Journal of Neuroendocrinology最新文献

{"title":"Male rat hypothalamic extraretinal photoreceptor Opsin3 is sensitive to osmotic stimuli and light","authors":"Soledad Bárez-López,&nbsp;Paul Bishop,&nbsp;Daniel Searby,&nbsp;David Murphy,&nbsp;Michael P. Greenwood","doi":"10.1111/jne.13363","DOIUrl":"10.1111/jne.13363","url":null,"abstract":"<p>The light-sensitive protein Opsin 3 (Opn3) is present throughout the mammalian brain; however, the role of Opn3 in this organ remains unknown. Since <i>Opn3</i> encoded mRNA is modulated in the supraoptic and paraventricular nucleus of the hypothalamus in response to osmotic stimuli, we have explored by in situ hybridization the expression of <i>Opn3</i> in these nuclei. We have demonstrated that <i>Opn3</i> is present in the male rat magnocellular neurones expressing either the arginine vasopressin or oxytocin neuropeptides and that <i>Opn3</i> increases in both neuronal types in response to osmotic stimuli, suggesting that Opn3 functions in both cell types and that it might be involved in regulating water balance. Using rat hypothalamic organotypic cultures, we have demonstrated that the hypothalamus is sensitive to light and that the observed light sensitivity is mediated, at least in part, by Opn3. The data suggests that hypothalamic Opn3 can mediate a light-sensitive role to regulate circadian homeostatic processes.</p>","PeriodicalId":16535,"journal":{"name":"Journal of Neuroendocrinology","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jne.13363","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139403310","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of metformin on behavioral alterations produced by chronic sucrose consumption in male rats","authors":"Mariana Rey,&nbsp;Héctor Coirini,&nbsp;Agustina Marchena,&nbsp;María Claudia González Deniselle,&nbsp;María Sol Kruse","doi":"10.1111/jne.13362","DOIUrl":"10.1111/jne.13362","url":null,"abstract":"<p>Excessive consumption of sugary drinks negatively impacts the developing brain, producing long-lasting behavioral and metabolic disorders. Here, we study whether treatment with the antihyperglycemic agent metformin prevents some of the anxiety and memory alterations produced by chronic sucrose consumption. Male Sprague–Dawley rats had unrestricted access to water (control group) and a bottle containing a 10% sucrose solution (sucrose group, SUC) for 35 days. In parallel, a group of animals from SUC received metformin (25 mg/kg or 50 mg/kg, orally; MET 25 and MET 50 groups, respectively). After 2 weeks of metformin treatment, the animals weighed less than controls. SUC and MET 50 groups compensated for the caloric intake from the sugary solution by consuming less chow. In contrast, total energy intake in MET 25 was higher than the rest of the groups, but they still weighed less than control and SUC groups, suggesting that at this concentration, metformin delays body growth. The animals were then tested for the open field (OF), elevated plus maze (EPM) and novel object location (NOL) tests. In the OF, SUC animals spent more time in the central zone of the arena, evidenced by an increased number of entries and the distance traveled there. In the EPM, SUC animals spent more time in the open arms and less time in the central square. Metformin treatment prevented the decreased anxiety observed in SUC animals in the OF and EPM. In the NOL test, SUC animals showed less interest in novelty and metformin treatment did not improve this alteration. The preference for open spaces in the OF and EPM were associated with increased serum triglycerides (TG) and malondialdehyde levels in the medial prefrontal cortex (mPFC) and the hippocampus (HIP), while poor memory performance was associated with high basal blood glucose levels. In conclusion, the decreased anxiety-like behavior produced by chronic sucrose consumption was prevented by metformin treatment, through a mechanism that probably involves normalization of TG levels and decreased oxidative stress in mPFC and HIP.