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.
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In healthy men, insulin action in the brain suppresses endogenous glucose production.
“Studies performed in healthy men found that insulin action in the brain suppresses endogenous glucose production3,11”
From Brain insulin action on peripheral insulin sensitivity in women depends on menstrual cycle phase (2023) · cites this paper as [11]
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 [11]
The current study corroborates that insulin action in the human brain modulates peripheral insulin sensitivity.
“The current study corroborates that insulin action in the human brain modulates peripheral insulin sensitivity3,4,11”
From Brain insulin action on peripheral insulin sensitivity in women depends on menstrual cycle phase (2023) · cites this paper as [11]
Insulin action in the human brain modulates peripheral insulin sensitivity.
“The current study corroborates that insulin action in the human brain modulates peripheral insulin sensitivity3,4,11”
From Brain insulin action on peripheral insulin sensitivity in women depends on menstrual cycle phase (2023) · cites this paper as [11]
In pancreatic clamps with a primed, constant infusion of glucose tracers, IN administration of 40 IU insulin lispro compared with placebo suppressed endogenous glucose production only in normal-weight participants.
“In the latter set of experiments, 83,84 the IN administration of 40 IU of insulin lispro, another rapid-acting insulin analogue, in comparison with placebo, suppressed endogenous glucose production only in the normal-weight participants.”
From Intranasal insulin (2021) · cites this paper as [83]
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- Authors
- Dash, S., Xiao, C., Morgantini, C., Koulajian, K., & Lewis, G. F.
- Affiliations
- University of Toronto (CA)
- Corresponding author
- Lewis, Gary F.
- Venue
- Diabetes
- Publisher
- American Diabetes Association
- Published
- 2014-10-06
- Volume
- 64
- Issue
- 3
- Pages
- 766-774
- ISSN
- 0012-1797 (ISSN-L)
- 1939-327X
- OpenAlex
- W2136915688
- Cited by
- 108
- References
- 28
- Citations by year
- 2026: 3 · 2025: 4 · 2024: 12 · 2023: 5 · 2022: 6 · 2021: 14 · 2020: 10 · 2019: 12 · 2018: 6 · 2017: 16 · 2016: 7 · 2015: 12 · 2014: 1
- FWCI
- 11.90
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Diabetes (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Eli Lilly and Company (F3Z-CA-O082)
- Topics
- Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Keywords
- intranasal insulin, endogenous glucose production, hepatic glucose production, cerebrospinal fluid insulin, deuterated glucose, normoglycemia, diabetes treatment, liver glucose production
- MeSH terms
- Administration, Intranasal, Blood Glucose, Glucose, Humans, Hypoglycemic Agents, Insulin, Liver, Male, Middle Aged, Single-Blind Method, Cross-Over Studies, Healthy Volunteers
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