The DOI matches its Crossref record; 33 of the 33 references it cites were found in a registry or an index.
Intranasal Insulin Reduces Body Fat in Men but not in Women
Open accessAbstract
Insulin acts in the central nervous system to reduce food intake and body weight and is considered a major adiposity signal. After intranasal administration, insulin enters the cerebrospinal fluid compartment and alters brain functions in the absence of substantial absorption into the blood stream. Here we report the effects of 8 weeks of intranasal administration of insulin (4 × 40 IU/day) or placebo to two groups of healthy human subjects (12 men and 8 women in each group). The insulin-treated men lost 1.28 kg body wt and 1.38 kg of body fat, and their waist circumference decreased by 1.63 cm. Plasma leptin levels dropped by an average of 27%. In contrast, the insulin-treated women did not lose body fat and gained 1.04 kg body wt due to a rise in extracellular water. Our results provide a strong, first confirmation in humans that insulin acts as a negative feedback signal in the regulation of adiposity and point to a differential sensitivity to the catabolic effects of insulin based on sex.
Overview
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
Verification
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?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Indeed, intranasal insulin—which reaches the brain directly along olfactory perivascular channels—reduces body fat in men but not in women [33].”
From Sex differences in metabolic homeostasis, diabetes, and obesity (2015) · cites this paper as [33]
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“Of note, experimental studies suggest considerable sex differences in brain insulin sensitivity.”
From Brain insulin action on peripheral insulin sensitivity in women depends on menstrual cycle phase (2023) · cites this paper as [26]
The cited source says what the claim attributes to it.
In the citing paper
“Nevertheless, daily nasal insulin administration over 8 weeks reduced body weight and body fat content only in men, whereas women showed no reduction in body adiposity26.”
From Brain insulin action on peripheral insulin sensitivity in women depends on menstrual cycle phase (2023) · cites this paper as [26]
In the citing paper
“suggesting that delivery schedules synced to food intake 39,42,44,47 might be necessary for the catabolic impact of IN insulin to emerge.”
From Intranasal insulin (2021) · cites this paper as [42]
In the citing paper
“In healthy, normal-weight humans, IN insulin administration for 8 weeks (4 × 40 IU day -1 ) reduced body weight and body fat content in men, but not women.”
From Intranasal insulin (2021) · cites this paper as [42]
In the citing paper
“The loss of body fat in the men was associated with a 27% reduction in the circulating concentrations of leptin.”
From Intranasal insulin (2021) · cites this paper as [42]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
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
Kopelman, P. G. (2000) · Nature · doi:10.1038/35007508 · Cited by 4,795
Subcutaneous and visceral adipose tissue: their relation to the metabolic syndrome
Wajchenberg, B. L. (2000) · Endocrine Reviews · doi:10.1210/edrv.21.6.0415 · Cited by 2,961
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
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
Self-citationChronic 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
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
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
Decreasing 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
Intranasal insulin improves memory in humans
Benedict, C., Hallschmid, M., Hatke, A., Schultes, B., Fehm, H. L., Born, J., & Kern, W. (2004) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2004.04.003 · Cited by 699
Self-citation
Cited by
Sorted by citations
Sex and Gender Differences in Risk, Pathophysiology and Complications of Type 2 Diabetes Mellitus
Kautzky-Willer, A., Harreiter, J., & Pacini, G. (2016) · Endocrine Reviews · doi:10.1210/er.2015-1137 · Cited by 2,043
Sex differences in metabolic homeostasis, diabetes, and obesity
Mauvais-Jarvis, F. (2015) · Biology of Sex Differences · doi:10.1186/s13293-015-0033-y · Cited by 626
“Indeed, intranasal insulin—which reaches the brain directly along olfactory perivascular channels—reduces body fat in men but not in women [33].”
BackgroundBrain 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
“Eight weeks of intranasal insulin treatment reduced body weight and body fat content in healthy men but not in women (144), whereas obese men did not lose body fat during intranasal insulin treatment but still showed improved declarative memory performance (FIGURE 8) (143).”
BackgroundSelf-citationPower, M. L., & Schulkin, J. A. (2007) · British Journal Of Nutrition · doi:10.1017/s0007114507853347 · Cited by 645
“Intranasal insulin reduced feelings of hunger in men but not in women((49)).”
