title: Effects of intranasal insulin on hepatic fat accumulation and energy metabolism in humans.
abstract: Studies in rodents suggest that insulin controls hepatic glucose metabolism through brain-liver crosstalk, but human studies using intranasal insulin to mimic central insulin delivery have provided conflicting results. In this randomized controlled crossover trial, we investigated the effects of intranasal insulin on hepatic insulin sensitivity (HIS) and energy metabolism in 10 patients with type 2 diabetes and 10 lean healthy participants (CON). Endogenous glucose production was monitored with [6,6-(2)H2]glucose, hepatocellular lipids (HCLs), ATP, and inorganic phosphate concentrations with (1)H/(31)P magnetic resonance spectroscopy. Intranasal insulin transiently increased serum insulin levels followed by a gradual lowering of blood glucose in CON only. Fasting HIS index was not affected by intranasal insulin in CON and patients. HCLs decreased by 35% in CON only, whereas absolute hepatic ATP concentration increased by 18% after 3 h. A subgroup of CON received intravenous insulin to mimic the changes in serum insulin and blood glucose levels observed after intranasal insulin. This resulted in a 34% increase in HCLs without altering hepatic ATP concentrations. In conclusion, intranasal insulin does not affect HIS but rapidly improves hepatic energy metabolism in healthy humans, which is independent of peripheral insulinemia. These effects are blunted in patients with type 2 diabetes.
authors.affiliation: Institute for Clinical Diabetology, German Diabetes Center, Leibniz Institute for Diabetes Research, Heinrich Heine University Düsseldorf, Düsseldorf, Germany German Center for Diabetes Research (DZD e.V.), Partner Düsseldorf, Düsseldorf, Germany.
authors.forename: Sofiya
authors.initials: S
authors.lastname: Gancheva
authors.affiliation: Institute for Clinical Diabetology, German Diabetes Center, Leibniz Institute for Diabetes Research, Heinrich Heine University Düsseldorf, Düsseldorf, Germany German Center for Diabetes Research (DZD e.V.), Partner Düsseldorf, Düsseldorf, Germany.
authors.forename: Chrysi
authors.initials: C
authors.lastname: Koliaki
authors.affiliation: Institute for Clinical Diabetology, German Diabetes Center, Leibniz Institute for Diabetes Research, Heinrich Heine University Düsseldorf, Düsseldorf, Germany German Center for Diabetes Research (DZD e.V.), Partner Düsseldorf, Düsseldorf, Germany.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Bierwagen
authors.affiliation: Institute for Clinical Diabetology, German Diabetes Center, Leibniz Institute for Diabetes Research, Heinrich Heine University Düsseldorf, Düsseldorf, Germany German Center for Diabetes Research (DZD e.V.), Partner Düsseldorf, Düsseldorf, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Nowotny
authors.affiliation: Department of Internal Medicine, Division of Endocrinology, Diabetology, Angiology, Nephrology and Clinical Chemistry, Eberhard Karls University, Tübingen, Germany Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich at the University of Tübingen (Paul Langerhans Institute Tübingen), Tübingen, Germany German Center for Diabetes Research (DZD e.V.), Partner Neuherberg, Neuherberg, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Heni
authors.affiliation: Department of Internal Medicine, Division of Endocrinology, Diabetology, Angiology, Nephrology and Clinical Chemistry, Eberhard Karls University, Tübingen, Germany Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich at the University of Tübingen (Paul Langerhans Institute Tübingen), Tübingen, Germany German Center for Diabetes Research (DZD e.V.), Partner Neuherberg, Neuherberg, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Fritsche
authors.affiliation: Department of Internal Medicine, Division of Endocrinology, Diabetology, Angiology, Nephrology and Clinical Chemistry, Eberhard Karls University, Tübingen, Germany Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich at the University of Tübingen (Paul Langerhans Institute Tübingen), Tübingen, Germany German Center for Diabetes Research (DZD e.V.), Partner Neuherberg, Neuherberg, Germany.
authors.forename: Hans-Ulrich
authors.initials: HU
authors.lastname: Häring
authors.affiliation: Institute for Clinical Diabetology, German Diabetes Center, Leibniz Institute for Diabetes Research, Heinrich Heine University Düsseldorf, Düsseldorf, Germany German Center for Diabetes Research (DZD e.V.), Partner Düsseldorf, Düsseldorf, Germany Department of Endocrinology and Diabetology, University Hospital, Düsseldorf, Germany.
authors.forename: Julia
authors.initials: J
authors.lastname: Szendroedi
authors.affiliation: Institute for Clinical Diabetology, German Diabetes Center, Leibniz Institute for Diabetes Research, Heinrich Heine University Düsseldorf, Düsseldorf, Germany German Center for Diabetes Research (DZD e.V.), Partner Düsseldorf, Düsseldorf, Germany Department of Endocrinology and Diabetology, University Hospital, Düsseldorf, Germany michael.roden@ddz.uni-duesseldorf.de.
authors.forename: Michael
authors.initials: M
authors.lastname: Roden
mesh_terms: D000281:Administration, Intranasal; D004734:Energy Metabolism / Q000187:drug effects*; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D007328:Insulin / Q000008:administration & dosage / Q000494:pharmacology*; D050356:Lipid Metabolism / Q000187:drug effects*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008875:Middle Aged
chemical_list: D007328:Insulin