Insulin transport across the blood–brain barrier can occur independently of the insulin receptor

Journal of Physiology

Volumn 596, Issue 19, 2018, Pages 4753-4765

  Rhea, Elizabeth M ^a,b   Rask Madsen, Christian ^c   Banks, William A ^a,b  

^a Research and Development   (United States)

^b UNIVERSITY OF WASHINGTON SCHOOL OF MEDICINE   (United States)

^c HARVARD MEDICAL SCHOOL   (United States)

Author keywords

blood brain barrier; insulin receptor; insulin transport

Indexed keywords

INSULIN; INSULIN RECEPTOR; PEPTIDE; S961 PEPTIDE;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL TISSUE; ARTICLE; BLOOD BRAIN BARRIER; BRAIN CELL; CELL LOSS; CONTROLLED STUDY; ENDOTHELIUM CELL; HORMONE ACTION; HORMONE TRANSPORT; IMMUNOREACTIVITY; IN VIVO STUDY; INSULIN BINDING; MALE; MOUSE; NONHUMAN; PRIORITY JOURNAL; PROTEIN FUNCTION; PROTEIN STABILITY; RECEPTOR BINDING; SIGNAL TRANSDUCTION; ANIMAL; BRAIN; CELL MEMBRANE PERMEABILITY; CYTOLOGY; DRUG EFFECT; KNOCKOUT MOUSE; METABOLISM; PHYSIOLOGY; TRANSPORT AT THE CELLULAR LEVEL;

ANIMALS; BIOLOGICAL TRANSPORT; BLOOD-BRAIN BARRIER; BRAIN; CELL MEMBRANE PERMEABILITY; ENDOTHELIAL CELLS; INSULIN; MALE; MICE; MICE, KNOCKOUT; PEPTIDES; RECEPTOR, INSULIN;

EID: 85052789026     PISSN: 00223751     EISSN: 14697793     Source Type: Journal    
DOI: 10.1113/JP276149     Document Type: Article

References (59)

