Intranasal insulin administration: A method for dissociating central and peripheral effects of insulin

Drugs of Today

Volumn 42, Issue 11, 2006, Pages 729-739

  Reger, Mark A ^a   Craft, Suzanne ^a,b  

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

^b GRECC   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

APOLIPOPROTEIN E; CEFALEXIN; GLUCOSE TRANSPORTER 2; GLUCOSE TRANSPORTER 4; HYDROCORTISONE; INSULIN; INSULIN RECEPTOR; INSULIN RECEPTOR SUBSTRATE 1; LEPTIN; N METHYL DEXTRO ASPARTIC ACID RECEPTOR; PLACEBO; SOMATOMEDIN C;

ALZHEIMER DISEASE; CARDIOVASCULAR DISEASE; CLINICAL TRIAL; COGNITION; CONTROLLED CLINICAL TRIAL; DOSE RESPONSE; DRUG ABSORPTION; DRUG EFFECT; DRUG MECHANISM; DRUG TRANSPORT; ENERGY CONSUMPTION; ENERGY METABOLISM; EVOKED BRAIN STEM AUDITORY RESPONSE; FOOD INTAKE; GENETIC RISK; GLUCOSE BLOOD LEVEL; GLUCOSE BRAIN LEVEL; GLUCOSE METABOLISM; GLUCOSE TRANSPORT; HUMAN; HYPERINSULINEMIA; HYPOGLYCEMIA; IMPAIRED GLUCOSE TOLERANCE; INSULIN BINDING; INSULIN BLOOD LEVEL; INSULIN RELEASE; INSULIN RESISTANCE; MEMORY; NON INSULIN DEPENDENT DIABETES MELLITUS; NONHUMAN; NOSE IRRITATION; OBESITY; PROTEIN EXPRESSION; RANDOMIZED CONTROLLED TRIAL; REVIEW; VERBAL MEMORY; WEIGHT REDUCTION;

ADMINISTRATION, INTRANASAL; ANIMALS; CENTRAL NERVOUS SYSTEM; DIABETES MELLITUS; GLUCOSE; HUMANS; HYPOGLYCEMIC AGENTS; INSULIN; NEURODEGENERATIVE DISEASES;

EID: 33846148284     PISSN: 16993993     EISSN: 16994019     Source Type: Journal    
DOI: 10.1358/dot.2006.42.11.1007675     Document Type: Review

References (99)

