Saturable transport of insulin from plasma into the central nervous system of dogs in vivo. A mechanism for regulated insulin delivery to the brain.
Open accessAbstract
By acting in the central nervous system, circulating insulin may regulate food intake and body weight. We have previously shown that the kinetics of insulin uptake from plasma into cerebrospinal fluid (CSF) can best be explained by passage through an intermediate compartment. To determine if transport kinetics into this compartment were consistent with an insulin receptor-mediated transport process, we subjected overnight fasted, anesthetized dogs to euglycemic intravenous insulin infusions for 90 min over a wide range of plasma insulin levels (69-5,064 microU/ml) (n = 10). Plasma and CSF samples were collected over 8 h for determination of immunoreactive insulin levels, and the kinetics of insulin uptake from plasma into CSF were analyzed using a compartmental model with three components (plasma-->intermediate compartment-->CSF). By sampling frequently during rapid changes of plasma and CSF insulin levels, we were able to precisely estimate three parameters (average standard deviation 14%) characterizing the uptake of insulin from plasma, through the intermediate compartment and into CSF (k1k2); insulin entry into CSF and insulin clearance from the intermediate compartment (k2 + k3); and insulin clearance from CSF (k4). At physiologic plasma insulin levels (80 +/- 7.4 microU/ml), k1k2 was determined to be 10.7 x 10(-6) +/- 1.3 x 10(-6) min-2. With increasing plasma levels, however, k1k2 decreased progressively, being reduced sevenfold at supraphysiologic levels (5,064 microU/ml). The apparent KM of this saturation curve was 742 microU/ml (approximately 5 nM). In contrast, the rate constants for insulin removal from the intermediate compartment and from CSF did not vary with plasma insulin (k2 + k3 = 0.011 +/- 0.0019 min-1 and k4 = 0.046 +/- 0.021 min-1). We conclude that delivery of plasma insulin into the central nervous system is saturable, and is likely facilitated by an insulin-receptor mediated transport process.
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Insulin transport from brain blood to brain mass or to CSF follows the Michaelis-Menten equation mathematically.
“Like that of glucose, insulin transport from brain blood to brain mass or to CSF also follows the Michaelis-Menten equation mathematically, on account of the analogous blood-brain barrier transport systems existing for glucose, amino acids, plasma proteins, as well as the circulating insulin [29].”
From A mathematical model of brain glucose homeostasis (2009) · cites this paper as [29]
The section on estimating KM fits the saturable component of insulin uptake from plasma toward CSF with a variation of the Michaelis–Menten equation. It also identifies a separate, linear nonspecific component. The Discussion describes uptake into an intermediate compartment, hypothesized to occur across the blood–brain barrier, but does not establish that transport into brain mass itself follows that equation. (LLM, conf=0.85)
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Cites
Morgan, C. R., & Lazarow, A. (1963) · Diabetes · doi:10.2337/diab.12.2.115 · Cited by 2,212 · see citing works
Chronic intracerebroventricular infusion of insulin reduces food intake and body weight of baboons
Woods, S. C., Lotter, E. C., McKay, L. D., & Porte, D. (1979) · Nature · doi:10.1038/282503a0 · Cited by 1,114 · see citing works
Self-citationInsulin in the Brain: A Hormonal Regulator of Energy Balance*
Schwartz, M. W., Figlewicz, D. P., Baskin, D. G., Woods, S. C., & Porte, D. (1992) · Endocrine Reviews · doi:10.1210/edrv-13-3-387 · Cited by 808 · see citing works
Self-citationReceptor‐mediated transcytosis of transferrin across the blood‐brain barrier
Fishman, J. B., Rubin, J. B., Handrahan, J. V., Connor, J. R., & Fine, R. E. (1987) · Journal of Neuroscience Research · doi:10.1002/jnr.490180206 · Cited by 545 · see citing works
Receptor-Mediated Transport of Insulin Across Endothelial Cells
King, G. L., & Johnson, S. M. (1985) · Science · doi:10.1126/science.3883490 · Cited by 474 · see citing works
Facilitated transfer of glucose from blood into brain tissue.
Crone, C. G. (1965) · The Journal of Physiology · doi:10.1113/jphysiol.1965.sp007748 · Cited by 443 · see citing works
Blood-brain barrier transcytosis of insulin in developing rabbits
Duffy, K. R., & Pardridge, W. M. (1987) · Brain Research · doi:10.1016/0006-8993(87)90236-8 · Cited by 358 · see citing works
The mathematical modeling of metabolic and endocrine systems
Twizell, E. H. (1984) · Applied Mathematical Modelling · doi:10.1016/0307-904x(84)90183-5 · Cited by 329 · see citing works
Optimal sampling times for pharmacokinetic experiments
D’Argenio, D. Z. (1981) · Journal of Pharmacokinetics and Biopharmaceutics · doi:10.1007/bf01070904 · Cited by 324 · see citing works
Receptor-Mediated Peptide Transport through the Blood-Brain Barrier*
Pardridge, W. M. (1986) · Endocrine Reviews · doi:10.1210/edrv-7-3-314 · Cited by 316 · see citing works
Insulin transport across capillaries is rate limiting for insulin action in dogs.
