Back to Search
Start Over
Liver-Specific Overexpression of Pancreatic-Derived Factor (PANDER) Induces Fasting Hyperglycemia in Mice
- Source :
- Endocrinology. 151:5174-5184
- Publication Year :
- 2010
- Publisher :
- The Endocrine Society, 2010.
-
Abstract
- The pancreas-derived hormones, insulin and glucagon, are the two main regulators of glucose homeostasis. However, their actions can be modulated by the presence of other circulating factors including cytokines. Pancreatic-derived factor (PANDER) is a novel cytokine-like molecule secreted from the endocrine pancreas, but its biological function is currently unknown. To address this, we employed adenoviral gene delivery to develop a novel murine model of PANDER overexpression, which we used to study PANDER’s effect on glucose homeostasis. Although serum metabolites in fed mice were unaffected by PANDER overexpression, fasting glucose, insulin, and corticosterone levels were significantly elevated. Additionally, PANDER-overexpressing mice displayed elevated glucose and insulin levels during a glucose tolerance test, indicating that glucose tolerance was impaired. However, there were no defects in glucose-stimulated insulin secretion or peripheral insulin sensitivity. Elevated transcription of hepatic gluconeogenic genes, PEPCK and G6Pase accompanied the fasting hyperglycemia observed in PANDER-overexpressing animals. Similarly, treatment of primary hepatocytes with PANDER-expressing adenovirus or PANDER-enriched conditioned medium elevated gluconeogenic gene expression and glucose output. PANDER treatment also resulted in higher levels of Ser133-phosphorylated cAMP-response element-binding protein in hepatocytes stimulated with 8-bromo-cAMP and dexamethasone and higher levels of intracellular cAMP upon stimulation with forskolin. In summary, we provide the first report that identifies PANDER as a regulator of hepatic glucose metabolism, where it serves as a novel factor that amplifies hepatic cAMP and cAMP-response element-binding protein signaling to induce gluconeogenic gene expression and glucose output.
- Subjects :
- Blood Glucose
Male
medicine.medical_specialty
medicine.medical_treatment
Blotting, Western
Gene Expression
Mice, Transgenic
Biology
Glucagon
Article
Adenoviridae
Mice
chemistry.chemical_compound
Endocrinology
Internal medicine
Cyclic AMP
medicine
Animals
Insulin
Glucose homeostasis
Cyclic AMP Response Element-Binding Protein
Glucose tolerance test
Forskolin
medicine.diagnostic_test
Reverse Transcriptase Polymerase Chain Reaction
Fasting
Metabolism
Glucose Tolerance Test
Liver
chemistry
Culture Media, Conditioned
Hyperglycemia
Hepatocytes
Cytokines
Insulin Resistance
Signal transduction
Signal Transduction
Hormone
Subjects
Details
- ISSN :
- 19457170 and 00137227
- Volume :
- 151
- Database :
- OpenAIRE
- Journal :
- Endocrinology
- Accession number :
- edsair.doi.dedup.....ae7bb9e46d49ef44f8a8d61126307110
- Full Text :
- https://doi.org/10.1210/en.2010-0379