title: Insulin delivery to the brain using intracranial implantation of alginate-encapsulated pancreatic islets.
abstract: There is increasing evidence supporting a link between cognitive dysfunctions and impaired brain insulin signalling. Insulin therapy has previously been tested as an approach to ameliorate brain insulin resistance and deficiency in patients with various brain disorders. However, current strategies for insulin delivery to the brain may induce severe hypoglycaemia when injected peripherally or show poor uptake when delivered intranasally. Recently, we have shown that intracranial transplantation of naked pancreatic islets increased insulin content in the brain and attenuated cognitive dysfunctions without altering peripheral glucose homeostasis in rats with schizophrenia-like syndrome. In this study, we show that intracranial implantation of 50 pancreatic islets encapsulated in disc-shaped alginate is sufficient to elevate insulin content in the rat brain. Three weeks after implantation, the islets displayed intact morphology, intensive hormone staining and glucose-sensitive insulin release. The ultrapure alginate with high guluronic acid content used for islet encapsulation demonstrated good biocompatibility and stability after intracranial implantation. All implanted animals were normoglycaemic and normoinsulinaemic. In conclusion, the intracranial implantation of a small amount of alginate-encapsulated islets is an efficient tool for metabolically regulated insulin delivery to the brain. Copyright © 2017 John Wiley & Sons, Ltd.
authors.affiliation: Laboratory of Diabetes and Obesity Research, Felsenstein Medical Research Center, Sackler Faculty of Medicine, Tel Aviv University, Beilinson Campus, Petah Tikva, Israel.
authors.forename: Konstantin
authors.initials: K
authors.lastname: Bloch
authors.affiliation: Laboratory of Transplantation, Felsenstein Medical Research Center, Sackler Faculty of Medicine, Tel Aviv University, Beilinson Campus, Petah Tikva, Israel.
authors.forename: Alexey
authors.initials: A
authors.lastname: Vanichkin
authors.affiliation: Laboratory of Biological Psychiatry, Felsenstein Medical Research Center, Sackler Faculty of Medicine, Tel Aviv University, Beilinson Campus, Petah Tikva, Israel.
authors.forename: Irit
authors.initials: I
authors.lastname: Gil-Ad
authors.affiliation: Laboratory of Diabetes and Obesity Research, Felsenstein Medical Research Center, Sackler Faculty of Medicine, Tel Aviv University, Beilinson Campus, Petah Tikva, Israel.
authors.forename: Pnina
authors.initials: P
authors.lastname: Vardi
authors.affiliation: Laboratory of Biological Psychiatry, Felsenstein Medical Research Center, Sackler Faculty of Medicine, Tel Aviv University, Beilinson Campus, Petah Tikva, Israel.|Research Unit, Geha Mental Health Center, Petah Tikva, Israel.
authors.forename: Abraham
authors.initials: A
authors.lastname: Weizman
mesh_terms: D000464:Alginates / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D001921:Brain / Q000378:metabolism*; D018914:Cells, Immobilized / Q000378:metabolism / Q000637:transplantation; D020723:Glucuronic Acid / Q000737:chemistry / Q000494:pharmacology; D006603:Hexuronic Acids / Q000737:chemistry / Q000494:pharmacology; D007003:Hypoglycemia / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D007328:Insulin / Q000378:metabolism*; D007515:Islets of Langerhans / Q000378:metabolism*; D016381:Islets of Langerhans Transplantation; D008297:Male; D051381:Rats; D014185:Transplantation, Isogeneic
chemical_list: D000464:Alginates; D006603:Hexuronic Acids; D007328:Insulin; D020723:Glucuronic Acid
keywords: alginate; brain insulin; encapsulation; immunoisolation; pancreatic islet implantation; peripheral glucose homeostasis