Circulating PANDER concentration is associated with increased HbA1c and fasting blood glucose in Type 2 diabetic subjects

MarElia, Catherine B.; Kuehl, Melanie N.; Shemwell, Tiffany A.; Alman, Amy C.; Burkhardt, Brant R.

doi:10.1016/j.jcte.2018.02.003

Cited by 4 publications

(7 citation statements)

References 25 publications

(34 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Another clinical report confirmed that serum PANDER level is increased in patients with metabolic syndrome, and an increase in circulating PANDER level can predict metabolic syndrome in Chinese population . An increase in serum PANDER levels have been reported to be associated with pancreatic β cell dysfunction and hyperglycemia in other races . Overall, these important clinical studies revealed that circulating PANDER is a unique diagnostic biomarker for diabetes and metabolic syndrome, and it is necessary to further study the mechanism(s) of PANDER in the regulation of glucose and lipid metabolism.…”

Section: Discussionmentioning

confidence: 81%

“…29 An increase in serum PANDER levels have been reported to be associated with pancreatic β cell dysfunction and hyperglycemia in other races. 18,19 Overall, these important clinical studies revealed that circulating PANDER is a unique diagnostic biomarker for diabetes and metabolic syndrome, and it is necessary to further study the mechanism(s) of PANDER in the regulation of glucose and lipid metabolism.…”

Section: Discussionmentioning

confidence: 99%

“…15,16 In humans, increased circulating PANDER levels have been reported to be associated with pancreatic β cell dysfunction, hyperglycemia and insulin resistance in various races. [17][18][19] Overall, these clinical and experimental studies had established that PANDER plays important roles in the regulation of glucose and lipid metabolism. [17][18][19][20] In the previous study, 13 we demonstrated that PANDER promotes the lipogenesis in hepatocytes by inhibiting Akt to activate FOXO1.…”

Section: Introductionmentioning

confidence: 98%

“…[17][18][19] Overall, these clinical and experimental studies had established that PANDER plays important roles in the regulation of glucose and lipid metabolism. [17][18][19][20] In the previous study, 13 we demonstrated that PANDER promotes the lipogenesis in hepatocytes by inhibiting Akt to activate FOXO1. However, whether PANDER activates FOXO1 activity via other mechanism(s) beyond Akt repression remains unknown.…”

Section: Introductionmentioning

confidence: 98%

See 3 more Smart Citations

FAM3B (PANDER) functions as a co‐activator of FOXO1 to promote gluconeogenesis in hepatocytes

Chi

Meng

Wang

et al. 2018

J Cellular Molecular Medi

View full text Add to dashboard Cite

FAM3B, also known as PANcreatic DERived factor (PANDER), promotes gluconeogenesis and lipogenesis in hepatocytes. However, the underlying mechanism(s) still remains largely unclear. This study determined the mechanism of PANDER‐induced FOXO1 activation in hepatocytes. In mouse livers and cultured hepatocytes, PANDER protein is located in both the cytoplasm and nucleus. Nuclear PANDER distribution was increased in the livers of obese mice. In cultured mouse and human hepatocytes, PANDER was co‐localized with FOXO1 in the nucleus. PANDER directly interacted with FOXO1 in mouse and human hepatocytes. PANDER overexpression enhanced PANDER‐FOXO1 interaction, and detained FOXO1 in the nucleus upon insulin stimulation in hepatocytes. With the increase in PANDER‐FOXO1 interaction, PANDER overexpression upregulated the expression of gluconeogenic genes and promoted gluconeogenesis in both human and mouse hepatocytes. Luciferase reporter assays further revealed that PANDER augmented the transcriptional activity of FOXO1 on gluconeogenic genes. Moreover, PANDER overexpression also interfered the binding of AS1842856, a specific FOXO1 inhibitor, with FOXO1, and impaired its inhibitory effects on gluconeogenic gene expression and gluconeogenesis in hepatocytes. siRNA mediated‐silencing of FOXO1 inhibited PANDER‐promoted gluconeogenic gene expression and glucose production in hepatocytes. In conclusion, PANDER protein is abundantly present in the nucleus, where it functions as a new co‐activator of FOXO1 to induce gluconeogenic gene expression in hepatocytes.

