Early postnatal activation of the hypoxia pathway disrupts β-cell function Article Swipe
Juxiang Yang
,
Batoul Hammoud
,
Abigail Ridler
,
Kyoung‐Jae Won
,
Toshinori Hoshi
,
Charles A. Stanley
,
Diana E. Stanescu
,
Amanda M. Ackermann
·
YOU?
·
· 2021
· Open Access
·
· DOI: https://doi.org/10.1101/2021.06.09.447705
YOU?
·
· 2021
· Open Access
·
· DOI: https://doi.org/10.1101/2021.06.09.447705
Hypoxic insults in the perinatal period can lead to persistent hyperinsulinism and profound hypoglycemia in newborns. We studied the impact of the hypoxia-inducible factor 1A (HIF1A) pathway on postnatal β-cell function. Rat pups were treated daily between postnatal day (P)7 to P10 with adaptaquin (AQ), an inhibitor of prolyl hydroxylases, which stabilizes HIF1A. AQ-treated pups were hypoglycemic and had higher plasma insulin concentrations. Their islets had a decreased glucose threshold for insulin secretion, indicative of a delay in β-cell postnatal functional maturation. Histology analyses revealed that AQ-treated pups had increased pancreatic insulin-positive area but no changes in the number of islets or number of β-cells per islet, suggesting larger average β-cell size. AQ-treated rat pups had decreased expression of cell cycle genes and decreased numbers of proliferating β-cells. In conclusion, pharmacologic activation of the HIF1A pathway in the early postnatal period leads to hyperinsulinism, due to the persistence of a low glucose threshold for insulin secretion, and to decreased early postnatal β-cell proliferation, suggesting it can impact adult β-cell mass and diabetes risk.
Related Topics
Concepts
Internal medicine
Endocrinology
Insulin
HIF1A
Hypoglycemia
Islet
Hypoxia (environmental)
Biology
Hyperinsulinism
Insulin oscillation
Medicine
Chemistry
Insulin resistance
Angiogenesis
Organic chemistry
Oxygen
Metadata
- Type
- preprint
- Language
- en
- Landing Page
- https://doi.org/10.1101/2021.06.09.447705
- https://www.biorxiv.org/content/biorxiv/early/2021/10/12/2021.06.09.447705.full.pdf
- OA Status
- green
- Cited By
- 4
- References
- 55
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W3166332409
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W3166332409Canonical identifier for this work in OpenAlex
- DOI
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https://doi.org/10.1101/2021.06.09.447705Digital Object Identifier
- Title
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Early postnatal activation of the hypoxia pathway disrupts β-cell functionWork title
- Type
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preprintOpenAlex work type
- Language
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enPrimary language
- Publication year
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2021Year of publication
- Publication date
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2021-06-09Full publication date if available
- Authors
-
Juxiang Yang, Batoul Hammoud, Abigail Ridler, Kyoung‐Jae Won, Toshinori Hoshi, Charles A. Stanley, Diana E. Stanescu, Amanda M. AckermannList of authors in order
- Landing page
-
https://doi.org/10.1101/2021.06.09.447705Publisher landing page
- PDF URL
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https://www.biorxiv.org/content/biorxiv/early/2021/10/12/2021.06.09.447705.full.pdfDirect link to full text PDF
- Open access
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YesWhether a free full text is available
- OA status
-
greenOpen access status per OpenAlex
- OA URL
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https://www.biorxiv.org/content/biorxiv/early/2021/10/12/2021.06.09.447705.full.pdfDirect OA link when available
- Concepts
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Internal medicine, Endocrinology, Insulin, HIF1A, Hypoglycemia, Islet, Hypoxia (environmental), Biology, Hyperinsulinism, Insulin oscillation, Medicine, Chemistry, Insulin resistance, Angiogenesis, Organic chemistry, OxygenTop concepts (fields/topics) attached by OpenAlex
- Cited by
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4Total citation count in OpenAlex
- Citations by year (recent)
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2024: 1, 2023: 2, 2022: 1Per-year citation counts (last 5 years)
- References (count)
-
55Number of works referenced by this work
- Related works (count)
-
10Other works algorithmically related by OpenAlex
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