Gonadal Hormones Determine Sensitivity to Central Leptin and Insulin
Clegg, D. J., Brown, L. M., Woods, S. C., & Benoit, S. C. (2006) · Diabetes · doi:10.2337/diabetes.55.04.06.db05-1339 · Cited by 552
“We previously reported that the brain of male rats is relatively more sensitive to the catabolic action of insulin, whereas the brain of female rats is relatively more sensitive to the catabolic action of leptin (35,36); analogous data have recently been reported for humans (37).”
Sex differences in the physiology of eating
Asarian, L., & Geary, N. (2013) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00446.2012 · Cited by 513
Freiherr, J., Hallschmid, M., Frey, W. H., Brünner, Y. F., Chapman, C. D., Hölscher, C., Craft, S., Felice, F. G. D., & Benedict, C. (2013) · CNS Drugs · doi:10.1007/s40263-013-0076-8 · Cited by 477
Self-citationCentral Control of Body Weight and Appetite
Woods, S. C., & D’Alessio, D. A. (2008) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2008-1630 · Cited by 477
“Alternatively, there are reports that some formulations of nasally administered insulin elicit reduced food intake and body weight in humans without altering plasma glucose (184, 185).”
BackgroundCentral insulin action in energy and glucose homeostasis
Plum, L. (2006) · Journal of Clinical Investigation · doi:10.1172/jci29063 · Cited by 444
Intranasal Treatment of Central Nervous System Dysfunction in Humans
Chapman, C. D., Frey, W. H., Craft, S., Danielyan, L., Hallschmid, M., Schiöth, H. B., & Benedict, C. (2013) · Pharmaceutical Research · doi:10.1007/s11095-012-0915-1 · Cited by 310
Self-citationBenedict, C., Kern, W., Schultes, B., Born, J., & Hallschmid, M. (2008) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2007-2606 · Cited by 296
“intranasal insulin administration decreased body weight and body fat in men but not in women (12).”
BackgroundResultSelf-citationInsulin in the Brain: Sources, Localization and Functions
Ghasemi, R., Haeri, A., Dargahi, L., Mohamed, Z., & Ahmadiani, A. (2012) · Molecular Neurobiology · doi:10.1007/s12035-012-8339-9 · Cited by 308
“Whereas prolonged intranasal insulin causes weight loss in men, it induces elevation of water storage and weight gain in women [122].”
BackgroundPancreatic signals controlling food intake; insulin, glucagon and amylin
Woods, S. C., Lutz, T. A., Geary, N., & Langhans, W. (2006) · Philosophical Transactions of the Royal Society B Biological Sciences · doi:10.1098/rstb.2006.1858 · Cited by 301
“Humans receiving insulin in this way eat less food and lose body fat (Hallschmid et al. 2004a,b).”
CNS leptin and insulin action in the control of energy homeostasis
Belgardt, B., & Brüning, J. C. (2010) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2010.05799.x · Cited by 287
The brain as an insulin-sensitive metabolic organ
Milstein, J. L., & Ferris, H. A. (2021) · Molecular Metabolism · doi:10.1016/j.molmet.2021.101234 · Cited by 274
“However, one study that treated patients with intranasal insulin for 8 weeks found that while men lost body fat with the treatment, women did not [93].”
BackgroundSex differences in the regulation of body weight
Shi, H., & Clegg, D. J. (2009) · Physiology & Behavior · doi:10.1016/j.physbeh.2009.02.017 · Cited by 271
“recent human study showing that men, but not women, lose body weight, body fat and waist circumference following intranasal insulin administration [53].”
BackgroundNeuronal control of peripheral insulin sensitivity and glucose metabolism
Ruud, J., Steculorum, S. M., & Brüning, J. C. (2017) · Nature Communications · doi:10.1038/ncomms15259 · Cited by 245
Impaired 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
Marks, D. R., Tucker, K., Cavallin, M. A., Mast, T. G., & Fadool, D. A. (2009) · The Journal of Neuroscience · doi:10.1523/jneurosci.1350-09.2009 · Cited by 242
“Most glucose transport into the CNS is not dependent on insulin, and the poor correlation of insulin receptor location and neuron energy utilization suggest that insulin has different regulatory roles in the brain over that of the periphery (Brüning et al., 2000; Hallschmid et al., 2004).”