1. Gualandi-Signorini, A.M., Giorgi, G. Insulin formulations - A review. Eur Rev Med Pharmacol Sci 2001, 5: 73-83.
2. Banting, F., Best, C. The internal secretion of the pancreas. J Lab Clin Med 1922, 7: 256-71.
3. Joost, H.G., Thorens, B. The extended GLUT-family of sugar/polyol transport facilitators: Nomenclature, sequence characteristics, and potential function of its novel members (review). Mol Membr Biol 2001, 18: 247-56.
4. Davis, S., Granner, D. Insulin, oral hypoglycemic agents, and the pharmacology of the endocrine pancreas. In: Hardman, J., Limbird, L., Gilman, A. (Eds.). Goodman & Gilman's The Pharmacological Basis of Therapeutics. McGraw-Hill, New York 2001, 1679-1714.
5. Shii, K., Roth, R.A. Inhibition of insulin degradation by hepatoma cells after microinjection of monoclonal antibodies to a specific cytosolic protease. Proc Natl Acad Sci USA 1986, 83: 4147-51.
6. Ibberson, M., Uldry, M., Thorens, B. GLUTX1, a novel mammalian glucose transporter expressed in the central nervous system and insulin-sensitive tissues. Journal of Biological Chemistry 2000, 275: 4607-12.
7. Rea, S., James, D.E. Moving GLUT4: The biogenesis and trafficking of GLUT4 storage vesicles. Diabetes 1997, 46: 1667-77.
8. Mielke, J.G., Taghibiglou, C., Liu, L. et al. A biochemical and functional characterization of diet-induced brain insulin resistance. J Neurochem 2005, 93: 1568-78.
9. Banks, W.A., Jaspan, J.B., Kastin, A.J. Selective, physiological transport of insulin across the blood-brain barrier: Novel demonstration by species-specific radioimmunoassays. Peptides 1997, 18: 1257-62.
10. Baura, G.D., Foster, D.M., Porte, D. Jr. et al. 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 1993, 92: 1824-30.
11. Wallum, B.J., Taborsky, G.J., Porte, D. et al. Cerebrospinal fluid insulin levels increase during intravenous insulin infusions in man. J Clin Endocrinol Metab 1987, 64: 190-4.
12. Watson, G.S., Peskind, E.R., Asthana, S. et al. Insulin increases CSF Abeta42 levels in normal older adults. Neurology 2003, 60: 1899-903.
13. Stein, L.J., Dorsa, D.M., Baskin, D.G. et al. Reduced effect of experimental peripheral hyperinsulinemia to elevate cerebrospinal fluid insulin concentrations of obese Zucker rats. Endocrinology 1987, 121: 1611-5.
14. Kaiyala, K.J., Prigeon, R.L., Kahn, S.E., Woods, S.C., Schwartz, M.W. Obesity induced by a high-fat diet is associated with reduced brain insulin transport in dogs. Diabetes 2000, 49: 1525-33.
15. Schwartz, M.W., Figlewicz, D.F., Kahn, S.E. et al. Insulin binding to brain capillaries is reduced in genetically obese, hyperinsulinemic Zucker rats. Peptides, 1990, 11: 467-72.
16. Baskin, D.G., Stein, L.J., Ikeda, H. et al. Genetically obese Zucker rats have abnormally low brain insulin content. Life Sci 1985, 36: 627-33.
17. Israel, P.A., Park, C.R., Schwartz, M.W. et al. Effect of diet-induced obesity and experimental hyperinsulinemia on insulin uptake into CSF of the rat. Brain Res Bull 1993, 30: 571-5.
18. Abbott, M.A., Wells, D.G., Fallon, J.R. The insulin receptor tyrosine kinase substrate p58/53 and the insulin receptor are components of CNS synapses. J Neurosci 1999, 19: 7300-8.
19. Unger, J., Livingston, J., Moss, A. Insulin receptors in the central nervous system: Localization, signaling mechanisms and functional aspects. Prog Neurobiol 1991, 36: 343-62.
20. Havrankova, J., Roth, J. Insulin receptors are widely distributed in the central nervous system of the rat. Nature 1978, 272: 827-9.
21. Havrankova, J., Schmechel, D., Roth, J., Brownstein, M. Identification of insulin in rat brain. Proc Natl Acad Sci USA 1978, 75: 5737-41.