</p>","PeriodicalId":16535,"journal":{"name":"Journal of Neuroendocrinology","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2023-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139040126","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Use and perceived utility of [18F]FDG PET/CT in neuroendocrine neoplasms: A consensus report from the European Neuroendocrine Tumor Society (ENETS) Advisory Board Meeting 2022","authors":"Valentina Ambrosini,&nbsp;Martyn Caplin,&nbsp;Justo P. Castaño,&nbsp;Emanuel Christ,&nbsp;Timm Denecke,&nbsp;Christophe M. Deroose,&nbsp;Clarisse Dromain,&nbsp;Massimo Falconi,&nbsp;Simona Grozinsky-Glasberg,&nbsp;Rodney J. Hicks,&nbsp;Johannes Hofland,&nbsp;Andreas Kjaer,&nbsp;Ulrich Peter Knigge,&nbsp;Beata Kos-Kudla,&nbsp;Anna Koumarianou,&nbsp;Balkundi Krishna,&nbsp;Angela Lamarca,&nbsp;Marianne Pavel,&nbsp;Nicholas Simon Reed,&nbsp;Aldo Scarpa,&nbsp;Rajaventhan Srirajaskanthan,&nbsp;Anders Sundin,&nbsp;Christos Toumpanakis,&nbsp;Vikas Prasad","doi":"10.1111/jne.13359","DOIUrl":"10.1111/jne.13359","url":null,"abstract":"<p>Somatostatin receptor (SST) PET/CT is the gold standard for well-differentiated neuroendocrine tumours (NET) imaging. Higher grades of neuroendocrine neoplasms (NEN) show preferential [18F]FDG (FDG) uptake, and even low-grade NET may de-differentiate over time. FDG PET/CT's prognostic role is widely accepted; however, its impact on clinical decision-making remains controversial and its use varies widely. A questionnaire-based survey on FDG PET/CT use and perceived decision-making utility in NEN was submitted to the ENETS Advisory Board Meeting attendees (November 2022, response rate = 70%). In 3/15 statements, agreement was higher than 75%: (i) FDG was considered useful in NET, irrespective of grade, in case of mis-matched lesions (detectable on diagnostic CT but negative/faintly positive on SST PET/CT), especially if PRRT is contemplated (80%); (ii) in NET G3 if curative surgery is considered (82%); and (iii) in NEC prior to surgery with curative intent (98%). FDG use in NET G3, even in the presence of matched lesions, as a baseline for response assessment was favoured by 74%. Four statements obtained more than 60% consensus: (i) FDG use in NET G3 if locoregional therapy is considered (65%); (ii) in neuroendocrine carcinoma before initiating active therapy as a baseline for response assessment (61%); (iii) biopsy to re-assess tumour grade prior to a change in therapeutic management (68%) upon detection of FDG-positivity on the background of a prior G1-2 NET; (iv) 67% were in favour to reconsider PRRT to treat residual SST-positive lesions after achieving complete remission on FDG of the SST-negative disease component. Multidisciplinary opinion broadly supports the use of FDG PET/CT for characterisation of disease biology and to guide treatment selection across a range of indications, despite the lack of full consensus in many situations. This may reflect existing clinical access due to lack of reimbursement or experience with this investigation, which should be addressed by further research.</p>","PeriodicalId":16535,"journal":{"name":"Journal of Neuroendocrinology","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2023-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138684144","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction to “Efficacy, safety and unmet needs of evolving medical treatments for carcinoid syndrome”","authors":"","doi":"10.1111/jne.13361","DOIUrl":"10.1111/jne.13361","url":null,"abstract":"<p>\u0000 <span>Koumarianou, A</span>, <span>Daskalakis, K</span>, <span>Tsoli, M</span>, <span>Kaltsas, G</span>, <span>Pavel, M</span>. <span>Efficacy, safety and unmet needs of evolving medical treatments for carcinoid syndrome</span>. <i>J Neuroendocrinol.</i> <span>2022</span>; <span>34</span>(<span>7</span>):e13174. doi:10.1111/jne.13174\u0000 </p><p>An oversight has occurred in the published version of our paper “Efficacy, safety and unmet needs of evolving medical treatments for carcinoid syndrome”. Upon review, we have discovered in page 16, 1st line of paragraph 2.6 that we have defined and refer to the abbreviated term 5-HT as 5-hydroxytryptophane, whereas it should be 5-hydroxytryptamine, which is serotonin itself and not a precursor of the neurotransmitter.