Sexual differences in the control of energy homeostasis
Shi, H., Seeley, R. J., & Clegg, D. J. (2009) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2009.03.004 · Cited by 242
“Comparable phenomenon has been reported in a recent human study that men, but not women, lose body weight, body fat and waist circumference following intranasal insulin administration [65], an approach that increases insulin concentration of the cerebrospinal fluid and thereby alters brain functions [24].”
BackgroundHigh-fat feeding promotes obesity via insulin receptor/PI3K-dependent inhibition of SF-1 VMH neurons
Klöckener, T., Heß, S., Belgardt, B., Paeger, L., Verhagen, L. A. W., Husch, A., Sohn, J., Hampel, B., Dhillon, H., Zigman, J. M., et al. (2011) · Nature Neuroscience · doi:10.1038/nn.2847 · Cited by 247
“and insulin can acutely suppress food intake and decreases fat mass in both rodents and human”
BackgroundCentral 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
Insulin regulates astrocyte gliotransmission and modulates behavior
Cai, W., Xue, C., Sakaguchi, M., Konishi, M., Shirazian, A., Ferris, H. A., Li, M. E., Yu, R., Kleinridders, A., Pothos, E. N., et al. (2018) · Journal of Clinical Investigation · doi:10.1172/jci99366 · Cited by 229
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
Claxton, A., Baker, L. D., Wilkinson, C. W., Trittschuh, E. H., Chapman, D., Watson, G. S., Cholerton, B., Plymate, S. R., Arbuckle, M., & Craft, S. (2013) · Journal of Alzheimer’s Disease · doi:10.3233/jad-122308 · Cited by 215
“This is an important finding, as several studies administering ICV insulin to rats [19] and intranasal insulin to healthy young adults have found insulin to have an anorexigenic effect, especially for men [20, 21].”
Control of energy homeostasis by insulin and leptin: Targeting the arcuate nucleus and beyond
Könner, A. C., Klöckener, T., & Brüning, J. C. (2009) · Physiology & Behavior · doi:10.1016/j.physbeh.2009.03.027 · Cited by 230
“a signal related to the amount of body fat and causes a long-term, net catabolic response, decreasing food intake and increasing energy expenditure [2–5].”
BackgroundBrain 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
The endocrinology of food intake
Begg, D. P., & Woods, S. C. (2013) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2013.136 · Cited by 214
Brain insulin, energy and glucose homeostasis; genes, environment and metabolic pathologies
Gerozissis, K. (2008) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2008.01.050 · Cited by 204
“However, studies in humans show that overweight subjects, in particular female patients, are resistant to this treatment (Hallschmid et al., 2004; Fehm et al., 2006).”
BackgroundHallschmid, M., Higgs, S., Thienel, M., Ott, V., & Lehnert, H. (2012) · Diabetes · doi:10.2337/db11-1390 · Cited by 181
Self-citationIntranasal Insulin for Alzheimer’s Disease
Hallschmid, M. (2021) · CNS Drugs · doi:10.1007/s40263-020-00781-x · Cited by 188
“Although experimental indicators of a preponderance of metabolic effects of IN insulin in men rather than women [62, 69] buttress the assumption of a sex difference in the functional response to IN insulin, studies in larger samples of male and female participants with cognitive impairments have only yielded sporadic…”
BackgroundSelf-citationInsulin 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
Kullmann, S., Heni, M., Veit, R., Scheffler, K., Machann, J., Häring, H.-U., Fritsche, A., & Preissl, H. (2015) · Diabetes Care · doi:10.2337/dc14-2319 · Cited by 175
Insulin controls food intake and energy balance via NPY neurons
Loh, K., Zhang, L., Brandon, A. E., Wang, Q., Begg, D. P., Qi, Y., Fu, M., Kulkarni, R. N., Teo, J. D., Baldock, P. A. J., et al. (2017) · Molecular Metabolism · doi:10.1016/j.molmet.2017.03.013 · Cited by 173
Intranasal Insulin to Improve Memory Function in Humans
Benedict, C., Hallschmid, M., Schultes, B., Jan Born, A., & Kern, W. (2007) · Neuroendocrinology · doi:10.1159/000106378 · Cited by 171
“Accordingly, circulating insulin and glucose levels also do not change during prolonged (8 weeks) of intranasal treatment with insulin (160 IU/day) [”
BackgroundSelf-citationBrain Insulin Signaling and Alzheimer's Disease: Current Evidence and Future Directions
Schiöth, H. B., Craft, S., Brooks, S. J., Frey, W. H., & Benedict, C. (2011) · Molecular Neurobiology · doi:10.1007/s12035-011-8229-6 · Cited by 168
“, [9–11]).”
