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Cited by 22Pancreatic function and diabetesAdipokines, Inflammation, and Metabolic DiseasesMetabolism, Diabetes, and Cancer

Enhanced glucose tolerance in pancreatic derived factor (PANDER) knockout C57BL/6 mice

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Moak, Shari L., Dougan, Grace C., MarElia, Catherine B., Danse, Whitney A., Fernandez, Amanda M., Kuehl, Melanie N., Athanason, Mark G., Burkhardt, Brant R.·2014·Disease Models & Mechanisms
DOI 10.1242/dmm.016402PMC PMC4213734
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Abstract

PANcreatic-DERived Factor (PANDER, FAM3B) is a uniquely structured protein strongly expressed within and secreted from the endocrine pancreas. PANDER has been hypothesized to regulate fasting and fed glucose homeostasis, hepatic lipogenesis and insulin signaling, and serve a potential role in the onset or progression of type 2 diabetes. Despite having a potential pleiotropic pivotal role in glycemic regulation and T2D, there has been limited generation of stable animal models for PANDER investigation, with none on well-established genetic murine backgrounds for T2D. Our aim was to generate an enhanced murine model to further elucidate the biological function of PANDER. Therefore, a pure bred PANDER C57BL/6 knockout model (PANKO-C57) was created and phenotypically characterized with respect to glycemic regulation and hepatic insulin signaling. The PANKO-C57 exhibited an enhanced metabolic phenotype particularly with regard to enhanced glucose tolerance. Male PANKO-C57 mice displayed decreased fasting plasma insulin and c-peptide levels, whereas leptin levels were increased as compared to matched C57BL/6J WT mice. Despite similar peripheral insulin sensitivity between both groups, hepatic insulin signaling was significantly increased during fasting conditions as demonstrated by increased phosphorylation of hepatic Akt and AMPK along with mature SREBP-1 expression. Insulin stimulation of PANKO-C57 mice resulted in increased hepatic triglyceride and glycogen content as compared to C57BL/6 WT. In summary, the PANKO-C57 mouse represents a suitable model for the investigation of PANDER in multiple metabolic states and provides an additional tool to elucidate the biological function and potential role in T2D.

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Authors
Moak, S. L., Dougan, G. C., MarElia, C. B., Danse, W. A., Fernandez, A. M., Kuehl, M. N., Athanason, M. G., & Burkhardt, B. R.
Affiliations
University of South Florida (US)
Corresponding author
Burkhardt, Brant R.
ORCID
Venue
Disease Models & Mechanisms
Publisher
The Company of Biologists
Published
2014-01-01
Volume
7
Issue
11
Pages
1307-15
ISSN
  • 1754-8403 (ISSN-L)
  • 1754-8411
DOI
10.1242/dmm.016402
PMC
PMC4213734
OpenAlex
W2164495199
Cited by
22
References
0
Citations by year
2023: 2 · 2021: 2 · 2020: 1 · 2019: 2 · 2018: 4 · 2017: 5 · 2016: 2 · 2015: 4
FWCI
3.63
Type
journal article
Language
en
Open access
Licence
Locations
  • Disease Models & Mechanisms (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • HighWire Press Open Archive (submittedVersion)
Funders
University of South Florida
Topics
  • Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
  • Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
Keywords
FAM3B, type 2 diabetes, glucose tolerance, hepatic insulin signaling, hepatic lipogenesis, hepatic triglycerides, liver glycogen, Akt, AMPK, SREBP1, insulin resistance, leptin, pancreatic endocrine cells, C57BL/6 mice
MeSH terms
Animals, Female, Glucose Tolerance Test, Insulin, Male, Mice, Inbred C57BL, Cytokines, Mice, Knockout, Mice

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