ArticleMolecular endocrinology (Baltimore, Md.)2009
Mice deficient for glucagon gene-derived peptides display normoglycemia and hyperplasia of islet {alpha}-cells but not of intestinal L-cells.
Article in Molecular endocrinology (Baltimore, Md.), 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers.
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Who cites it
66 citing papers in PubMed, 111 citations in OpenAlex.
- Adrenal hormones in the maintenance of glucose homeostasis during prolonged fasting in male glucagon-deficient mice.Journal of diabetes investigation · 2026Article
- Alpha-cell glucagon is essential for maintaining β-cell function and identity in adult mice.The Journal of biological chemistry · 2026Article
- SEL1L-HRD1 ER-associated degradation facilitates prohormone convertase 2 maturation and glucagon production in islet α cells.Nature communications · 2026Article
- Liver-specific glucagon dysfunction promotes PP-cell hyperplasia and formation of glucagon and PP double-positive cells.PloS one · 2025Article
- Article
- Impaired Fat Absorption from Intestinal Tract in High-Fat Diet Fed Male Mice Deficient in Proglucagon-Derived Peptides.Nutrients · 2024Article
- Advances in basic research on glucagon and alpha cells.Diabetology international · 2024Review
- Downregulation of the kidney glucagon receptor, essential for renal function and systemic homeostasis, contributes to chronic kidney disease.Cell metabolism · 2024Article
- Novel time-resolved reporter mouse reveals spatial and transcriptional heterogeneity during alpha cell differentiation.Diabetologia · 2024Article
- Article
- Blockade of glucagon increases muscle mass and alters fiber type composition in mice deficient in proglucagon-derived peptides.Journal of diabetes investigation · 2023Article
- Not the second fiddle: α cell development, identity, and function in health and diabetes.The Journal of endocrinology · 2023Review
- Models in Pancreatic Neuroendocrine Neoplasms: Current Perspectives and Future Directions.Cancers · 2023Review
- A newly developed glucagon sandwich ELISA is useful for more accurate glucagon evaluation than the currently used sandwich ELISA in subjects with elevated plasma proglucagon-derived peptide levels.Journal of diabetes investigation · 2023Article
- Recent progress of experimental model in pancreatic neuroendocrine tumors: drawbacks and challenges.Endocrine · 2023Review
- Hyperaminoacidemia induces pancreatic α cell proliferation via synergism between the mTORC1 and CaSR-Gq signaling pathways.Nature communications · 2023Article
- Exploring the Effects of Metabolism-Disrupting Chemicals on Pancreatic α-Cell Viability, Gene Expression and Function: A Screening Testing Approach.International journal of molecular sciences · 2023Article
- An analysis of intestinal morphology and incretin-producing cells using tissue optical clearing and 3-D imaging.Scientific reports · 2022Article
- The Essential Role of Pancreatic α-Cells in Maternal Metabolic Adaptation to Pregnancy.Diabetes · 2022Article
- Protein Kinase C (Pkc)-δ Mediates Arginine-Induced Glucagon Secretion in Pancreatic α-Cells.International journal of molecular sciences · 2022Article
6 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Multiple bioactive peptides, including glucagon, glucagon-like peptide-1 (GLP-1), and GLP-2, are derived from the glucagon gene (Gcg). In the present study, we disrupted Gcg by introduction of GFP cDNA and established a knock-in mouse line. Gcg(gfp/gfp) mice that lack most, if not all, of Gcg-derived peptides were born in an expected Mendelian ratio without gross abnormalities. Gcg(gfp/gfp) mice showed lower blood glucose levels at 2 wk of age, but those in adult Gcg(gfp/gfp) mice were not significantly different from those in Gcg(+/+) and Gcg(gfp/+) mice, even after starvation for 16 h. Serum insulin levels in Gcg(gfp/gfp) mice were lower than in Gcg(+/+) and Gcg(gfp/+) on ad libitum feeding, but no significant differences were observed on starvation. Islet alpha-cells and intestinal L-cells were readily visualized in Gcg(gfp/gfp) and Gcg(gfp/+) mice under fluorescence. The Gcg(gfp/gfp) postnatally developed hyperplasia of islet alpha-cells, whereas the population of intestinal L-cells was not increased. In the Gcg(gfp/gfp), expression of Aristaless-related homeobox (Arx) was markedly increased in pancreas but not in intestine and suggested involvement of Arx in differential regulation of proliferation of Gcg-expressing cells. These results illustrated that Gcg-derived peptides are dispensable for survival and maintaining normoglycemia in adult mice and that Gcg-derived peptides differentially regulate proliferation/differentiation of alpha-cells and L-cells. The present model is useful for analyzing glucose/energy metabolism in the absence of Gcg-derived peptides. It is useful also for analysis of the development, differentiation, and function of Gcg-expressing cells, because such cells are readily visualized by fluorescence in this model.
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