Self-citationObese 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
Self-citationIntranasal Insulin Suppresses Food Intake via Enhancement of Brain Energy Levels in Humans
Jauch‐Chara, K., Friedrich, A., Rezmer, M., Melchert, U. H., Scholand-Engler, H. G., Hallschmid, M., & Oltmanns, K. M. (2012) · Diabetes · doi:10.2337/db12-0025 · Cited by 163
“The dosage of intranasal insulin used here (40 IU) is the lowest dosage that has previously been shown to reduce body weight (8) and to double the insulin”
Self-citationThe selfish brain: competition for energy resources
Fehm, H. L., Kern, W., & Peters, A. (2006) · Progress in brain research · doi:10.1016/s0079-6123(06)53007-9 · Cited by 168
Self-citationIntranasal insulin as a therapeutic option in the treatment of cognitive impairments
Benedict, C., Frey, W. H., Schiöth, H. B., Schultes, B., Jan Born, A., & Hallschmid, M. (2010) · Experimental Gerontology · doi:10.1016/j.exger.2010.08.026 · Cited by 165
“…has been shown in a number of different species including humans that enhanced brain insulin signaling decreases food intake and body weight, pointing to an important physiological role of the hormone in the CNS [(Woods et al., 1979; Hallschmid et al., 2004a), for review, see (Porte et al., 2005)].”
Self-citationHypogonadotropic Hypogonadism in Men With Diabesity
Dhindsa, S., Ghanim, H., Batra, M., & Dandona, P. (2018) · Diabetes Care · doi:10.2337/dc17-2510 · Cited by 162
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
Self-citationSexual Dimorphism in Body Fat Distribution and Risk for Cardiovascular Diseases
Nedungadi, T. P., & Clegg, D. J. (2009) · Journal of Cardiovascular Translational Research · doi:10.1007/s12265-009-9101-1 · Cited by 154
“A comparable phenomenon has been reported in a recent study in humans, suggesting that men lose more body weight and body fat and change their waist circumference following intranasal insulin administration when compared to women [ 61 ].”
ResultLimited Alzheimer-type neurodegeneration in experimental obesity and type 2 diabetes mellitus
Moroz, N., Tong, M., Longato, L., Xu, H., & de la Monte, S. M. (2008) · Journal of Alzheimer s Disease · doi:10.3233/jad-2008-15103 · Cited by 151
“In addition, treatment with intranasal insulin [2,3,23,24],and/or insulin sensitizer agents such as peroxisome proliferator activated receptor agonists [14,30,57] which has demonstrated ability to increase memory and cognitive function, may also be beneficial in reducing cognitive dysfunction in…”
Peripheral Hyperinsulinemia Promotes Tau Phosphorylation In Vivo
Freude, S., Plum, L., Schnitker, J., Leeser, U., Udelhoven, M., Krone, W., Brüning, J. C., & Schubert, M. (2005) · Diabetes · doi:10.2337/diabetes.54.12.3343 · Cited by 147
“(19) showed that in male normal weight subjects, intranasal insulin exerts catabolic effects on body weight and obesity.”
BackgroundOtt, 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
“by promoting weight gain in the form of muscle and fat mass [73,74], IN and ICV insulin administration in humans and animals, respectively, induces catabolic effects by reducing food intake [19,23] and as a consequence body fat content [20,21] particularly in the male organism [21–23].”
BackgroundSelf-citationBrain 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
“This phenomenon was first observed in overweight persons, who not only appeared to be resistant to brain insulin actions in terms of regional brain activity but also with regard to many functional consequences: While insulin in the brain influences food intake and body weight [217, 219] in lean persons, no such effect…”
BackgroundBenedict, C., Brede, S., Schiöth, H. B., Lehnert, H., Schultes, B., Born, J., & Hallschmid, M. (2011) · Diabetes · doi:10.2337/db10-0329 · Cited by 129
“Notably, intranasal insulin reduces food intake (9) and body fat content (10) in healthy men, indicating that following intranasal administration, the hormone accesses neuronal networks relevant for energy homeostasis.”