</p><p>We sincerely apologize for any confusion this may have caused.</p>","PeriodicalId":16535,"journal":{"name":"Journal of Neuroendocrinology","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2023-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jne.13361","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138684360","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical impact of unsuccessful subcutaneous administration of octreotide LAR instead of intramuscular administration in patients with metastatic gastroenteropancreatic neuroendocrine tumors","authors":"Tharani Krishnan,&nbsp;Maria Safro,&nbsp;Daniel Moreira Furlanetto,&nbsp;Sharlene Gill,&nbsp;Joao Paulo Solar Vasconcelos,&nbsp;Heather C. Stuart,&nbsp;Patrick Martineau,&nbsp;Jonathan M. Loree","doi":"10.1111/jne.13360","DOIUrl":"10.1111/jne.13360","url":null,"abstract":"<p>Octreotide LAR is a long-acting somatostatin analogue (SSA) used in the management of metastatic gastroenteropancreatic neuroendocrine tumors (GEP NETs). It requires intramuscular (IM) injection. Missed IM injections cause subcutaneous nodules (SCNs) on radiologic images. We reviewed the rates of SCNs in a real-world cohort of GEP NETs receiving octreotide LAR and explored treatment outcomes. Patients commencing octreotide LAR between August 5, 2010 and March 8, 2018 at a single cancer center in Canada were identified from pharmacy records. Patients were included if they had a computed tomography (CT) scan performed at the time of progression and a preceding CT with pelvis included to enable assessment for the presence of nodules. Fisher's exact test was used to examine predictors of SCNs, and Kaplan–Meier curves summarized differences in progression free (PFS) and overall survival (OS) that were compared with log-rank tests. Of 243 patients receiving octreotide LAR, 45 had all required CT images available for central review. SCNs were found in 20/45 (44%) of patients on the last scan showing stable disease before progression and were numerically but not statistically more likely in females (OR: 2.36, 95% CI: 0.66–8.29, <i>p</i> = .23). There was an increased risk of SCNs in patients with a skin-to-muscle distance &gt;38 mm (the length of an octreotide LAR needle) on CT (OR: 5.09, 95% CI: 1.39–16.6, <i>p</i> = .018) and a trend toward increased risk in obese patients (OR: 5.71, 95% CI: 1.26–23.4, <i>p</i> = .061). PFS (HR: 1.01, 95% CI: 0.56–1.78, <i>p</i> = .98) and OS (HR: 0.86, 95% CI: 0.41–1.8, <i>p</i> = .70) was similar between those with/without SCNs. In conclusion, almost half of patients receiving octreotide LAR had SCNs; however, missed administration of SSA did not appear to result in worse survival in this small study. Factors such as sex, younger age skin-to-muscle distance, and obesity may affect SCN development and should be considered when choosing an SSA.</p>","PeriodicalId":16535,"journal":{"name":"Journal of Neuroendocrinology","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2023-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jne.13360","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138684205","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Preconceptional and in utero exposure of sheep to a real-life environmental chemical mixture disrupts key markers of energy metabolism in male offspring","authors":"Mohammad Ghasemzadeh-Hasankolaei,&nbsp;Chris S. Elcombe,&nbsp;Samantha Powls,&nbsp;Richard G. Lea,&nbsp;Kevin D. Sinclair,&nbsp;Vasantha Padmanabhan,&nbsp;Neil P. Evans,&nbsp;Michelle Bellingham","doi":"10.1111/jne.13358","DOIUrl":"10.1111/jne.13358","url":null,"abstract":"<p>Over recent decades, an extensive array of anthropogenic chemicals have entered the environment and have been implicated in the increased incidence of an array of diseases, including metabolic syndrome. The ubiquitous presence of these environmental