scholarly journals Triglycerides cross the blood–brain barrier and induce central leptin and insulin receptor resistance

2017 ◽  
Vol 42 (3) ◽  
pp. 391-397 ◽  
Author(s):  
W A Banks ◽  
S A Farr ◽  
T S Salameh ◽  
M L Niehoff ◽  
E M Rhea ◽  
...  
Keyword(s):  
Insulin Receptor ◽  
Blood Brain Barrier ◽  
Brain Barrier ◽  
Blood Brain

Diet and TNF-α differentially regulate the insulin receptor and its transporter at the blood–brain barrier

Appetite ◽  
2009 ◽  
Vol 52 (3) ◽  
pp. 817
Author(s):  
L. Asarian ◽  
S.M. Robinson ◽  
N. Geary ◽  
W. Langhans ◽  
W.A. Banks
Keyword(s):  
Insulin Receptor ◽  
Blood Brain Barrier ◽  
Brain Barrier ◽  
Blood Brain ◽  
Tnf Α

scholarly journals Mathematical Models of Blood-Brain Barrier Transport of Monoclonal Antibodies Targeting the Transferrin Receptor and the Insulin Receptor

2021 ◽  
Vol 14 (6) ◽  
pp. 535
Author(s):  
William M. Pardridge ◽  
Tom Chou
Keyword(s):  
Monoclonal Antibodies ◽  
Mathematical Models ◽  
Insulin Receptor ◽  
Blood Brain Barrier ◽  
Transferrin Receptor ◽  
Plasma Concentrations ◽  
Mass Action ◽  
Brain Barrier ◽  
Capillary Endothelium ◽  
Blood Brain

We develop and analyze mathematical models for receptor-mediated transcytosis of monoclonal antibodies (MAb) targeting the transferrin receptor (TfR) or the insulin receptor (IR), which are expressed at the blood-brain barrier (BBB). The mass-action kinetic model for both the TfR and IR antibodies were solved numerically to generate predictions for the concentrations of all species in all compartments considered. Using these models, we estimated the rates of MAb endocytosis into brain capillary endothelium, which forms the BBB in vivo, the rates of MAb exocytosis from the intra-endothelial compartment into brain extracellular space, and the rates of receptor recycling from the endothelial space back to the luminal endothelial plasma membrane. Our analysis highlights the optimal rates of MAb association with the targeted receptor. An important role of the endogenous ligand, transferrin (Tf) or insulin, in receptor-mediated-transport (RMT) of the associated MAb was found and was attributed to the five order magnitude difference between plasma concentrations of Tf (25,000 nM) and insulin (0.3 nM). Our modeling shows that the very high plasma concentration of Tf leads to only 5% of the endothelial TfR expressed on the luminal endothelial membrane.

scholarly journals The insulin receptor is expressed and functional in cultured blood-brain barrier endothelial cells but does not mediate insulin entry from blood to brain

2018 ◽  
Vol 315 (4) ◽  
pp. E531-E542 ◽  
Author(s):  
Maria Hersom ◽  
Hans C. Helms ◽  
Christoffer Schmalz ◽  
Thomas Å. Pedersen ◽  
Stephen T. Buckley ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Insulin Receptor ◽  
Blood Brain Barrier ◽  
Brain Barrier ◽  
Brain Endothelial Cells ◽  
Insulin Transport ◽  
Blood Brain ◽  
The Brain ◽  
Receptor Inhibitor

Insulin and its receptor are known to be present and functional in the brain. Insulin cerebrospinal fluid concentrations have been shown to correlate with plasma levels of insulin in a nonlinear fashion, indicative of a saturable transport pathway from the blood to the brain interstitial fluid. The aim of the present study was to investigate whether insulin was transported across brain endothelial cells in vitro via an insulin receptor-dependent pathway. The study showed that the insulin receptor was expressed at both the mRNA and protein levels in bovine brain endothelial cells. Luminally applied radiolabeled insulin showed insulin receptor-mediated binding to the endothelial cells. This caused a dose-dependent increase in Akt-phosphorylation, which was inhibited by coapplication of an insulin receptor inhibitor, s961, demonstrating activation of insulin receptor signaling pathways. Transport of insulin across the blood-brain barrier in vitro was low and comparable to that of a similarly sized paracellular marker. Furthermore, insulin transport was not inhibited by coapplication of an excess of unlabeled insulin or an insulin receptor inhibitor. The insulin transport and uptake studies were repeated in mouse brain endothelial cells demonstrating similar results. Although it cannot be ruled out that culture-induced changes in the cell model could have impaired a potential insulin transport mechanism, these in vitro data indicate that peripheral insulin must reach the brain parenchyma through alternative pathways rather than crossing the blood-brain barrier via receptor mediated transcytosis.

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