BackgroundSelf-citationInsulin, Aging, and the Brain: Mechanisms and Implications
Akintola, A. A., & van Heemst, D. (2015) · Frontiers in Endocrinology · doi:10.3389/fendo.2015.00013 · Cited by 130
“Sub-chronic intranasal insulin application in humans was shown to decrease food intake and weight gain (92) in healthy young men, and to improve declarative memory and mood (173).”
BackgroundObesity – A neuropsychological disease? Systematic review and neuropsychological model
Jauch‐Chara, K., & Oltmanns, K. M. (2014) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2013.12.001 · Cited by 136
The selfish brain: Competition for energy resources
Peters, A. (2010) · American Journal of Human Biology · doi:10.1002/ajhb.21106 · Cited by 121
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
“This phenomenon was first observed in overweight people, who appeared to be resistant to brain insulin action not only in terms of regional brain activity but also with regard to many functional consequences: whereas insulin in the brain influences food intake and body weight (1,3) in lean people, no such effects have…”
BackgroundInsulin resistance: sex matters
Mittendorfer, B. (2005) · Current Opinion in Clinical Nutrition & Metabolic Care · doi:10.1097/01.mco.0000172574.64019.98 · Cited by 113
Strategies for Intranasal Delivery of Therapeutics for the Prevention and Treatment of NeuroAIDS
Hanson, L. R., & Frey, W. H. (2006) · Journal of Neuroimmune Pharmacology · doi:10.1007/s11481-006-9039-x · Cited by 111
“On a side note, intranasal insulin has also been shown to reduce body fat in normal, but not obese men (Hallschmid et al. 2004, 2006).”
BackgroundHallschmid, M. (2021) · Journal of Neuroendocrinology · doi:10.1111/jne.12934 · Cited by 113
Self-citationKullmann, 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
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-citationCan Nasal Drug Delivery Bypass the??Blood-Brain Barrier?
Merkus, F. W. H. M., & van den Berg, M. P. (2007) · Drugs in R&D · doi:10.2165/00126839-200708030-00001 · Cited by 109
Dash, S., Xiao, C., Morgantini, C., Koulajian, K., & Lewis, G. F. (2015) · Diabetes · doi:10.2337/db14-0685 · Cited by 108
“In addition, 8 weeks of INI treatment in slim healthy volunteers modestly reduced fat mass and body weight in men; modest weight gain occurred in women, which is thought to be due to an increase in extracellular water, but, importantly, there was no change in body fat (19).”
BackgroundEffects of intranasal hypocretin-1 (orexin A) on sleep in narcolepsy with cataplexy
Baier, P. C., Hallschmid, M., Seeck-Hirschner, M., Weinhold, S. L., Burkert, S., Diessner, N., Göder, R., Aldenhoff, J., & Hinze‐Selch, D. (2011) · Sleep Medicine · doi:10.1016/j.sleep.2011.06.015 · Cited by 103
“Timing and dosing were chosen according to previous experiments on the intranasal administration of neuropeptides performed by our group [29–31] and were also based on results of animal experiments on the intranasal administration of hcrt-1 [21,32].”
BackgroundMethodSelf-citationRegulation of the mesolimbic dopamine circuit by feeding peptides
Liu, S., & Borgland, S. L. (2015) · Neuroscience · doi:10.1016/j.neuroscience.2014.12.046 · Cited by 104
“Intra-cerebroventricular (icv) injection of insulin or intranasal application of insulin decreases food intake and bodyweight in rodents and primates (Woods et al., 1979; Chavez et al., 1995; Hallschmid et al., 2004; Brown et al., 2006).”
Intranasal insulin in Alzheimer's disease: Food for thought
Chapman, C. D., Schiöth, H. B., Grillo, C. A., & Benedict, C. (2017) · Neuropharmacology · doi:10.1016/j.neuropharm.2017.11.037 · Cited by 111
“…reduces body fat, alters CNS processing of food cues, results in lower ad-libitum food intake, and improves peripheral insulin signaling in humans (Hallschmid et al., 2004b; Benedict et al., 2008, 2011; Guthoff et al., 2010; Hallschmid et al., 2012; Jauch-Chara et al., 2012; Iwen et al., 2014).”