22. Baskin, D., Figlewicz, D., Woods, S., Porte, D., Dorsa, D. Insulin in the brain. Ann Rev Physiol 1987, 49: 335-47.
23. Baskin, D.G., Sipols, A.J., Schwartz, M.W., White, M.F. Immunocytochemical detection of insulin receptor substrate-1 (IRS-1) in rat brain: Colocalization with phosphotyrosine. Regul Pept 1993, 48: 257-66.
24. Corp, E.S., Woods, S.C., Porte, D. Jr. et al. Localization of 125I-insulin binding sites in the rat hypothalamus by quantitative autoradiography. Neurosci Lett 1986, 70: 17-22.
25. Zhao, W., Chen, H., Xu, H. et al. Brain insulin receptors and spatial memory. Correlated changes in gene expression, tyrosine phosphorylation, and signaling molecules in the hippocampus of water maze trained rats. J Biol Chem 1999, 274: 34893-902.
26. Baskin, D.G., Schwartz, M.W., Sipols, A.J. et al. Insulin receptor substrate-1 (IRS-1) expression in rat brain. Endocrinology 1994, 134: 1952-5.
27. Park, C.R., Seeley, R.J., Craft, S., Woods, S.C. Intracerebroventricular insulin enhances memory in a passive-avoidance task. Physiol Behav 2000, 68: 509-14.
28. Craft, S., Newcomer, J., Kanne, S. et al. Memory improvement following induced hyperinsulinemia in Alzheimer's disease. Neurobiol Aging 1996, 17: 123-30.
29. Craft, S., Asthana, S., Cook, D.G. et al. Insulin dose-response effects on memory and plasma amyloid precursor protein in Alzheimer's disease: Interactions with apolipoprotein E genotype. Psychoneuroendocrinology 2003, 28: 809-22.
30. Kern, W., Peters, A., Fruehwald-Schultes, E. et al. Improving influence of insulin on cognitive functions in humans. Neuroendocrinology 2001, 74: 270-80.
31. Craft, S., Asthana, S., Newcomer, J.W. et al. Enhancement of memory in Alzheimer disease with insulin and somatostatin, but not glucose. Arch Gen Psychiatry 1999, 56: 1135-40.
32. Watson, G.S., Craft, S. Modulation of memory by insulin and glucose: Neuropsychological observations in Alzheimer's disease. Eur J Pharmacol 2004, 490: 97-113.
33. Luchsinger, J.A., Tang, M.X., Shea, S., Mayeux, R. Hyperinsulinemia and risk of Alzheimer disease. Neurology 2004, 63: 1187-92.
34. Elias, P.K., Elias, M.F., D'Agostino, R.B. et al. NIDDM and blood pressure as risk factors for poor cognitive performance: The Framingham Study. Diabetes Care 1997, 20: 1388-95.
35. Helkala, E.L., Niskanen, L., Viinamaki, H., Partanen, J., Uusitupa, M. Short-term and long-term memory in elderly patients with NIDDM. Diabetes Care 1995, 18: 681-5.
36. Strachan, M.W., Deary, I.J., Ewing, F.M., Frier, B.M. Is type II diabetes associated with an increased risk of cognitive dysfunction? A critical review of published studies. Diabetes Care 1997, 20: 438-45.
37. Bingham, E.M., Hopkins, D., Smith, D. et al. The role of insulin in human brain glucose metabolism: An 18luoro-deoxyglucose positron emission tomography study. Diabetes 2002, 51: 3384-90.
38. Doyle, P., Cusin, I., Rohner-Jeanrenaud, F., Jeanrenaud, B. Four-day hyperinsulinemia in euglycemic conditions alters local cerebral glucose utilization in specific brain nuclei of freely moving rats. Brain Res 1995, 684: 47-55.
39. Lucignani, G., Namba, H., Nehlig, A. et al. Effects of insulin on local cerebral glucose utilization in the rat. J Cereb Blood Flow Metab 1987, 7: 309-14.
40. Marfaing, P., Penicaud, L., Broer, Y. et al. Effects of hyperinsulinemia on local cerebral insulin binding and glucose utilization in normoglycemic awake rats. Neurosci Lett 1990, 115: 279-85.
