ArticleJournal of molecular neuroscience : MN2010
Intra-islet PACAP protects pancreatic β-cells against glucotoxicity and lipotoxicity.
Article in Journal of molecular neuroscience : MN, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 29 citations in OpenAlex.
- Protective Effects of PACAP in Diabetic Complications: Retinopathy, Nephropathy and Neuropathy.International journal of molecular sciences · 2025Review
- Mitochondrial uncoupling protein 2: a central player in pancreatic disease pathophysiology.Molecular medicine (Cambridge, Mass.) · 2024Review
- Protective Effects of PACAP in a Rat Model of Diabetic Neuropathy.International journal of molecular sciences · 2021Article
- Lipotoxic Impairment of Mitochondrial Function in β-Cells: A Review.Antioxidants (Basel, Switzerland) · 2021Review
- Protective Effects of PACAP in Peripheral Organs.Frontiers in endocrinology · 2020Review
- The Neuropeptide Pituitary Adenylate Cyclase-Activating Polypeptide (PACAP) is Protective in Inflammation and Oxidative Stress-Induced Damage in the Kidney.International journal of molecular sciences · 2019Review
- Pituitary Adenylate Cyclase-Activating Polypeptide: 30 Years in Research Spotlight and 600 Million Years in Service.Journal of clinical medicine · 2019Review
- IL-10 gene transfer upregulates arcuate POMC and ameliorates hyperphagia, obesity and diabetes by substituting for leptin.International journal of obesity (2005) · 2016Article
- A novel insulinotropic mechanism of whole grain-derived γ-oryzanol via the suppression of local dopamine DBritish journal of pharmacology · 2015Article
- Role of ZAC1 in transient neonatal diabetes mellitus and glucose metabolism.World journal of biological chemistry · 2015Review
- Signaling molecules involved in lipid-induced pancreatic beta-cell dysfunction.DNA and cell biology · 2013Review
- PACAP Inhibits β-cell Mass Expansion in a Mouse Model of Type II Diabetes: Persistent Suppressive Effects on Islet Density.Frontiers in endocrinology · 2013Article
- PACAP is an endogenous protective factor-insights from PACAP-deficient mice.Journal of molecular neuroscience : MN · 2012Article
- PPARδ Activation Rescues Pancreatic β-Cell Line INS-1E from Palmitate-Induced Endoplasmic Reticulum Stress through Enhanced Fatty Acid Oxidation.PPAR research · 2012Article
- β-Arrestins: multifunctional signaling adaptors in type 2 diabetes.Molecular biology reports · 2011Review
- Trophic effects of PACAP on pancreatic islets: a mini-review.Journal of molecular neuroscience : MN · 2011Review
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Pituitary adenylate cyclase-activating polypeptide (PACAP), a potent insulinotropin, is localized in pancreatic islets. Hyperglycemia and hyperlipidemia impair islet β-cell functions, being recognized as glucotoxicity and lipotoxicity. In this study, we examined whether endogenous PACAP protects islet β-cells against the toxicities. Pancreatic islets were prepared from wild-type and PACAP-null mice, and cultured for 2 days in control conditions containing 5.6 mM glucose, those with elevated 25 mM glucose and those supplemented with 0.4 mM palmitate. After culture in control conditions, a rise in the superfusate glucose concentration from 2.8 mM to a physiologic 8.3 mM increased cytosolic Ca(2+) concentration ([Ca(2+)](i)) in both wild-type and PACAP-null mouse islets. In contrast, after culture with high glucose or palmitate, the glucose-induced first phase [Ca(2+)](i) increases were severely impaired in islets of PACAP-null mice while they were preserved in islets of wild-type mice. Treatment with high glucose or palmitate also impaired glucose-induced insulin secretion in islets and increased mRNA expression of uncoupling protein 2 (UCP2) in islets of PACAP-null, but not wild-type, mice. These data indicate that islet-produced PACAP protects β-cells from deteriorating action of high glucose and palmitate at least partly by blocking the elevation of UCP2, suggesting an anti-diabetic role for PACAP.
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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.