chemicals (ECs) necessitates the use of real-life exposure models to the assess cumulative risk burden to metabolic health. Sheep that graze on biosolids-treated pastures are exposed to a real-life mixture of ECs such as phthalates, per- and polyfluoroalkyl substances, heavy metals, pharmaceuticals, pesticides, and metabolites thereof, and this EC exposure can result in metabolic disorders in their offspring. Using this model, we evaluated the effects of gestational exposure to a complex EC mixture on plasma triglyceride (TG) concentrations and metabolic and epigenetic regulatory genes in tissues key to energy regulation and storage, including the hypothalamus, liver, and adipose depots of 11-month-old male offspring. Our results demonstrated a binary effect of EC exposure on gene expression particularly in the hypothalamus. Principal component analysis revealed two subsets (B-S1 [<i>n</i> = 6] and B-S2 [<i>n</i> = 4]) within the biosolids group (B, <i>n</i> = 10), relative to the controls (C, <i>n</i> = 11). Changes in body weight, TG levels, and in gene expression in the hypothalamus, and visceral and subcutaneous fat were apparent between biosolid and control and the two subgroups of biosolids animals. These findings demonstrate that gestational exposure to an EC mixture results in differential regulation of metabolic processes in adult male offspring. Binary effects on hypothalamic gene expression and altered expression of lipid metabolism genes in visceral and subcutaneous fat, coupled with phenotypic outcomes, point to differences in individual susceptibility to EC exposure that could predispose vulnerable individuals to later metabolic dysfunction.</p>","PeriodicalId":16535,"journal":{"name":"Journal of Neuroendocrinology","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2023-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jne.13358","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138684141","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dynamic, sex- and diet-specific pleiotropism in the PAC1 receptor-mediated regulation of arcuate proopiomelanocortin and Neuropeptide Y/Agouti related peptide neuronal excitability by anorexigenic ventromedial nucleus PACAP neurons","authors":"Veronica Mata-Pacheco,&nbsp;Jennifer Hernandez,&nbsp;Nandini Varma,&nbsp;Jenny Xu,&nbsp;Sarah Sayers,&nbsp;Nikki Le,&nbsp;Edward J. Wagner","doi":"10.1111/jne.13357","DOIUrl":"10.1111/jne.13357","url":null,"abstract":"<p>This study furthers the investigation of how pituitary adenylate cyclase activating polypeptide (PACAP) and the PAC1 receptor (PAC1R) regulate the homeostatic energy balance circuitry. We hypothesized that apoptotic ablation of PACAP neurones in the hypothalamic ventromedial nucleus (VMN) would affect both energy intake and energy expenditure. We also hypothesized that selective PAC1R knockdown would impair the PACAP-induced excitation in anorexigenic proopiomelanocortin (POMC) neurones and inhibition of orexigenic neuropeptide Y (NPY)/agouti-related peptide (AgRP) neurones in the hypothalamic arcuate nucleus (ARC). The results show CASPASE-3-induced ablation of VMN PACAP neurones leads to increased energy intake and meal frequency as well as decreased energy expenditure in lean animals. The effects were more robust in obese males, whereas we saw the opposite effects in obese females. We then utilized visualized whole-cell patch clamp recordings in hypothalamic slices. PAC1R knockdown in POMC neurones diminishes the PACAP-induced depolarization, increase in firing, decreases in energy intake and meal size, as well as increases in CO₂ production and O₂ consumption. Similarly, the lack of expression of the PAC1R in NPY/AgRP neurones greatly attenuates the PACAP-induced hyperpolarization, suppression of firing, decreases in energy intake and meal frequency, as well as increases in energy expenditure. The PACAP response in NPY/AgRP neurones switched from predominantly inhibitory to excitatory in fasted animals. Finally, the anorexigenic effect of PACAP was potentiated when oestradiol was injected into the ARC in ovariectomized females. This study demonstrates the critical role of anorexigenic VMN PACAP neurones and the PAC1R in exciting POMC and inhibiting NPY/AgRP neurons to control homeostatic feeding.