41. Apelt, J., Mehlhorn, G., Schliebs, R. Insulin-sensitive GLUT4 glucose transporters are colocalized with GLUT3-expressing cells and demonstrate a chemically distinct neuron-specific localization in rat brain. J Neurosci Res 1999, 57: 693-705.
42. Brant, A.M., Jess, T.J., Milligan, G., Brown, C.M., Gould, G.W. Immunological analysis of glucose transporters expressed in different regions of the rat brain and central nervous system. Biochem Biophys Res Commun 1993, 192: 1297-302.
43. El Messari, S., Leloup, C., Quignon, M. et al. Immunocytochemical localization of the insulin-responsive glucose transporter 4 (Glut4) in the rat central nervous system. J Comp Neurol 1998, 399: 492-512.
44. Livingstone, C., Lyall, H., Gould, G.W. Hypothalamic GLUT 4 expression: A glucose- and insulin-sensing mechanism? Mol Cell Endocrinol 1995, 107: 67-70.
45. Schulingkamp, R.J., Pagano, T.C., Hung, D., Raffa, R.B. Insulin receptors and insulin action in the brain: Review and clinical implications. Neurosci Biobehav Rev 2000, 24: 855-72.
46. Kopf, S.R., Baratti, C.M. Effects of posttraining administration of insulin on retention of a habituation response in mice: Participation of a central cholinergic mechanism. Neurobiol Learn Mem 1999, 71: 50-61.
47. Figlewicz, D.P., Szot, P., Israel, P.A., Payne, C., Dorsa, D.M. Insulin reduces norepinephrine transporter mRNA in vivo in rat locus coeruleus. Brain Res 1993, 602: 161-4.
48. Skeberdis, V.A., Lan, J., Zheng, X., Zukin, R.S., Bennett, M.V. Insulin promotes rapid delivery of N-methyl-D-aspartate receptors to the cell surface by exocytosis. Proc Natl Acad Sci USA 2001, 98: 3561-6.
49. Ahima, R.S., Osei, S.Y. Molecular regulation of eating behavior: New insights and prospects for therapeutic strategies. Trends Mol Med 2001, 7: 205-13.
50. Schwartz, M.W., Woods, S.C., Porte, D. Jr., Seeley, R.J., Baskin, D.G. Central nervous system control of food intake. Nature 2000, 404: 661-71.
51. Woods, S.C., Lotter, E.C., McKay, L.D., Porte, D. Jr. Chronic intracerebroventricular infusion of insulin reduces food intake and body weight of baboons. Nature 1979, 282: 503-5.
52. Air, E.L., Benoit, S.C., Blake Smith, K.A., Clegg, D.J., Woods, S.C. Acute third ventricular administration of insulin decreases food intake in two paradigms. Pharmacol Biochem Behav 2002, 72: 423-9.
53. Chavez, M., Kaiyala, K., Madden, L.J., Schwartz, M.W., Woods, S.C. Intraventricular insulin and the level of maintained body weight in rats. Behav Neurosci 1995, 109: 528-31.
54. Brief, D.J., Davis, J.D. Reduction of food intake and body weight by chronic intraventricular insulin infusion. Brain Res Bull 1984, 12: 571-5.
55. Figlewicz, D.P. Adiposity signals and food reward: Expanding the CNS roles of insulin and leptin. Am J Physiol Regul Integr Comp Physiol 2003, 284: R882-92.
56. Kern, W., Hallschmid, M., Born, J., Fehm, H. Reduced transport of insulin across the blood/brain barrier in obese humans. Diabetes 2003, 52 (Suppl. 1): A559.
57. Hallschmid, M., Benedict, C., Born, J., Fehm, H.L., Kern, W. Manipulating central nervous mechanisms of food intake and body weight regulation by intranasal administration of neuropeptides in man. Physiol Behav 2004, 83: 55-64.
58. Stockhorst, U., de Fries, D., Steingrueber, H.J., Scherbaum, W.A. Insulin and the CNS: Effects on food intake, memory, and endocrine parameters and the role of intranasal insulin administration in humans. Physiol Behav 2004, 83: 47-54.
59. Kern, W., Peters, A., Born, J., Fehm, H.L., Schultes, B. Changes in blood pressure and plasma catecholamine levels during prolonged hyperinsulinemia. Metabolism 2005, 54: 391-6.