show abstract

Section: Discussionmentioning

confidence: 81%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 98%

See 2 more Smart Citations

FAM3B (PANDER) functions as a co‐activator of FOXO1 to promote gluconeogenesis in hepatocytes

Chi

Meng

Wang

et al. 2018

J Cellular Molecular Medi

View full text Add to dashboard Cite

show abstract

“…First, FAM3B has been suggested to be a causal gene for type 2 diabetes. In humans and mice, increased circulating FAM3B/PANDER levels are associated with hyperglycemia, pancreatic β-cell dysfunction, and insulin resistance (54)(55)(56)(57)(58). Second, FAM3B has been reported to act as an oncogene that, when expressed, promotes the progression of several types of cancer, including colon cancer, prostate cancer, esophageal cancer, and gastric cancer (20)(21)(22)(23).…”

Section: Discussionmentioning

confidence: 99%

The cytokine FAM3B/PANDER is an FGFR ligand that promotes posterior development in Xenopus

Zhang

Zhu

Wang

et al. 2021

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Fibroblast growth factor (FGF)/extracellular signal-regulated kinase (ERK) signaling plays a crucial role in anterior–posterior (A–P) axial patterning of vertebrate embryos by promoting posterior development. In our screens for novel developmental regulators in Xenopus embryos, we identified Fam3b as a secreted factor regulated in ectodermal explants. Family with sequence similarity 3 member B (FAM3B)/PANDER (pancreatic-derived factor) is a cytokine involved in glucose metabolism, type 2 diabetes, and cancer in mammals. However, the molecular mechanism of FAM3B action in these processes remains poorly understood, largely because its receptor is still unidentified. Here we uncover an unexpected role of FAM3B acting as a FGF receptor (FGFR) ligand in Xenopus embryos. fam3b messenger RNA (mRNA) is initially expressed maternally and uniformly in the early Xenopus embryo and then in the epidermis at neurula stages. Overexpression of Xenopus fam3b mRNA inhibited cephalic structures and induced ectopic tail-like structures. Recombinant human FAM3B protein was purified readily from transfected tissue culture cells and, when injected into the blastocoele cavity, also caused outgrowth of tail-like structures at the expense of anterior structures, indicating FGF-like activity. Depletion of fam3b by specific antisense morpholino oligonucleotides in Xenopus resulted in macrocephaly in tailbud tadpoles, rescuable by FAM3B protein. Mechanistically, FAM3B protein bound to FGFR and activated the downstream ERK signaling in an FGFR-dependent manner. In Xenopus embryos, FGFR activity was required epistatically downstream of Fam3b to mediate its promotion of posterior cell fates. Our findings define a FAM3B/FGFR/ERK-signaling pathway that is required for axial patterning in Xenopus embryos and may provide molecular insights into FAM3B-associated human diseases.

show abstract

Relationship between Cytokines and Metabolic Syndrome Components: Role of Pancreatic-Derived Factor, Interleukin-37, and Tumor Necrosis Factor-α in Metabolic Syndrome Patients

et al. 2022

View full text Add to dashboard Cite

Circulating PANDER concentration is associated with increased HbA1c and fasting blood glucose in Type 2 diabetic subjects

Cited by 4 publications

References 25 publications

FAM3B (PANDER) functions as a co‐activator of FOXO1 to promote gluconeogenesis in hepatocytes

FAM3B (PANDER) functions as a co‐activator of FOXO1 to promote gluconeogenesis in hepatocytes

The cytokine FAM3B/PANDER is an FGFR ligand that promotes posterior development in Xenopus

Relationship between Cytokines and Metabolic Syndrome Components: Role of Pancreatic-Derived Factor, Interleukin-37, and Tumor Necrosis Factor-α in Metabolic Syndrome Patients

Contact Info

Product

Resources

About