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 [6,6-2H2]glucose, hepatocellular lipids (HCLs), ATP, and inorganic phosphate concentrations with 1H/31P 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.
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Nasal insulin did not modulate endogenous glucose production under systemic fasting insulin concentrations in most clinical trials.
“as nasal insulin did not modulate endogenous glucose production under systemic fasting insulin concentrations in most12,14, but not all, clinical trials11.”
From Brain insulin action on peripheral insulin sensitivity in women depends on menstrual cycle phase (2023) · cites this paper as [14]
IN insulin improves hepatic energy metabolism in healthy humans but not in patients with type 2 diabetes.
“These outcomes expand findings that IN insulin improves hepatic energy metabolism in healthy humans but not in patients with type 2 diabetes”
From Intranasal insulin (2021) · cites this paper as [82]
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- Authors
- Gancheva, S., Koliaki, C., Bierwagen, A., Nowotny, P., Heni, M., Fritsche, A., Häring, H.-U., Szendroedi, J., & Roden, M.
- Affiliations
- Deutsches Diabetes-Zentrum e.V. (DE)
- German Center for Diabetes Research (DE)
- Düsseldorf University Hospital (DE)
- Corresponding author
- Roden, Michael
- ORCID
- Venue
- Diabetes
- Publisher
- American Diabetes Association
- Published
- 2015-01-09
- Volume
- 64
- Issue
- 6
- Pages
- 1966-1975
- ISSN
- 0012-1797 (ISSN-L)
- 1939-327X
- OpenAlex
- W2155621221
- Cited by
- 81
- References
- 47
- Citations by year
- 2026: 4 · 2025: 2 · 2024: 6 · 2023: 3 · 2022: 4 · 2021: 10 · 2020: 8 · 2019: 4 · 2018: 9 · 2017: 13 · 2016: 10 · 2015: 8
- FWCI
- 13.42
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Diabetes (publishedVersion)
- PubMed (publishedVersion)
- Site cant be reached (submittedVersion)
- PuSH - Publication Server of Helmholtz Zentrum München (submittedVersion)
- Funders
- Helmholtz Alliance Imaging and Curing Environmental Metabolic Diseases
- Ministry of Science and Research of the State of North Rhine-Westphalia
- German Federal Ministry of Health
- German Center for Diabetes Research
- Schmutzler Stiftung
- Topics
- Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Health Sciences › Medicine › Epidemiology › Liver Disease Diagnosis and Treatment
- Keywords
- intranasal insulin, hepatic insulin sensitivity, hepatic lipid accumulation, hepatic energy metabolism, type 2 diabetes, endogenous glucose production, hepatic ATP, inorganic phosphate, intravenous insulin, insulin resistance
- MeSH terms
- Administration, Intranasal, Energy Metabolism, Female, Humans, Insulin, Liver, Male, Gas Chromatography-Mass Spectrometry, Middle Aged, Magnetic Resonance Spectroscopy, Lipid Metabolism
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