Yang, Y. J., Hope, I. D., Ader, M., & Bergman, R. N. (1989) · Journal of Clinical Investigation · doi:10.1172/jci114339 · Cited by 303 · see citing works
Self-citationThe Dose—Response Relation in Pharmacology
Tallarida, R. J., & Jacob, L. S. (1979) · Springer eBooks · doi:10.1007/978-1-4684-6265-4 · Cited by 277 · see citing works
Cerebrospinal Fluid Insulin Levels Increase During Intravenous Insulin Infusions in Man*
Wallum, B. J., Taborsky, G. J., Porte, D., Figlewicz, D. P., Jacobson, L., Beard, J. C., Ward, W. K., & Dorsa, D. M. (1987) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem-64-1-190 · Cited by 254 · see citing works
Self-citationGabel, R. A., & Roberts, R. A. (1973) · CERN Document Server (European Organization for Nuclear Research) · Cited by 223 · see citing works
Insulin in the brain: a hormonal regulator of energy balance
Schwartz, M. W. (1992) · Endocrine Reviews · doi:10.1210/er.13.3.387 · Cited by 201 · see citing works
Self-citationKinetics and specificity of insulin uptake from plasma into cerebrospinal fluid.
Schwartz, M. W., Sipols, A. J., Kahn, S. E., Lattemann, D. F., Taborsky, G. J., Bergman, R. N., Woods, S. C., & Porte, D. (1990) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.1990.259.3.e378 · Cited by 191 · see citing works
Self-citationSchwartz, M. W., Bergman, R. N., Kahn, S. E., Taborsky, G. J., Fisher, L. D., Sipols, A. J., Woods, S. C., Steil, G. M., & Porte, D. (1991) · Journal of Clinical Investigation · doi:10.1172/jci115431 · Cited by 183 · see citing works
Self-citationWoods, S., Porte, D., Bobbioni, E., Ionescu, E., Sauter, J., Rohner-Jeanrenaud, F., & Jeanrenaud, B. (1985) · The American Journal of Clinical Nutrition · doi:10.1093/ajcn/42.5.1063 · Cited by 180 · see citing works
Self-citationA Direct In Vitro Demonstration of Insulin Binding to Isolated Brain Microvessels
Frank, H. J. L., & Pardridge, W. M. (1981) · Diabetes · doi:10.2337/diab.30.9.757 · Cited by 164 · see citing works
Reed, D. J., & Woodbury, D. M. (1963) · The Journal of Physiology · doi:10.1113/jphysiol.1963.sp007298 · Cited by 139 · see citing works
Baskin, D. G., Woods, S. C., West, D. B., van Houten, M., Posner, B. I., Dorsa, D. M., & Porte, D. (1983) · Endocrinology · doi:10.1210/endo-113-5-1818 · Cited by 122 · see citing works
Self-citationTransport of Leucine‐Enkephalin Across the Blood‐Brain Barrier in the Perfused Guinea Pig Brain
Zloković, B. V., Lipovac, M. N., Begley, D. J., Davson, H., & Rakić, L. (1987) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.1987.tb03431.x · Cited by 118 · see citing works
McGowan, M. K., Andrews, K. M., Kelly, J., & Grossman, S. P. (1990) · Behavioral Neuroscience · doi:10.1037/0735-7044.104.2.373 · Cited by 109 · see citing works
Effect of Insulin on Glucose Uptake and Metabolism in the Human Placenta
Challier, J.-C., Hauguel, S., & Desmaizières, V. (1986) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem-62-5-803 · Cited by 103 · see citing works
Elevated insulin and satiety in obese and normal-weight rats
Vanderweele, D. A., Haraczkiewicz, E., & Itallie, T. B. V. (1982) · Appetite · doi:10.1016/s0195-6663(82)80003-2 · Cited by 73 · see citing works
A re-assessment of the regulation of adiposity and appetite by the brain insulin system.