</p>","PeriodicalId":16535,"journal":{"name":"Journal of Neuroendocrinology","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2023-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jne.13357","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138498652","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Peptide receptor chemoradionuclide therapy for neuroendocrine neoplasms: A systematic review.","authors":"Dennis S Chan, Aran L Kanagaratnam, Nick Pavlakis, David L Chan","doi":"10.1111/jne.13355","DOIUrl":"https://doi.org/10.1111/jne.13355","url":null,"abstract":"<p><p>Peptide receptor chemoradionuclide therapy (PRCRT), the addition of radiosensitising chemotherapy to peptide receptor radionuclide therapy (PRRT), has been used in individual centres for neuroendocrine neoplasms (NENs), but there are few data to date regarding its efficacy and safety. We conducted a systematic review to document the efficacy and side effect profile of this combination. We searched for studies including ≥5 patients with advanced NENs who received PRCRT. Major databases were searched and supplemented by handsearching of major conferences from 2019 to 2023. Data extracted included clinicopathological characteristics, trial setting and doses of chemotherapy and PRRT administered. Endpoints included overall survival (OS), progression-free survival (PFS) and adverse events (AEs); summarised qualitatively because of the marked heterogeneity in patient populations, trial designs and treatments administered. Eligible studies (24) included: 14 retrospective studies (643 patients) and 10 prospective studies (521 patients). For PRRT, most studies used ¹⁷⁷ Lu (n = 21), with combination ¹⁷⁷ Lu + ⁹⁰ Y (n = 2), ¹¹¹ In (n = 1) and ²²⁵ Ac (n = 1). Chemotherapy regimens included capecitabine (n = 8), capecitabine and temozolomide (n = 5), 5-fluorouracil (n = 4) or a mixture of regimens (n = 6). Most studies included Grade 1-2 NENs. In prospective studies, median OS exceeded 2 years in most studies (range not reached by end of follow-up-86 months). In retrospective studies, median OS ranged from 7 months to 55 months and was not reached in many studies. PFS data ranged from 31 months-not reached in prospective cohorts and from 4 months-not reached in retrospective cohorts. Grade 3/4 AEs were commonly haematological, with majority being reversible or having no ongoing clinical impact. For advanced NENs, PRCRT treatment has demonstrated promising clinical outcomes and was well tolerated, although identified studies were heterogeneous. Further randomised trial data are required to clarify the place of this combination modality in the NEN treatment paradigm.</p>","PeriodicalId":16535,"journal":{"name":"Journal of Neuroendocrinology","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2023-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138176452","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Alzheimer's disease-related brain insulin resistance and the prospective therapeutic impact of metformin","authors":"Hamed A. Abosharaf,&nbsp;Yasmin Elsonbaty,&nbsp;Ehab Tousson,&nbsp;Tarek M. Mohamed","doi":"10.1111/jne.13356","DOIUrl":"10.1111/jne.13356","url":null,"abstract":"<p>Besides COVID-19, two of the most critical outbreaks of our day are insulin resistance, type 2 diabetes mellitus (T2DM), and Alzheimer's disease (AD). Each disease's pathophysiology is well established. Furthermore, a substantial overlap between them has coexisted. Uncertainty remains on whether T2DM and AD are parallel illnesses with the same origin or separate illnesses linked through violent pathways. The current study was aimed at testing whether the insulin resistance in the brain results in AD symptoms or not. Insulin resistance was induced in the brains of rats using a single intracerebroventricular streptozotocin (STZ) dose. We