Self-citationMayer, C., & Belsham, D. D. (2009) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2009.02.031 · Cited by 103
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
“appetite and body weight [67], suppression of systemic lipolysis [68], and improved hepatic energy metabolism [69].”
BackgroundBenedict, C., & Grillo, C. A. (2018) · Frontiers in Neuroscience · doi:10.3389/fnins.2018.00215 · Cited by 101
“…function of insulin receptors ranges from regulation of whole-body energy metabolism in the hypothalamus (Woods et al., 1979; Brief and Davis, 1984; Hallschmid et al., 2004; Grillo et al., 2007; Benedict et al., 2011; Thienel et al., 2017) to modulation of memory at hippocampal level (Park et al.,…”
BackgroundSelf-citationNon-Invasive Strategies for Nose-to-Brain Drug Delivery.
Ja, T., Quispe, R. C., Khan, F. A., & Новак (2020) · PubMed · Cited by 114
New Twist on Neuronal Insulin Receptor Signaling in Health, Disease, and Therapeutics
Wada, A., Yokoo, H., Yanagita, T., & Kobayashi, H. (2005) · Journal of Pharmacological Sciences · doi:10.1254/jphs.crj05006x · Cited by 95
Insulin Promotes Neuronal Survival via the Alternatively Spliced Protein Kinase CδII Isoform
Apostolatos, A. H., Song, S., Acosta, S., Peart, M. S., Watson, J. E., Bickford, P. C., Cooper, D. R., & Patel, N. A. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.313080 · Cited by 99
Evans, J. J., & Anderson, G. M. (2012) · Human Reproduction Update · doi:10.1093/humupd/dms004 · Cited by 101
Wu, H., Zhou, Y., Wang, Y., Tong, L., Wang, F., Song, S., Xu, L., Liu, B., Yan, H., & Sun, Z. (2021) · Frontiers in Pharmacology · doi:10.3389/fphar.2021.717192 · Cited by 90
Hallschmid, M., & Schultes, B. (2009) · Diabetologia · doi:10.1007/s00125-009-1501-x · Cited by 90
“In normal-weight men, intranasal insulin administration for 8 weeks has been shown to reduce body fat, serum leptin levels and waist circumference as compared with placebo treatment [17].”
BackgroundSelf-citationBohringer, A., Schwabe, L., Richter, S., & Schachinger, H. (2008) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2008.08.002 · Cited by 89
“In humans, intranasal insulin administration is an easy applicable tool for analyzing central nervous insulin effects (Fehm et al., 2000; Hallschmid et al., 2004).”
Repetitive electric brain stimulation reduces food intake in humans
Jauch‐Chara, K., Kistenmacher, A., Herzog, N., Schwarz, M., Schweiger, U., & Oltmanns, K. M. (2014) · American Journal of Clinical Nutrition · doi:10.3945/ajcn.113.075481 · Cited by 88
Glucocorticoids, stress and eating: The mediating role of appetite‐regulating hormones
Kuckuck, S., van der Valk, E. S., Scheurink, A. J. W., van der Voorn, B., Iyer, A. M., Visser, J. A., Delhanty, P. J. D., van den Berg, S. A. A., & van Rossum, E. F. C. (2022) · Obesity Reviews · doi:10.1111/obr.13539 · Cited by 99
Intranasal insulin therapy for cognitive impairment and neurodegeneration: current state of the art
de la Monte, S. M. (2013) · Expert Opinion on Drug Delivery · doi:10.1517/17425247.2013.856877 · Cited by 89
“Besides increasing cognitive performance, chronic intranasal insulin administration reduces adiposity in normal individuals [69].”
Testosterone deficiency in men with Type 2 diabetes: pathophysiology and treatment
Gianatti, E., & Grossmann, M. (2019) · Diabetic Medicine · doi:10.1111/dme.13977 · Cited by 86
Mayer, C., & Belsham, D. D. (2009) · Endocrinology · doi:10.1210/en.2009-0838 · Cited by 84
Food Cues and Obesity: Overpowering Hormones and Energy Balance Regulation
Belfort-DeAguiar, R., & Seo, D. (2018) · Current Obesity Reports · doi:10.1007/s13679-018-0303-1 · Cited by 84
Jastreboff, A. M., Lacadie, C., Seo, D., Kubat, J., Van Name, M. A., Giannini, C., Savoye, M., Constable, R. T., Sherwin, R. S., Caprio, S., et al. (2014) · Diabetes Care · doi:10.2337/dc14-0525 · Cited by 83
Schilling, T. M., de Sá, D. S. F., Westerhausen, R., Strelzyk, F., Larra, M. F., Hallschmid, M., Savaskan, E., Oitzl, M. S., Busch, H., Naumann, E., et al. (2013) · Human Brain Mapping · doi:10.1002/hbm.22304 · Cited by 84
“The lack of differences in hunger ratings is according to previous research where hunger was assessed after acute application of intranasal insulin [Benedict et al., 2008; Hallschmid et al., 2004b; Jauch-Chara et al., 2012].”