Woods, S. C., Lattemann, D. F., Schwartz, M. W., & Porte, D. (1990) · PubMed · Cited by 57 · see citing works
Self-citationA direct in vitro demonstration of insulin binding to isolated brain microvessels
Frank, H. J., & Pardridge, W. M. (1981) · Diabetes · doi:10.2337/diabetes.30.9.757 · Cited by 57 · see citing works
Physiology of the cerebrospinal fluid
BETOURNE (1969) · Brain Research · doi:10.1016/0006-8993(69)90304-7 · Cited by 53 · see citing works
Yang, Y. J., Hope, I. D., Ader, M., Poulin, R. A., & Bergman, R. N. (1992) · Diabetes · doi:10.2337/diabetes.41.2.241 · Cited by 52 · see citing works
Self-citationVascular transport of insulin to rat cardiac muscle. Central role of the capillary endothelium.
Bar, R. S., Boes, M. K., & Sandra, A. (1988) · Journal of Clinical Investigation · doi:10.1172/jci113439 · Cited by 50 · see citing works
Insulin in the Central Nervous System
Yalow, R. S., & Eng, J. (1983) · Advances in metabolic disorders · doi:10.1016/b978-0-12-027310-2.50018-9 · Cited by 38 · see citing works
Insulin Binding to Brain Microvessels
Frank, H. J. L., & Pardridge, W. M. (1983) · Advances in metabolic disorders · doi:10.1016/b978-0-12-027310-2.50016-5 · Cited by 31 · see citing works
Ader, M., Poulin, R. A., Yang, Y. J., & Bergman, R. N. (1992) · Diabetes · doi:10.2337/diab.41.2.241 · Cited by 20 · see citing works
Self-citationInsulin transfer in the isolated human placenta.
Jm, K., & Js, K. (1968) · PubMed · Cited by 14 · see citing works
Neurochemical Aspects of Blood-Brain-Cerebrospinal Fluid Barriers
Cutler, R. W. P. (1980) · Springer eBooks · doi:10.1007/978-1-4684-1039-6_4 · Cited by 12 · see citing works
Metabolic clearance of insulin from the cerebrospinal fluid in the anesthetized rat
Manin, M., Broer, Y., Balage, M., Rostène, W. H., & Grizard, J. (1990) · Peptides · doi:10.1016/0196-9781(90)90102-b · Cited by 12 · see citing works
Flagged first, then by citations
Research works printed but not linked: 2
- Gilman, A. G., T. W. Rall, A. S. Nies, and P. Taylor, editors. 1990. Goodman and Gilman's The Pharmacological Basis ofTherapeutics. 8th edition. Pergamon Press, New York. 21.
- Novin, G. A. Bray, and W. Wyrwichka, editors. Raven Press, New York. 273- 280.
Cited by
Sorted by citations
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
Self-citationMechanisms 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 · see citing works
Brain insulin resistance in type 2 diabetes and Alzheimer disease: concepts and conundrums
Arnold, S. E., Arvanitakis, Z., Macauley-Rambach, S. L., Koenig, A. M., Wang, H.-Y., Ahima, R. S., Craft, S., Gandy, S., Buettner, C., Stoeckel, L. E., et al. (2018) · Nature Reviews Neurology · doi:10.1038/nrneurol.2017.185 · Cited by 1,597 · see citing works
Cerebrospinal fluid leptin levels: Relationship to plasma levels and to adiposity in humans
Schwartz, M. W., Peskind, E., Raskind, M., Boyko, E. J., & Porte, D. (1996) · Nature Medicine · doi:10.1038/nm0596-589 · Cited by 1,014 · see citing works
Self-citationTrends in insulin resistance: insights into mechanisms and therapeutic strategy
Li, M., Chi, X., Wang, Y., Setrerrahmane, S., Xie, W., & Xu, H. (2022) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-022-01073-0 · Cited by 939 · see citing works
The many faces of insulin-like peptide signalling in the brain
Fernandez, A. M., & Torres-Alemán, I. (2012) · Nature reviews. Neuroscience · doi:10.1038/nrn3209 · Cited by 872 · see citing works
Insulin and neurodegenerative disease: shared and specific mechanisms
Craft, S., & Stennis Watson, G. (2004) · The Lancet Neurology · doi:10.1016/s1474-4422(04)00681-7 · Cited by 830 · see citing works
Banks, W. A., Tschöp, M., Robinson, S. M., & Heiman, M. L. (2002) · The Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.102.034827 · Cited by 691 · see citing works
Blood–Brain Barrier Dysfunction as a Cause and Consequence of Alzheimer's Disease
Erickson, M. A., & Banks, W. A. (2013) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1038/jcbfm.2013.135 · Cited by 572 · see citing works
The Catabolic Action of Insulin in the Brain Is Mediated by Melanocortins
Benoit, S. C., Air, E. L., Coolen, L. M., Strauss, R., Jackman, A., Clegg, D. J., Seeley, R. J., & Woods, S. C. (2002) · The Journal of Neuroscience · doi:10.1523/jneurosci.22-20-09048.2002 · Cited by 417 · see citing works
Hormonal regulation of food intake
