Central Regulation of Glucose Metabolism in Humans: Fact or Fiction?
Abstract
In the past few years, insulin action in the central nervous system (CNS) has attracted a growing interest to better understand the association between neurodegenerative diseases and insulin resistance (IR). Rodent studies have indicated that insulin signaling in the CNS is critical for the suppression of endogenous glucose production (EGP) in the liver (1) and for the regulation of adipose tissue lipolysis (2). These central insulin effects likely depend on PI3K-mediated regulation of several proteins and transcription factors, among which are FoxO1 (3) and AMPK (4), and on the activation of KATP channels (5) in the hypothalamus (Fig. 1). Recent findings show that subsequent activation of hepatic Kupffer cells and an increase in hepatic interleukin-6 induce signal transducer and activator of transcription 3 (STAT3) phosphorylation to inhibit gluconeogenic gene expression (6). Suppression of lipolysis in adipose tissue by brain insulin signaling reduces the availability of gluconeogenic substrates for the liver, which will further decrease EGP (2). In contrast, studies in dogs did not support the concept of a physiological relevance of CNS insulin action for controlling EGP (7). Figure 1 Brain insulin regulation of hepatic glucose production and adipose tissue lipolysis. The insulin-signaling pathway in the arcuate hypothalamus involves the activation of PI3K and AKT and the subsequent inactivation of FoxO1. Also, the inhibition of AMPK and opening of KATP channels are linked to brain insulin’s peripheral metabolic effects. In addition …
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Brain insulin action may require postprandial metabolic conditions.
“However, this may require postprandial metabolic conditions12,13”
From Brain insulin action on peripheral insulin sensitivity in women depends on menstrual cycle phase (2023) · cites this paper as [13]
Cites
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- Authors
- Gancheva, S., & Roden, M.
- Affiliations
- Deutsches Diabetes-Zentrum e.V. (DE)
- Corresponding author
- Roden, Michael
- Venue
- Diabetes
- Publisher
- American Diabetes Association
- Published
- 2016-08-13
- Volume
- 65
- Issue
- 9
- Pages
- 2467-2469
- ISSN
- 0012-1797 (ISSN-L)
- 1939-327X
- OpenAlex
- W2512013108
- Cited by
- 5
- References
- 17
- Citations by year
- 2023: 1 · 2021: 1 · 2020: 1 · 2018: 1 · 2017: 1
- FWCI
- 0.42
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Diabetes (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Keywords
- brain insulin signaling, glucose metabolism, hepatic glucose production, endogenous glucose production, adipose tissue lipolysis, hypothalamus, PI3K/Akt signaling, FOXO1, AMPK, ATP-sensitive potassium channels, STAT3, gluconeogenesis, insulin resistance, neurodegenerative diseases
- MeSH terms
- Blood Glucose, Humans, Carbohydrate Metabolism
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