then measured glucose, insulin receptor substrate 2 (IRS-2), amyloid β (Aβ) deposition, and tau phosphorylation in the brain to look for signs of insulin resistance and AD. The results of this study indicated that a single dose of STZ was able to induce insulin resistance in the brain and significantly decline IRS-2. This resistance was accompanied by obvious memory loss, Aβ deposition, and tau phosphorylation, further visible diminishing in neurotransmitters such as dopamine and acetylcholine. Furthermore, oxidative stress was increased due to the antioxidant system being compromised. Interestingly, the pancreas injury and peripheral insulin resistance coexisted with brain insulin resistance. Indeed, the antidiabetic metformin was able to enhance all these drastic effects. In conclusion, brain insulin resistance could lead to AD and vice versa. These are highly linked syndromes that could influence peripheral organs. Further studies are required to stabilize this putative pathobiology relationship between them.</p>","PeriodicalId":16535,"journal":{"name":"Journal of Neuroendocrinology","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2023-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138176451","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gene deletion of the PACAP/VIP receptor, VPAC2R, alters glycemic responses during metabolic and psychogenic stress in adult female mice","authors":"Elena V. Kozlova,&nbsp;Anthony E. Bishay,&nbsp;Maximilian E. Denys,&nbsp;Bhuvaneswari D. Chinthirla,&nbsp;Matthew C. Valdez,&nbsp;Kurt A. Spurgin,&nbsp;Julia M. Krum,&nbsp;Karthik R. Basappa,&nbsp;Margarita C. Currás-Collazo","doi":"10.1111/jne.13354","DOIUrl":"10.1111/jne.13354","url":null,"abstract":"<p>Pituitary adenylate cyclase-activating polypeptide (PACAP) and the homologous peptide, vasoactive intestinal peptide (VIP), participate in glucose homeostasis using insulinotropic and counterregulatory processes. The role of VIP receptor 2 (VPAC2R) in these opposing actions needs further characterization. In this study, we examined the participation of VPAC2R on basal glycemia, fasted levels of glucoregulatory hormones and on glycemia responses during metabolic and psychogenic stress using gene-deleted (<i>Vipr2</i>^{<i>−/−</i>}) female mice. The mean basal glycemia was significantly greater in <i>Vipr2</i>^{<i>−/−</i>} in the fed state and after an 8-h overnight fast as compared to wild-type (WT) mice. Insulin tolerance testing following a 5-h fast (morning fast, 0.38 U/kg insulin) indicated no effect of genotype. However, during a more intense metabolic challenge (8 h, ON fast, 0.25 U/kg insulin), <i>Vipr2</i>^{<i>−/−</i>} females displayed significantly impaired insulin hypoglycemia. During immobilization stress, the hyperglycemic response and plasma epinephrine levels were significantly elevated above basal in <i>Vipr2</i>^{<i>−/−</i>}, but not WT mice, in spite of similar stress levels of plasma corticosterone. Together, these results implicate participation of VPAC2R in upregulated counterregulatory processes influenced by enhanced sympathoexcitation. Moreover, the suppression of plasma GLP-1 levels in <i>Vipr2</i>^{<i>−/−</i>} mice may have removed the inhibition on hepatic glucose production and the promotion of glucose disposal by GLP-1. qPCR analysis indicated deregulation of central gene markers of PACAP/VIP signaling in <i>Vipr2</i>^{<i>−/−</i>}, upregulated medulla tyrosine hydroxylase (<i>Th</i>) and downregulated hypothalamic <i>Vip</i> transcripts. These results demonstrate a physiological role for VPAC2R in glucose metabolism, especially during insulin challenge and psychogenic stress, likely involving the participation of sympathoadrenal activity and/or metabolic hormones.</p>","PeriodicalId":16535,"journal":{"name":"Journal of Neuroendocrinology","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2023-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jne.13354","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"72014535","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}