Stanley, S., Wynne, K., McGowan, B., & Bloom, S. (2005) · Physiological Reviews · doi:10.1152/physrev.00015.2004 · Cited by 372 · see citing works
Cytokine, sickness behavior, and depression
Dantzer, R. (2006) · Neurologic Clinics · doi:10.1016/j.ncl.2006.03.003 · Cited by 340 · see citing works
Differential Sensitivity to Central Leptin and Insulin in Male and Female Rats
Clegg, D. J., Riedy, C. A., Smith, K. A. B., Benoit, S. C., & Woods, S. C. (2003) · Diabetes · doi:10.2337/diabetes.52.3.682 · Cited by 332 · see citing works
Improving influence of insulin on cognitive functions in humans
Kern, W., Peters, A., Fruehwald-Schultes, B., Deininger, E., Born, J., & Fehm, H. L. (2001) · Neuroendocrinology · doi:10.1159/000054694 · Cited by 308 · see citing works
Modulation of memory by insulin and glucose: Neuropsychological observations in Alzheimer’s disease
Watson, G. S., & Craft, S. (2004) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2004.02.048 · Cited by 307 · see citing works
The role of dopamine in motivation for food in humans: implications for obesity
Wang, G.-J., Volkow, N. D., & Fowler, J. S. (2002) · Expert Opinion on Therapeutic Targets · doi:10.1517/14728222.6.5.601 · Cited by 285 · 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
Cognitive effects of insulin in the central nervous system
Park, C. R. (2001) · Neuroscience & Biobehavioral Reviews · doi:10.1016/s0149-7634(01)00016-1 · Cited by 270 · see citing works
Insulin and Leptin as Adiposity Signals
Benoit, S. C. (2004) · Recent Progress in Hormone Research · doi:10.1210/rp.59.1.267 · Cited by 266 · 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
Banks, W. A., Jaspan, J. B., & Kastin, A. J. (1997) · Peptides · doi:10.1016/s0196-9781(97)00198-8 · Cited by 219 · see citing works
Brain 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
Obesity, diabetes and the central nervous system
Porte Jr., D., Seeley, R. J., Woods, S. C., Baskin, D. G., Figlewicz, D. P., & Schwartz, M. W. (1998) · Diabetologia · doi:10.1007/s001250051002 · Cited by 186 · see citing works
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Obese men respond to cognitive but not to catabolic brain insulin signaling
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Intraventricular insulin and leptin reduce food intake and body weight in C57BL/6J mice
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Yuan, R., Meng, Q., Nautiyal, J., Flurkey, K., Tsaih, S.-W., Krier, R., Parker, M. G., Harrison, D. E., & Paigen, B. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1121113109 · Cited by 121 · see citing works
Rhea, E. M., Salameh, T. S., Gray, S., Niu, J., Banks, W. A., & Tong, J. (2018) · Molecular Metabolism · doi:10.1016/j.molmet.2018.09.007 · Cited by 114 · see citing works
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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
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- Authors
- Baura, G. D., Foster, D. M., Porte, D., Kahn, S. E., Bergman, R. N., Cobelli, C., & Schwartz, M. W.
- Affiliations
- University of Washington (US)
- University of Padua (IT)
- University of Southern California (US)
- Venue
- Journal of Clinical Investigation
- Published
- 1993-10-01
- Volume
- 92
- Issue
- 4
- Pages
- 1824-1830
- ISSN
- 0021-9738 (ISSN-L)
- PMC
- PMC288346
- OpenAlex
- W2135456335
- Cited by
- 489
- References
- 36
- Citations by year
- 2025: 7 · 2024: 9 · 2023: 8 · 2022: 11 · 2021: 18 · 2020: 15 · 2019: 14 · 2018: 18 · 2017: 25 · 2016: 21 · 2015: 22 · 2014: 22 · 2013: 27 · 2012: 18
- FWCI
- 3.35
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Investigation (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- U.S. Department of Veterans Affairs
- National Institutes of Health (2r01dk012829-36, 5p41rr002176-11)
- National Institute of Diabetes and Digestive and Kidney Diseases (DK 12829, DK-17047, R01DK029867, P30DK017047)
- National Center for Research Resources (RRO2176)
- Topics
- Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Cerebrospinal fluid and hydrocephalus
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
- Keywords
- insulin, cerebrospinal fluid, saturable transport, compartmental model, insulin clearance, dogs, food intake regulation
- MeSH terms
- Animals, Biological Transport, Brain, Dogs, Insulin, Kinetics, Male, Mathematics, Models, Biological, Time Factors
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