title: Intranasal Insulin Transport is Preserved in Aged SAMP8 Mice and is Altered by Albumin and Insulin Receptor Inhibition.
abstract: Insulin delivered to the level of the cribriform plate (intranasal insulin) is being investigated for its ability to enhance memory in people with Alzheimer's disease (AD). Recent work has shown intranasal insulin can be detected in young CD-1 mice within 5 min and is still present 60 min after injection. The current study determined whether intranasal insulin transport and the subsequent brain distribution of insulin varies in young, healthy mice (CD-1) compared to those with an AD-like phenotype (aged SAMP8) or those pre-disposed to develop such a phenotype (young SAMP8). We showed transport does not vary among these three mouse cohorts, suggesting that intranasal uptake and brain pharmacokinetics do not differ with AD-like signs or the genetic predisposition to developing them. We found that co-administration with bovine serum albumin increased levels of insulin in most brain regions. In addition, the insulin receptor inhibitor, S961, decreases the amount of insulin transported throughout the brain after intranasal injection. These results show insulin delivery to the brain by intranasal administration can be modified with agents such as albumin, may be dependent on the insulin receptor, and is not affected by an AD-like phenotype as presented by the SAMP8 mouse.
authors.affiliation: Department of Medicine, Division of Gerontology and Geriatric Medicine, University of Washington School of Medicine, Seattle, WA, USA.
authors.forename: Elizabeth M
authors.initials: EM
authors.lastname: Rhea
authors.affiliation: University of Colorado School of Medicine, Aurora, CO, USA.
authors.forename: Samantha R
authors.initials: SR
authors.lastname: Humann
authors.affiliation: University of Washington School of Medicine, Seattle, WA, USA.
authors.forename: Surabhi
authors.initials: S
authors.lastname: Nirkhe
authors.affiliation: Department of Internal Medicine, Division of Geriatrics, Saint Louis University, St. Louis, MO, USA.|Research and Development Service, VA Medical Center, St. Louis, MO, USA.
authors.forename: Susan A
authors.initials: SA
authors.lastname: Farr
authors.affiliation: Department of Internal Medicine, Division of Geriatrics, Saint Louis University, St. Louis, MO, USA.
authors.forename: John E
authors.initials: JE
authors.lastname: Morley
authors.affiliation: Department of Medicine, Division of Gerontology and Geriatric Medicine, University of Washington School of Medicine, Seattle, WA, USA.
authors.forename: William A
authors.initials: WA
authors.lastname: Banks
mesh_terms: D000281:Administration, Intranasal; D000375:Aging / Q000378:metabolism*; D000418:Albumins / Q000494:pharmacology; D000544:Alzheimer Disease / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002491:Central Nervous System Agents / Q000494:pharmacology; D015331:Cohort Studies; D004195:Disease Models, Animal; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D007328:Insulin / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D007457:Iodine Radioisotopes; D008297:Male; D010455:Peptides / Q000494:pharmacology; D011972:Receptor, Insulin / Q000037:antagonists & inhibitors / Q000378:metabolism; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000493:pharmacokinetics
chemical_list: D000418:Albumins; D002491:Central Nervous System Agents; D007004:Hypoglycemic Agents; D007328:Insulin; D007457:Iodine Radioisotopes; D010455:Peptides; D011994:Recombinant Proteins; C532752:S961 peptide; D011972:Receptor, Insulin
keywords: Alzheimer’s disease; insulin; intranasal administration; pharmacokinetics