FGF1 and FGF19 reverse diabetes by suppression of the hypothalamic–pituitary–adrenal axis
Open accessAbstract
Fibroblast growth factor-1 (FGF1) and FGF19 have been shown to improve glucose metabolism in diabetic rodents, but how this occurs is unknown. Here to investigate the mechanism of action of these growth factors, we perform intracerebroventricular (i.c.v.) injections of recombinant FGF1 or FGF19 in an awake rat model of type 1 diabetes (T1D) and measure rates of whole-body lipolysis, hepatic acetyl CoA content, pyruvate carboxylase activity and hepatic glucose production. We show that i.c.v. injection of FGF19 or FGF1 leads to a ∼60% reduction in hepatic glucose production, hepatic acetyl CoA content and whole-body lipolysis, which results from decreases in plasma ACTH and corticosterone concentrations. These effects are abrogated by an intra-arterial infusion of corticosterone. Taken together these studies identify suppression of the HPA axis and ensuing reductions in hepatic acetyl CoA content as a common mechanism responsible for mediating the acute, insulin-independent, glucose-lowering effects of FGF1 and FGF19 in rodents with poorly controlled T1D.
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Cholestasis is associated with suppression of the HPA axis, likely due to BA interactions with glucocorticoid receptors in the brain.
“Cholestasis, associated with suppression of the HPA axis, likely due to BA interactions with glucocorticoid receptors in the brain (299, 312).”
From Signalling cognition: The gut microbiota and hypothalamic-pituitary-adrenal axis (2023) · cites this paper as [312]
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References 22 · Cited by 132
- Authors
- Perry, R. J., Lee, S., Ma, L., Zhang, D., Schlessinger, J., & Shulman, G. I.
- Affiliations
- Howard Hughes Medical Institute (US)
- Yale University (US)
- Corresponding author
- Shulman, Gerald I.
- Venue
- Nature Communications
- Published
- 2015-04-28
- Volume
- 6
- Issue
- 1
- Pages
- 6980-6980
- ISSN
- 2041-1723 (ISSN-L)
- PMC
- PMC4413509
- OpenAlex
- W2011265302
- Cited by
- 132
- References
- 22
- Citations by year
- 2026: 6 · 2025: 13 · 2024: 14 · 2023: 8 · 2022: 13 · 2021: 17 · 2020: 8 · 2019: 13 · 2018: 13 · 2017: 15 · 2016: 7 · 2015: 5
- FWCI
- 5.79
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Nature Communications (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- Howard Hughes Medical Institute
- Novo Nordisk
- Novo Nordisk Fonden
- Novo Nordisk Foundation Center for Basic Metabolic Research
- National Institutes of Health (P30 DK, R24 DK-085638, DK059635, DK-085638, DK-45735)
- National Institute of Diabetes and Digestive and Kidney Diseases (P30DK45735, T32DK101019, R01-DK40936, R01DK040936, U24DK059635, R24DK085638, P30DK045735)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fibroblast Growth Factor Research
- Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Keywords
- fibroblast growth factor 1, FGF19, type 1 diabetes, hypothalamic-pituitary-adrenal axis, hepatic glucose production, acetyl-CoA, pyruvate carboxylase, lipolysis, ACTH, corticosterone, glucose metabolism, insulin-independent glucose lowering
- MeSH terms
- Acetyl Coenzyme A, Adrenocorticotropic Hormone, Animals, Corticosterone, Diabetes Mellitus, Experimental, Diabetes Mellitus, Type 1, Fibroblast Growth Factors, Glucose, Hypothalamo-Hypophyseal System, Injections, Intraventricular, Insulin, Lipolysis, Liver, Male, Pituitary-Adrenal System, Pyruvate Carboxylase, Fibroblast Growth Factor 1, Rats, Sprague-Dawley
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