1. Banks WA (2004). The source of cerebral insulin. Eur J Pharmacol 490, 5–12.
2. Banks WA, Jaspan JB, Huang W & Kastin AJ (1997a). Transport of insulin across the blood-brain barrier: saturability at euglycemic doses of insulin. Peptides 18, 1423–1429.
3. Banks WA, Jaspan JB & Kastin AJ (1997b). Effect of diabetes mellitus on the permeability of the blood-brain barrier to insulin. Peptides 18, 1577–1584.
4. Banks WA, Jaspan JB & Kastin AJ (1997c). Selective, physiological transport of insulin across the blood-brain barrier: novel demonstration by species-specific radioimmunoassays. Peptides 18, 1257–1262.
5. Banks WA & Kastin AJ (1998). Differential permeability of the blood-brain barrier to two pancreatic peptides: insulin and amylin. Peptides 19, 883–889.
6. Banks WA, Kastin AJ, Huang W, Jaspan JB & Maness LM (1996). Leptin enters the brain by a saturable system independent of insulin. Peptides 17, 305–311.
7. Banks WA, Kastin AJ & Pan W (1999). Uptake and degradation of blood-borne insulin by the olfactory bulb. Peptides 20, 373–378.
8. Banks WA, Owen JB & Erickson MA (2012). Insulin in the brain: there and back again. Pharmacol Ther 136, 82–93.
9. Bar RS, DeRose A, Sandra A, Peacock ML & Owen WG (1983). Insulin binding to microvascular endothelium of intact heart: a kinetic and morphometric analysis. Am J Physiol 244, E447–E452.
10. Baura GD, Foster DM, Porte D Jr, Kahn SE, Bergman RN, Cobelli C & Schwartz MW (1993). Saturable transport of insulin from plasma into the central nervous system of dogs in vivo. A mechanism for regulated insulin delivery to the brain. J Clin Invest 92, 1824–1830.
11. Benedict C, Hallschmid M, Hatke A, Schultes B, Fehm HL, Born J & Kern W (2004). Intranasal insulin improves memory in humans. Psychoneuroendocrinology 29, 1326–1334.
12. Blasberg RG, Fenstermacher JD & Patlak CS (1983). Transport of α-aminoisobutyric acid across brain capillary and cellular membranes. J Cereb Blood Flow Metab 3, 8–32.
13. Cashion MF, Banks WA & Kastin AJ (1996). Sequestration of centrally administered insulin by the brain: effects of starvation, aluminum, and TNF-α. Horm Behav 30, 280–286.
14. Chan JY, LaPara K & Yee D (2016). Disruption of insulin receptor function inhibits proliferation in endocrine-resistant breast cancer cells. Oncogene 35, 4235–4243.
15. Claxton A, Baker LD, Hanson A, Trittschuh EH, Cholerton B, Morgan A, Callaghan M, Arbuckle M, Behl C & Craft S (2015). Long acting intranasal insulin detemir improves cognition for adults with mild cognitive impairment or early-stage Alzheimer's disease dementia. J Alzheimers Dis 45, 1269–1270.
16. Craft S, Newcomer J, Kanne S, Dagogo-Jack S, Cryer P, Sheline Y, Luby J, Dagogo-Jack A & Alderson A (1996). Memory improvement following induced hyperinsulinemia in Alzheimer's disease. Neurobiol Aging 17, 123–130.
17. Craft S, Peskind E, Schwartz MW, Schellenberg GD, Raskind M & Porte D Jr (1998). Cerebrospinal fluid and plasma insulin levels in Alzheimer's disease: relationship to severity of dementia and apolipoprotein E genotype. Neurology 50, 164–168.
18. Cserr HF & Berman BJ (1978). Iodide and thiocyanate efflux from brain following injection into rat caudate nucleus. Am J Physiol 235, F331–F337.
19. Dogrukol-Ak D, Kumar VB, Ryerse JS, Farr SA, Verma S, Nonaka N, Nakamachi T, Ohtaki H, Niehoff ML, Edwards JC, Shioda S, Morley JE & Banks WA (2009). Isolation of peptide transport system-6 from brain endothelial cells: therapeutic effects with antisense inhibition in Alzheimer and stroke models. J Cereb Blood Flow Metab 29, 411–422.
20. Duffy KR & Pardridge WM (1987). Blood-brain-barrier transcytosis of insulin in developing rabbits. Brain Res 420, 32–38.
21. 131. J Clin Invest 33, 1252–1260.
22. Frank HJ, Jankovic-Vokes T, Pardridge WM & Morris WL (1985). Enhanced insulin binding to blood-brain barrier in vivo and to brain microvessels in vitro in newborn rabbits. Diabetes 34, 728–733.
23. Frank HJ, Pardridge WM, Morris WL, Rosenfeld RG & Choi TB (1986). Binding and internalization of insulin and insulin-like growth factors by isolated brain microvessels. Diabetes 35, 654–661.
24. Frolich L, Blum-Degen D, Bernstein HG, Engelsberger S, Humrich J, Laufer S, Muschner D, Thalheimer A, Turk A, Hoyer S, Zochling R, Boissl KW, Jellinger K & Riederer P (1998). Brain insulin and insulin receptors in aging and sporadic Alzheimer's disease. J Neural Transm (Vienna) 105, 423–438.
25. 3H]dopa in various regions of the brain. J Neurochem 13, 655–669.
26. Gray SM, Aylor KW & Barrett EJ (2017). Unravelling the regulation of insulin transport across the brain endothelial cell. Diabetologia 60, 1512–1521.
27. Haugaard N, Vaughan M, Haugaard ES & Stadie WC (1954). Studies of radioactive injected labeled insulin. J Biol Chem 208, 549–563.
28. Hersom M, Helms HC, Schmalz C, Pedersen TA, Buckley ST & Brodin B (2018). The insulin receptor is expressed and functional in cultured blood-brain barrier endothelial cells, but does not mediate insulin entry from blood-to-brain. Am J Physiol Endocrinol Metab (in press; http://doi.org/10.1152/ajpendo.00350.2016).
29. Jialal I, Crettaz M, Hachiya HL, Kahn CR, Moses AC, Buzney SM & King GL (1985). Characterization of the receptors for insulin and the insulin-like growth factors on micro- and macrovascular tissues. Endocrinology 117, 1222–1229.
30. Kastin AJ & Pan W (2008). Blood-brain barrier and feeding: regulatory roles of saturable transport systems for ingestive peptides. Curr Pharm Des 14, 1615–1619.
