ArticleThe Journal of clinical investigation2000
Regulation of pancreatic PC1 and PC2 associated with increased glucagon-like peptide 1 in diabetic rats.
Article in The Journal of clinical investigation, 2000. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 72 papers.
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Who cites it
72 citing papers in PubMed, 168 citations in OpenAlex.
- β-cell 14-3-3-ζ and sex are key regulators of α-cell form and function.Endocrinology · 2026Article
- Pancreatic Islet Cell Crosstalk: Insight Into α-/β-Cell Compensatory Mechanisms.Comprehensive Physiology · 2026Article
- α cells use both PC1/3 and PC2 to process proglucagon peptides and control insulin secretion.Science advances · 2025Article
- Integrative analysis of DEGs and regulatory networks in T2DM: identification of core genes and regulatory elements as novel therapeutic targets.3 Biotech · 2025Article
- Islet hormones at the intersection of glucose and amino acid metabolism.Nature reviews. Endocrinology · 2025Review
- Cystic fibrosis-related diabetes is associated with reduced islet protein expression of GLP-1 receptor and perturbation of cell-specific transcriptional programs.Scientific reports · 2024Article
- GLP-1 receptor agonist-based therapies and cardiovascular risk: a review of mechanisms.The Journal of endocrinology · 2024Review
- Evaluating glucose-dependent insulinotropic polypeptide and glucagon as key regulators of insulin secretion in the pancreatic islet.American journal of physiology. Endocrinology and metabolism · 2024Review
- The Importance of Intra-Islet Communication in the Function and Plasticity of the Islets of Langerhans during Health and Diabetes.International journal of molecular sciences · 2024Review
- Acute Inhibition of Intestinal Neprilysin Enhances Insulin Secretion via GLP-1 Receptor Signaling in Male Mice.Endocrinology · 2023Article
- The role of preproglucagon peptides in regulating β-cell morphology and responses to streptozotocin-induced diabetes.American journal of physiology. Endocrinology and metabolism · 2023Article
- 14-3-3-zeta mediates GLP-1 receptor agonist action to alter α cell proglucagon processing.Science advances · 2022Article
- The Essential Role of Pancreatic α-Cells in Maternal Metabolic Adaptation to Pregnancy.Diabetes · 2022Article
- Neprilysin inhibition improves intravenous but not oral glucose-mediated insulin secretion via GLP-1R signaling in mice withAmerican journal of physiology. Endocrinology and metabolism · 2022Article
- Alpha-cell paracrine signaling in the regulation of beta-cell insulin secretion.Frontiers in endocrinology · 2022Review
- Glucagon's Metabolic Action in Health and Disease.Comprehensive Physiology · 2021Article
- Revisiting the Complexity of GLP-1 Action from Sites of Synthesis to Receptor Activation.Endocrine reviews · 2021Review
- Review
- Article
- Pathways of Glucagon Secretion and Trafficking in the Pancreatic Alpha Cell: Novel Pathways, Proteins, and Targets for Hyperglucagonemia.Frontiers in endocrinology · 2021Review
12 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 5 institutions in 4 countries.
Funding
Abstract
The pancreatic processing enzymes, PC1 and PC2, convert proinsulin to insulin and convert proglucagon to glucagon and glucagon-like peptide 1 (GLP-1). We examined the effect of streptozotocin (STZ) treatment on the regulation of these enzymes and the production of insulin, glucagon, and GLP-1 in the rat. Pancreatic PC1 and PC2 mRNA increased >2-fold and >4-fold, respectively, in rats receiving intraperitoneal STZ (50 mg/kg) daily for 5 days. Immunocytochemistry revealed that, although pancreatic islet cells in the STZ-treated rats were sparse and atrophic PC1, PC2, glucagon, and GLP-1 immunoreactivity increased dramatically in the remaining islet cells. Heightened PC1 and PC2 expression was seen in cells expressing glucagon but not in insulin-expressing cells. Furthermore, in STZ-treated rats, bioactive GLP-1(7-36 amide) accumulated in pancreatic extracts and serum 3- and 2.5-fold, respectively, over control animals. This treatment also caused a 2-fold increase in the ratio of amidated forms of GLP-1 immunoreactivity to total glucagon immunoreactivity in the pancreas but did not affect the ratio of proinsulin to insulin. We conclude that hyperglycemic rats have an increased expression of prohormone converting enzymes in islet alpha cells, leading to an increase in amidated GLP-1, which can then exert an insulinotropic effect on the remaining beta cells.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.