title: Intranasal insulin suppresses endogenous glucose production in humans compared with placebo in the presence of similar venous insulin concentrations.
abstract: Intranasal insulin (INI) has been shown to modulate food intake and food-related activity in the central nervous system in humans. Because INI increases insulin concentration in the cerebrospinal fluid, these effects have been postulated to be mediated via insulin action in the brain, although peripheral effects of insulin cannot be excluded. INI has been shown to lower plasma glucose in some studies, but whether it regulates endogenous glucose production (EGP) is not known. To assess the role of INI in the regulation of EGP, eight healthy men were studied in a single-blind, crossover study with two randomized visits (one with 40 IU INI and the other with intranasal placebo [INP] administration) 4 weeks apart. EGP was assessed under conditions of an arterial pancreatic clamp, with a primed, constant infusion of deuterated glucose and infusion of 20% dextrose as required to maintain euglycemia. Between 180 and 360 min after administration, INI significantly suppressed EGP by 35.6% compared with INP, despite similar venous insulin concentrations. In conclusion, INI lowers EGP in humans compared with INP, despite similar venous insulin concentrations. INI may therefore be of value in treating excess liver glucose production in diabetes.
authors.affiliation: Departments of Medicine and Physiology and the Banting and Best Diabetes Centre, University of Toronto, Toronto, Ontario, Canada, and Division of Endocrinology, Department of Medicine, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Satya
authors.initials: S
authors.lastname: Dash
authors.affiliation: Departments of Medicine and Physiology and the Banting and Best Diabetes Centre, University of Toronto, Toronto, Ontario, Canada, and Division of Endocrinology, Department of Medicine, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Changting
authors.initials: C
authors.lastname: Xiao
authors.affiliation: Departments of Medicine and Physiology and the Banting and Best Diabetes Centre, University of Toronto, Toronto, Ontario, Canada, and Division of Endocrinology, Department of Medicine, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Morgantini
authors.affiliation: Departments of Medicine and Physiology and the Banting and Best Diabetes Centre, University of Toronto, Toronto, Ontario, Canada, and Division of Endocrinology, Department of Medicine, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Khajag
authors.initials: K
authors.lastname: Koulajian
authors.affiliation: Departments of Medicine and Physiology and the Banting and Best Diabetes Centre, University of Toronto, Toronto, Ontario, Canada, and Division of Endocrinology, Department of Medicine, University of Toronto, Toronto, Ontario, Canada gary.lewis@uhn.ca.
authors.forename: Gary F
authors.initials: GF
authors.lastname: Lewis
mesh_terms: D000281:Administration, Intranasal; D001786:Blood Glucose / Q000187:drug effects; D018592:Cross-Over Studies; D005947:Glucose / Q000378:metabolism*; D064368:Healthy Volunteers; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000494:pharmacology*; D007328:Insulin / Q000008:administration & dosage* / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D016037:Single-Blind Method
chemical_list: D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D005947:Glucose