ArticleProceedings of the National Academy of Sciences of the United States of America2014
Hypothalamic prolyl endopeptidase (PREP) regulates pancreatic insulin and glucagon secretion in mice.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 18 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
18 citing papers in PubMed, 31 citations in OpenAlex.
- Prognostic and microenvironmental analysis of pancreatic cancer by tumor location.Discover oncology · 2025Article
- Novel prolyl endopeptidase inhibitor fromRSC advances · 2025Article
- Increased Expression of Prolyl Endopeptidase Induced by Oxidative Stress in Nucleus Pulposus Cells Aggravates Intervertebral Disc Degeneration.Oxidative medicine and cellular longevity · 2022Article
- Hepatic IGF2/H19 Epigenetic Alteration Induced Glucose Intolerance in Gestational Diabetes Mellitus OffspringFrontiers in endocrinology · 2022Article
- Prolyl endopeptidase gene disruption attenuates high fat diet-induced nonalcoholic fatty liver disease in mice by improving hepatic steatosis and inflammation.Annals of translational medicine · 2020Article
- Altered Central Nutrient Sensing in Male Mice Lacking Insulin Receptors in Glut4-Expressing Neurons.Endocrinology · 2019Article
- Subcellular Localization of Prolyl Endopeptidase During the First Wave of Rat Spermatogenesis and in Rat and Human Sperm.The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society · 2019Article
- Overexpression of melanocortin 2 receptor accessory protein 2 (MRAP2) in adult paraventricular MC4R neurons regulates energy intake and expenditure.Molecular metabolism · 2018Article
- Mitochondrial Dynamics and Hypothalamic Regulation of Metabolism.Endocrinology · 2018Article
- Autonomic Regulation of Glucose Homeostasis: a Specific Role for Sympathetic Nervous System Activation.Current diabetes reports · 2018Review
- New compounds identified through in silico approaches reduce the α-synuclein expression by inhibiting prolyl oligopeptidase in vitro.Scientific reports · 2017Article
- Hypothalamic Ventromedial Lin28a Enhances Glucose Metabolism in Diet-Induced Obesity.Diabetes · 2017Article
- DRP1 Suppresses Leptin and Glucose Sensing of POMC Neurons.Cell metabolism · 2017Article
- Mechanism of Action of Prolyl Oligopeptidase (PREP) in Degenerative Brain Diseases: Has Peptidase Activity Only a Modulatory Role on the Interactions of PREP with Proteins?Frontiers in aging neuroscience · 2017Article
- Neuroinflammatory and autonomic mechanisms in diabetes and hypertension.American journal of physiology. Endocrinology and metabolism · 2016Review
- UCP2 Regulates Mitochondrial Fission and Ventromedial Nucleus Control of Glucose Responsiveness.Cell · 2016Article
- Hypothalamic-autonomic control of energy homeostasis.Endocrine · 2015Review
- The expression levels of prolyl oligopeptidase responds not only to neuroinflammation but also to systemic inflammation upon liver failure in rat models and cirrhotic patients.Journal of neuroinflammation · 2015Article
Corrections and comments
- Erratum issued
Authors and funding
14 authors at 5 institutions in 4 countries.
Funding
Abstract
Prolyl endopeptidase (PREP) has been implicated in neuronal functions. Here we report that hypothalamic PREP is predominantly expressed in the ventromedial nucleus (VMH), where it regulates glucose-induced neuronal activation. PREP knockdown mice (Prep(gt/gt)) exhibited glucose intolerance, decreased fasting insulin, increased fasting glucagon levels, and reduced glucose-induced insulin secretion compared with wild-type controls. Consistent with this, central infusion of a specific PREP inhibitor, S17092, impaired glucose tolerance and decreased insulin levels in wild-type mice. Arguing further for a central mode of action of PREP, isolated pancreatic islets showed no difference in glucose-induced insulin release between Prep(gt/gt) and wild-type mice. Furthermore, hyperinsulinemic euglycemic clamp studies showed no difference between Prep(gt/gt) and wild-type control mice. Central PREP regulation of insulin and glucagon secretion appears to be mediated by the autonomic nervous system because Prep(gt/gt) mice have elevated sympathetic outflow and norepinephrine levels in the pancreas, and propranolol treatment reversed glucose intolerance in these mice. Finally, re-expression of PREP by bilateral VMH injection of adeno-associated virus-PREP reversed the glucose-intolerant phenotype of the Prep(gt/gt) mice. Taken together, our results unmask a previously unknown player in central regulation of glucose metabolism and pancreatic function.
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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.