Abstract
Eating behavior, body weight regulation, peripheral glucose metabolism, and cognitive function depend on adequate insulin action in the brain, and recent studies in humans suggested that impaired insulin action in the brain emerges upon fat intake, obesity, and genetic variants. As insulin enters into the brain in a receptor-mediated fashion, we hypothesized that whole-body insulin sensitivity might affect the transport of insulin into the brain and contribute to the aversive effect of insulin resistance in the central nervous system. In this study, we aimed to determine the ratio of insulin in the cerebrospinal fluid and serum to whole-body insulin sensitivity. Healthy human subjects participated in an oral glucose tolerance test to determine whole-body insulin sensitivity and underwent lumbar puncture. Blood and CSF concentrations of insulin were significantly correlated. The CSF/serum ratio for insulin was significantly associated with whole body insulin sensitivity with reduced insulin transported into the CSF in insulin-resistant subjects. Together, our data suggest that transport of insulin into the CSF relates to peripheral insulin sensitivity and impairs insulin action in the brain. This underlines the need for sensitizing measures in insulin-resistant subjects.
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Acknowledgments
We thank all study participants for their cooperation. The study was supported by a grant from the German Federal Ministry of Education and Research (BMBF) to the German Center for Diabetes Research (DZD e.V., 01GI0925).
Conflict of interest
Martin Heni, Patricia Schöpfer, Andreas Peter, Tina Sartorius, Andreas Fritsche, Matthis Synofzik, Hans-Ulrich Häring, Walter Maetzler, Anita M. Hennige declare they have no conflict of interest.
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Communicated by Massimo Porta.
Martin Heni, Andreas Peter, and Patricia Schöpfer have contributed equally to this work.
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Heni, M., Schöpfer, P., Peter, A. et al. Evidence for altered transport of insulin across the blood–brain barrier in insulin-resistant humans. Acta Diabetol 51, 679–681 (2014). https://doi.org/10.1007/s00592-013-0546-y
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DOI: https://doi.org/10.1007/s00592-013-0546-y