flow, hypothalamus, prefrontal cortex, visceral adipose tissue, obesity, overweight, food cravings, desire to eat, disinhibition, dietary habits, homeostatic set point, inhibitory control, cognitive control
- MeSH terms
- Administration, Intranasal, Adult, Brain, Brain Mapping, Cerebrovascular Circulation, Cognition, Diabetes Mellitus, Type 2, Feeding Behavior, Female, Homeostasis, Humans, Hunger, Hypoglycemic Agents, Hypothalamus, Inhibition, Psychological, Insulin, Insulin Resistance, Magnetic Resonance Imaging, Male, Obesity, Body Mass Index, Prefrontal Cortex, Intra-Abdominal Fat, Overweight, Craving
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