BackgroundResultSelf-citationYang, W., Jiang, W., & Guo, S. (2023) · Nutrients · doi:10.3390/nu15214671 · Cited by 97
“Chronically daily intranasal insulin administration for 8 weeks decreases body weight and adiposity in healthy men [43].”
BackgroundGastrointestinal hormones: the regulation of appetite and the anorexia of ageing
Moss, C., Dhillo, W. S., Frost, G. S., & Hickson, M. (2011) · Journal of Human Nutrition and Dietetics · doi:10.1111/j.1365-277x.2011.01211.x · Cited by 89
Effects of Intranasal Insulin on Hepatic Fat Accumulation and Energy Metabolism in Humans
Gancheva, S., Koliaki, C., Bierwagen, A., Nowotny, P., Heni, M., Fritsche, A., Häring, H.-U., Szendroedi, J., & Roden, M. (2015) · Diabetes · doi:10.2337/db14-0892 · Cited by 81
“Intranasally administered insulin may further affect body weight and fat content (11).”
BackgroundGLP-1 receptor agonists show neuroprotective effects in animal models of diabetes
Gault, V. A., & Hölscher, C. (2018) · Peptides · doi:10.1016/j.peptides.2017.11.017 · Cited by 83
“Insulin not only controls glucose utilization in the periphery (Hallschmid et al., 2004; Benedict et al., 2011; Hallschmid et al., 2012; Ott et al., 2012), but has additional roles in the brain.”
Neuroanatomical Framework of the Metabolic Control of Reproduction
Hill, J. W., & Elias, C. F. (2018) · Physiological Reviews · doi:10.1152/physrev.00033.2017 · Cited by 80
“Intracerebroventricular or intranasal application of insulin decreases body weight and food intake in rats, mice, and primates, including humans (55, 74, 190, 496).”
BackgroundYu, I.-C. I., Lin, H., Liu, N.-C., Sparks, J. D., Yeh, S., Fang, L., Chen, L., & Chang, C. (2012) · Diabetes · doi:10.2337/db12-0135 · Cited by 79
“Analogous studies have been reported for humans using an intranasal route of insulin delivery, showing that men, but not women, decrease body weight and body fat after 8 weeks of intranasal insulin (14).”
BackgroundHallschmid, M., Benedict, C., Jan Born, A., Fehm, H., & Kern, W. (2004) · Physiology & Behavior · doi:10.1016/j.physbeh.2004.07.023 · Cited by 77
Self-citationKrug, R., Benedict, C., Jan Born, A., & Hallschmid, M. (2010) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2010-0744 · Cited by 74
Self-citationCentral Insulin Administration Improves Odor-Cued Reactivation of Spatial Memory in Young Men
Brünner, Y. F., Kofoet, A., Benedict, C., & Freiherr, J. (2015) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2014-3018 · Cited by 68
Self-citationTargeting Intermediary Metabolism in the Hypothalamus as a Mechanism to Regulate Appetite
Lopaschuk, G. D., Ussher, J. R., & Jaswal, J. S. (2010) · Pharmacological Reviews · doi:10.1124/pr.109.002428 · Cited by 71
“Indeed, previous reports demonstrate the ability of exogenously administered insulin to decrease appetite and food intake in rodents, nonhuman primates, and humans (Woods et al., 1979, 1984; Ikeda et al., 1986; McGowan et al., 1993; Hallschmid et al., 2004).”