31. King GL & Johnson SM (1985). Receptor-mediated transport of insulin across endothelial cells. Science 227, 1583–1586.
32. Konishi M, Sakaguchi M, Lockhart SM, Cai W, Li ME, Homan EP, Rask-Madsen C & Kahn CR (2017). Endothelial insulin receptors differentially control insulin signalling kinetics in peripheral tissues and brain of mice. Proc Natl Acad Sci U S A 114, E8478–E8487.
33. Meijer RI, Gray SM, Aylor KW & Barrett EJ (2016). Pathways for insulin access to the brain: the role of the microvascular endothelial cell. Am J Physiol Heart Circ Physiol 311, H1132–H1138.
34. Miller DW, Keller BT & Borchardt RT (1994). Identification and distribution of insulin receptors on cultured bovine brain microvessel endothelial cells: possible function in insulin processing in the blood-brain barrier. J Cell Physiol 161, 333–341.
35. Nelson TJ, Sun MK, Hongpaisan J & Alkon DL (2008). Insulin, PKC signalling pathways and synaptic remodelling during memory storage and neuronal repair. Eur J Pharmacol 585, 76–87.
36. Novak V, Milberg W, Hao Y, Munshi M, Novak P, Galica A, Manor B, Roberson P, Craft S & Abduljalil A (2014). Enhancement of vasoreactivity and cognition by intranasal insulin in type 2 diabetes. Diabetes Care 37, 751–759.
37. Orlando RA, Rader K, Authier F, Yamazaki H, Posner BI, Bergeron JJ & Farquhar MG (1998). Megalin is an endocytic receptor for insulin. J Am Soc Nephrol 9, 1759–1766.
38. Pan W & Kastin AJ (1999). Entry of EGF into brain is rapid and saturable. Peptides 20, 1091–1098.
39. Pan W & Kastin AJ (2002). TNFα transport across the blood-brain barrier is abolished in receptor knockout mice. Exp Neurol 174, 193–200.
40. Pardridge WM, Eisenberg J & Yang J (1985). Human blood-brain barrier insulin receptor. J Neurochem 44, 1771–1778.
41. Patlak CS, Blasberg RG & Fenstermacher JD (1983). Graphical evaluation of blood-to-brain transfer constants from multiple-time uptake data. J Cereb Blood Flow Metab 3, 1–7.
42. Porte D Jr, Baskin DG & Schwartz MW (2005). Insulin signalling in the central nervous system: a critical role in metabolic homeostasis and disease from C. elegans to humans. Diabetes 54, 1264–1276.
43. Procaccini C, Santopaolo M, Faicchia D, Colamatteo A, Formisano L, de Candia P, Galgani M, De Rosa V & Matarese G (2016). Role of metabolism in neurodegenerative disorders. Metabolism 65, 1376–1390.
44. Reger MA, Watson GS, Green PS, Wilkinson CW, Baker LD, Cholerton B, Fishel MA, Plymate SR, Breitner JC, DeGroodt W, Mehta P & Craft S (2008). Intranasal insulin improves cognition and modulates β-amyloid in early AD. Neurology 70, 440–448.
45. Salameh TS, Bullock KM, Hujoel IA, Niehoff ML, Wolden-Hanson T, Kim J, Morley JE, Farr SA & Banks WA (2015). Central nervous system delivery of intranasal insulin: mechanisms of uptake and effects on cognition. J Alzheimers Dis 47, 715–728.
46. Schaffer L, Brand CL, Hansen BF, Ribel U, Shaw AC, Slaaby R & Sturis J (2008). A novel high-affinity peptide antagonist to the insulin receptor. Biochem Biophys Res Commun 376, 380–383.
47. Schwartz MW, Bergman RN, Kahn SE, Taborsky GJ Jr, Fisher LD, Sipols AJ, Woods SC, Steil GM & Porte D Jr (1991). Evidence for entry of plasma insulin into cerebrospinal fluid through an intermediate compartment in dogs. Quantitative aspects and implications for transport. J Clin Invest 88, 1272–1281.
48. Schwartz MW, Figlewicz DF, Kahn SE, Baskin DG, Greenwood MR & Porte D Jr (1990). Insulin binding to brain capillaries is reduced in genetically obese, hyperinsulinemic Zucker rats. Peptides 11, 467–472.
49. Schwartz MW, Figlewicz DP, Baskin DG, Woods SC & Porte D Jr (1992). Insulin in the brain: a hormonal regulator of energy balance. Endocr Rev 13, 387–414.
50. Triguero D, Buciak J & Pardridge WM (1990). Capillary depletion method for quantification of blood-brain barrier transport of circulating peptides and plasma proteins. J Neurochem 54, 1882–1888.
51. Urayama A & Banks WA (2008). Starvation and triglycerides reverse the obesity-induced impairment of insulin transport at the blood-brain barrier. Endocrinology 149, 3592–3597.
52. van Houten M & Posner BI (1979). Insulin binds to brain blood vessels in vivo. Nature 282, 623–625.
53. Vicent D, Ilany J, Kondo T, Naruse K, Fisher SJ, Kisanuki YY, Bursell S, Yanagisawa M, King GL & Kahn CR (2003). The role of endothelial insulin signalling in the regulation of vascular tone and insulin resistance. J Clin Invest 111, 1373–1380.
54. Vikram A & Jena G (2010). S961, an insulin receptor antagonist causes hyperinsulinemia, insulin-resistance and depletion of energy stores in rats. Biochem Biophys Res Commun 398, 260–265.
55. Wang X, Haring MF, Rathjen T, Lockhart SM, Sorensen D, Ussar S, Rasmussen LM, Bertagnolli MM, Kahn CR & Rask-Madsen C (2017). Insulin resistance in vascular endothelial cells promotes intestinal tumour formation. Oncogene 36, 4987–4996.
56. Wilcox G (2005). Insulin and insulin resistance. Clin Biochem Rev 26, 19–39.
57. Williams IM, Valenzuela FA, Kahl SD, Ramkrishna D, Mezo AR, Young JD, Wells KS & Wasserman DH (2018). Insulin exits skeletal muscle capillaries by fluid-phase transport. J Clin Invest 128, 699–714.
58. Yu Y, Kastin AJ & Pan W (2006). Reciprocal interactions of insulin and insulin-like growth factor I in receptor-mediated transport across the blood-brain barrier. Endocrinology 147, 2611–2615.
59. Zar JH (1984). Biostatistical Analysis. Prentice-Hall, Englewood Cliffs, NJ, USA.