60. Kern, W., Fittje, A., Fohr, W. et al. Increase in systolic blood pressure and catecholamine level during hyperinsulinemia in a placebocontrolled euglycemic clamp in healthy subjects. Exp Clin Endocrinol Diabetes 2000, 108: 498-505.
61. Mitrakou, A., Ryan, C., Veneman, T. et al. Hierarchy of glycemic thresholds for counter regulatory hormone secretion, symptoms, and cerebral dysfunction. Am J Physiol 1991, 260 (1 Pt. 1): E67-74.
62. Fruehwald-Schultes, B., Kern, W., Born, J., Fehm, H.L., Peters, A. Hyperinsulinemia causes activation of the hypothalamus-pituitary-adrenal axis in humans. Int J Obes Relat Metab Disord 2001, 25 (Suppl. 1): S38-40.
63. Ott, A., Stolk, R.P., van Harskamp, F. et al. Diabetes mellitus and the risk of dementia: The Rotterdam Study. Neurology 1999, 53: 1937-42.
64. Ho, L., Qin, W., Pompl, P.N. et al. Diet-induced insulin resistance promotes amyloidosis in a transgenic mouse model of Alzheimer's disease. Faseb J 2004, 18: 902-4.
65. Gerozissis, K., Orosco, M., Rouch, C., Nicolaidis, S. Basal and hyperinsulinemia-induced immunoreactive hypothalamic insulin changes in lean and genetically obese Zucker rats revealed by microdialysis. Brain Res 1993, 611: 258-63.
66. Schwartz, M.W., Figlewicz, D.F., Kahn, S.E. et al. Insulin binding to brain capillaries is reduced in genetically obese, hyperinsulinemic Zucker rats. Peptides 1990, 11: 467-72.
67. Craft, S., Peskind, E., Schwartz, M.W. et al. Cerebrospinal fluid and plasma insulin levels in Alzheimer's disease: Relationship to severity of dementia and apolipoprotein E genotype. Neurology 1998, 50: 164-8.
68. Craft, S., Asthana, S., Schellenberg, G. et al. Insulin effects on glucose metabolism, memory, and plasma amyloid precursor protein in Alzheimer's disease differ according to apolipoprotein-E genotype. Ann NY Acad Sci 2000, 903: 222-8.
69. Craft, S., Watson, G.S. Insulin and neurodegenerative disease: Shared and specific mechanisms. Lancet Neurol 2004, 3: 169-78.
70. Bodian, D., Howe, H.A. Experimental studies on intraneuronal spread of poliomyelitis virus. Bull Johns Hopkins Hosp 1941, 68: 248-67.
71. Faber, H.K. The early lesions of poliomyelitis after intranasal inoculation. J Pediat 1938, 13: 10-37.
72. Fairbrother, R.W., Hurst, E.W. The pathogenesis of, and propagation of the virus in, experimental poliomyeltis. J Path Bact 1930, 33: 17-45.
73. Czerniawska, A. Experimental investigations on the penetration of 198Au from nasal mucous membrane into cerebrospinal fluid. Acta Otolaryngol 1970, 70: 58-61.
74. Gopinath, P.G., Gopinath, G., Kumar, T.C.A. Target site of intranasally sprayed substances and their transport across the nasal mucosa: A new insight into the intranasal route of drug delivery. Curr Ther Res 1978, 23: 596-607.
75. Clark, W. E., Gros, L. Anatomical investigation into the routes by which infections may pass from the nasal cavities into the brain. In: Ministry of Health Report on Public Health and Medical Subjects. H.M. Stationary Office, London 1929.
76. Faber, W.M. The nasal mucosa and the subarachnoid space. Am J Anat 1937, 62: 121-48.
77. Weiss, P., Holland, Y. Neuronal dynamics and axonal flow, II. The olfactory nerve as a model test object. Proc Natl Acad Sci USA 1967, 57: 258-64.
78. Kristensson, K., Olsson, Y. Uptake of exogenous proteins in mouse olfactory cells. Acta Neuropathol (Berl) 1971, 19: 145-54.
79. Shipley, M.T. Transport of molecules from nose to brain: Transneuronal anterograde and retrograde labeling in the rat olfactory system by wheat germ agglutinin-horseradish peroxidase applied to the nasal epithelium. Brain Res Bull 1985, 15: 129-42.
