ArticleDiabetes2011
Brain GLP-1 signaling regulates femoral artery blood flow and insulin sensitivity through hypothalamic PKC-δ.
Article in Diabetes, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 40 citations in OpenAlex.
- Anatomical evidence links the stomach to the central amygdala, a region responsive to local GLP-1R agonist induced feeding and nausea-like behaviors in male mice.Frontiers in endocrinology · 2026Article
- Impacts of different pancreatic resection ranges on endocrine function inWorld journal of gastrointestinal surgery · 2024Article
- Glucagon-like peptide-1 (GLP-1) receptor agonists and their cardiovascular benefits-The role of the GLP-1 receptor.British journal of pharmacology · 2022Review
- Parallel genomic responses to historical climate change and high elevation in East Asian songbirds.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Lessons from bariatric surgery: Can increased GLP-1 enhance vascular repair during cardiometabolic-based chronic disease?Reviews in endocrine & metabolic disorders · 2021Review
- Brain Endothelial Cells Regulate Glucagon-Like Peptide 1 Entry Into the Brain via a Receptor-Mediated Process.Frontiers in physiology · 2020Article
- Exendin-4 overcomes cytokine-induced decreases in gap junction coupling via protein kinase A and Epac2 in mouse and human islets.The Journal of physiology · 2019Article
- Effects of GIP on regional blood flow during normoglycemia and hyperglycemia in anesthetized rats.Physiological reports · 2018Article
- GLP-1 Improves Adipocyte Insulin Sensitivity Following Induction of Endoplasmic Reticulum Stress.Frontiers in pharmacology · 2018 · on this mapArticle
- Acute activation of GLP-1-expressing neurons promotes glucose homeostasis and insulin sensitivity.Molecular metabolism · 2017Article
- Duodenal GLP-1 signaling regulates hepatic glucose production through a PKC-δ-dependent neurocircuitry.Cell death & disease · 2017Article
- GLP-1 Agonists and Blood Pressure: A Review of the Evidence.Current hypertension reports · 2016Review
- Brain GLP-1 and insulin sensitivity.Molecular and cellular endocrinology · 2015Review
- Dissociation of GLP-1 and insulin association with food processing in the brain: GLP-1 sensitivity despite insulin resistance in obese humans.Molecular metabolism · 2015Article
- SOCS3 deficiency in leptin receptor-expressing cells mitigates the development of pregnancy-induced metabolic changes.Molecular metabolism · 2015Article
- Inactivation of SOCS3 in leptin receptor-expressing cells protects mice from diet-induced insulin resistance but does not prevent obesity.Molecular metabolism · 2014Article
- Direct cardiovascular effects of glucagon like peptide-1.Diabetology & metabolic syndrome · 2013Article
- Green tea polyphenols alleviate early BBB damage during experimental focal cerebral ischemia through regulating tight junctions and PKCalpha signaling.BMC complementary and alternative medicine · 2013Article
- Neonatal exendin-4 reduces growth, fat deposition and glucose tolerance during treatment in the intrauterine growth-restricted lamb.PloS one · 2013Article
- The glucagon-like peptide-1 receptor agonist Exendin 4 has a protective role in ischemic injury of lean and steatotic liver by inhibiting cell death and stimulating lipolysis.The American journal of pathology · 2012Article
Corrections and comments
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Authors and funding
5 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectiveGlucagon-like peptide 1 (GLP-1) is a gut-brain hormone that regulates food intake, energy metabolism, and cardiovascular functions. In the brain, through a currently unknown molecular mechanism, it simultaneously reduces femoral artery blood flow and muscle glucose uptake. By analogy to pancreatic β-cells where GLP-1 activates protein kinase C (PKC) to stimulate insulin secretion, we postulated that PKC enzymes would be molecular targets of brain GLP-1 signaling that regulate metabolic and vascular function. RESEARCH DESIGN AND
methodsWe used both genetic and pharmacological approaches to investigate the role of PKC isoforms in brain GLP-1 signaling in the conscious, free-moving mouse simultaneous with metabolic and vascular measurements.
resultsIn normal wild-type (WT) mouse brain, the GLP-1 receptor (GLP-1R) agonist exendin-4 selectively promotes translocation of PKC-δ (but not -βII, -α, or -ε) to the plasma membrane. This translocation is blocked in Glp1r(-/-) mice and in WT mice infused in the brain with exendin-9, an antagonist of the GLP-1R. This mechanism coordinates both blood flow in the femoral artery and whole-body insulin sensitivity. Consequently, in hyperglycemic, high-fat diet-fed diabetic mice, hypothalamic PKC-δ activity was increased and its pharmacological inhibition improved both insulin-sensitive metabolic and vascular phenotypes.
conclusionsOur studies show that brain GLP-1 signaling activates hypothalamic glucose-dependent PKC-δ to regulate femoral artery blood flow and insulin sensitivity. This mechanism is attenuated during the development of experimental hyperglycemia and may contribute to the pathophysiology of type 2 diabetes.
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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.