BackgroundNeuronal systems and circuits involved in the control of food intake and adaptive thermogenesis
Caron, A., & Richard, D. (2016) · Annals of the New York Academy of Sciences · doi:10.1111/nyas.13263 · Cited by 69
Broadening the definition of brain insulin resistance in aging and Alzheimer's disease
Frazier, H. N., Ghoweri, A. O., Anderson, K. L., Lin, R., Porter, N. M., & Thibault, O. (2018) · Experimental Neurology · doi:10.1016/j.expneurol.2018.12.007 · Cited by 69
“With respect to the impact on feeding behavior, women appeared to gain more weight during an 8-week trial compared to men (Hallschmid et al., 2004).”
High 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
“In a study with twice daily nasal insulin use, body weight and body fat were reduced after 8 weeks [13].”
Hallschmid, M., Jauch-Chara, K., Korn, O., Mölle, M., Rasch, B., Born, J., Schultes, B., & Kern, W. (2010) · Diabetes · doi:10.2337/db09-1493 · Cited by 61
“Experimental administration of insulin to the central nervous system (CNS) inhibits food intake and reduces body fat content in animals (3,4) and humans (5,6), suggesting that circulating insulin provides negative, anorexigenic feedback on the amount of body fat to the brain.”
BackgroundSelf-citationBegg, D. P., & Woods, S. C. (2013) · AJP Advances in Physiology Education · doi:10.1152/advan.00167.2012 · Cited by 63
“With the use of an intranasal insulin administration technique to increase CSF insulin levels, a dose-dependent reduction of food intake was observed in human volunteers (58), and daily treatment resulted in significant weight loss after 6 wk (58).”
MethodObesity-induced increases in sympathetic nerve activity: Sex matters
Brooks, V. L., Shi, Z., Holwerda, S. W., & Fadel, P. J. (2014) · Autonomic Neuroscience · doi:10.1016/j.autneu.2014.11.006 · Cited by 61
“, 2003) or intranasal administration in humans (Hallschmid et al., 2004; Benedict et al., 2008; Krug et al., 2010), decreases food intake in males, but notably not in females.”
Smith, C. E., Mollard, R. C., Luhovyy, B. L., & Anderson, G. H. (2012) · British Journal Of Nutrition · doi:10.1017/s0007114512000700 · Cited by 63
“The same relationships have been confirmed in humans (Hallschmid et al. 2004a; Hallschmid et al. 2004b).”
BackgroundThe 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 62
The Insulin-Mediated Modulation of Visually Evoked Magnetic Fields Is Reduced in Obese Subjects
Guthoff, M., Stingl, K. T., Tschritter, O., Vidaković, M. R., Heni, M., Štingl, K., Hallschmid, M., Häring, H., Fritsche, A., Preissl, H. T., et al. (2011) · PLoS ONE · doi:10.1371/journal.pone.0019482 · Cited by 59
“[20] showed that intranasal insulin reduced body fat in men but not in women, a limitation of our study is that we used more female than male subjects.”
MethodResultSelf-citationIntranasal Insulin Reduces Olfactory Sensitivity in Normosmic Humans
Brünner, Y. F., Benedict, C., & Freiherr, J. (2013) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2013-2061 · Cited by 58
Self-citation
Metadata
- Authors
- Hallschmid, M., Benedict, C., Schultes, B., Fehm, H.-L., Born, J., & Kern, W.
- Affiliations
- University of Lübeck (DE)
- Institute of Neuroendocrinology, University of Lübeck, Lübeck, Germany
- Venue
- Diabetes
- Publisher
- American Diabetes Association
- Published
- 2004-11-01
- Volume
- 53
- Issue
- 11
- Pages
- 3024-3029
- ISSN
- 0012-1797 (ISSN-L)
- 1939-327X
- OpenAlex
- W2157247104
- Cited by
- 281
- References
- 32
- Citations by year
- 2026: 7 · 2025: 9 · 2024: 7 · 2023: 8 · 2022: 10 · 2021: 14 · 2020: 9 · 2019: 12 · 2018: 20 · 2017: 11 · 2016: 16 · 2015: 17 · 2014: 10 · 2013: 24 · 2012: 21
- FWCI
- 3.95
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Diabetes (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
- intranasal insulin, fat loss, sex differences, leptin, waist circumference, plasma leptin, extracellular water, weight loss
- MeSH terms
- Adipose Tissue, Administration, Intranasal, Body Weight, Extracellular Space, Female, Humans, Insulin, Male, Placebos, Reference Values, Sex Characteristics, Body Mass Index
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