80. Frey II, W.H. Intranasal delivery: Bypassing the blood-brain barrier to deliver therapeutic agents to the brain and spinal cord. Drug Deliv Technol 2002, 2: 46-9.
81. Thorne, R.G., Frey II, W.H. Delivery of neurotrophic factors to the central nervous system: Pharmacokinetic considerations. Clin Pharmacokinet 2001, 40: 907-46.
82. Thorne, R.G., Pronk, G.J., Padmanabhan, V., Frey II, W.H. Delivery of insulin-like growth factor-I to the rat brain and spinal cord along olfactory and trigeminal pathways following intranasal administration. Neuroscience 2004, 127: 481-96.
83. Balin, B.J., Broadwell, R.D., Salcman, M., el-Kalliny, M. Avenues for entry of peripherally administered protein to the central nervous system in mouse, rat, and squirrel monkey. J Comp Neurol 1986, 251: 260-80.
84. Broadwell, R.D., Balin, B.J. Endocytic and exocytic pathways of the neuronal secretory process and trans-synaptic transfer of wheat germ agglutinin-horseradish peroxidase in vivo. J Comp Neurol 1985, 242: 632-50.
85. Baker, H., Spencer, R.F. Transneuronal transport of peroxidase-conjugated wheat germ agglutinin (WGA-HRP) from the olfactory epithelium to the brain of the adult rat. Exp Brain Res 1986, 63: 461-73.
86. Thorne, R.G., Emory, C.R., Ala, T.A., Frey II, W.H. Quantitative analysis of the olfactory pathway for drug delivery to the brain. Brain Res 1995, 692: 278-82.
87. Pandini, G., Frasca, F., Mineo, R. et al. Insulin/i nsulin-like growth factor I hybrid receptors have different biological characteristics depending on the insulin receptor isoform involved. J Biol Chem 2002, 277: 39684-95.
88. Dupont, J., LeRoith, D. Insulin and insulin-like growth factor I receptors: Similarities and differences in signal transduction. Horm Res 2001, 55 (Suppl. 2): 22-6.
89. Sakane, T., Akizuki, M., Yoshida, M. et al. Transport of cephalexin to the cerebrospinal fluid directly from the nasal cavity. J Pharm Pharmacol 1991, 43: 449-51.
90. Van den Berg, M.P., Romeijn, S.G., Verhoef, J.C., Merkus, F.W. Serial cerebrospinal fluid sampling in a rat model to study drug uptake from the nasal cavity. J Neurosci Methods 2002, 116: 99-107.
91. Born, J., Lange, T., Kern, W. et al. Sniffing neuropeptides: A transnasal approach to the human brain. Nat Neurosci 2002, 5: 514-6.
92. Kern, W., Born, J., Schreiber, H., Fehm, H.L. Central nervous system effects of intranasally administered insulin during euglycemia in men. Diabetes 1999, 48: 557-63.
93. Reger, M.A., Watson, G.S., Frey II, W.H., et al. Effects of intranasal insulin on cognition in memory-impaired older adults: Modulation by APOE genotype. Neurobiol Aging 2006, 27: 451-88.
94. Hallschmid, M., Benedict, C., Schultes, B. et al. Intranasal insulin reduces body fat in men but not in women. Diabetes 2004, 53: 3024-9.
95. Benedict, C., Hallschmid, M., Hatke, A. et al. Intranasal insulin improves memory in humans. Psychoneuroendocrinology 2004, 29: 1326-34.
96. Kern, W., Peters, A., Fruhwald, B., Born, J., Fehm, H.L. Effects of hyperinsulinemia on sensory processing during an euglycemic clamp in healthy subjects. Exp Clin Endocrinol Diabetes 1998, 106: A15-16.
97. Baskin, D.G., Figlewicz Lattemann, D., Seeley, R.J. et al. Insulin and leptin: Dual adiposity signals to the brain for the regulation of food intake and body weight. Brain Res 1999, 848: 114-23.
98. Illum, L. Nasal drug delivery: New developments and strategies. Drug Discov Today 2002, 7: 1184-9.
99. Kupila, A., Sipila, J., Keskinen, P. et al. Intranasally administered insulin intended for prevention of type 1 diabetes - A safety study in healthy adults. Diabetes Metab Res Rev 2003, 19: 415-20.