Journal of Endocrinology最新文献

Deletion of GFRAL blunts weight lowering effects of FGF21 in female mice.

IF 3.4 3区医学

Journal of Endocrinology Pub Date : 2025-04-01 DOI: 10.1530/JOE-25-0017

Alberte Silke Buch-Rasmussen, Helle Andersen, Christina Stage, Ann Maria Kruse Hansen, Sarah Juel Paulsen, Matthew Paul Gillum, Birgitte Andersen, Anna Secher, Markus Latta, Christoffer Clemmensen, Sebastian Jorgensen

{"title":"Deletion of GFRAL blunts weight lowering effects of FGF21 in female mice.","authors":"Alberte Silke Buch-Rasmussen, Helle Andersen, Christina Stage, Ann Maria Kruse Hansen, Sarah Juel Paulsen, Matthew Paul Gillum, Birgitte Andersen, Anna Secher, Markus Latta, Christoffer Clemmensen, Sebastian Jorgensen","doi":"10.1530/JOE-25-0017","DOIUrl":"10.1530/JOE-25-0017","url":null,"abstract":"The role of the GDF15 receptor, GDNF family receptor alpha like (GFRAL), in the metabolic effects of FGF21 was investigated by treating female GFRAL knockout mice with recombinant human FGF21. In contrast to FGF21-treated wildtype mice, which lost 12% body weight relative to vehicle, the absence of GFRAL coincided with a greater compensatory increase in food intake, and accordingly, the weight-lowering effect of FGF21 treatment was blunted. Interestingly, the glycaemic benefits of FGF21 persisted in the absence of GFRAL. Potential crosstalk between FGF21 and GDF15 was further investigated acutely in obese male rats in which a single dose of FGF21 did not increase endogenous circulating GDF15 levels and vice versa. Lastly, overexpression of GDF15 or FGF21 with hydrodynamic gene delivery in obese male mice did not alter the expression of the other's receptor complex in regions of the hypothalamus and hindbrain. Collectively, we demonstrate an impaired weight lowering effect of exogenous FGF21 in female GFRAL knockout mice. Yet, the further examination of the interconnectedness between GDF15 and FGF21 endocrine axes in male rodents imply that they largely operate in parallel and are not extensively intertwined. In future studies, it will be important to investigate the influence of sex, particularly on the role of GDF15-GFRAL signalling in regulating compensatory food intake induced by FGF21 pharmacology.","PeriodicalId":15740,"journal":{"name":"Journal of Endocrinology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143752927","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Cold aerobic exercise mitigates NAFLD fibrosis through UBAP2L-regulated TGFβ/Smad2 signaling.

IF 3.4 3区医学

Journal of Endocrinology Pub Date : 2025-03-01 DOI: 10.1530/JOE-24-0351

Jianhong Zhang, Chaoyang Li, Zhijian Rao, Xue Geng, Chen Liang, Shijie Liu, Peng Huang, Dongzhe Wu, Yiwei Feng, Jiexiu Zhao

{"title":"Cold aerobic exercise mitigates NAFLD fibrosis through UBAP2L-regulated TGFβ/Smad2 signaling.","authors":"Jianhong Zhang, Chaoyang Li, Zhijian Rao, Xue Geng, Chen Liang, Shijie Liu, Peng Huang, Dongzhe Wu, Yiwei Feng, Jiexiu Zhao","doi":"10.1530/JOE-24-0351","DOIUrl":"10.1530/JOE-24-0351","url":null,"abstract":"Non-alcoholic fatty liver disease (NAFLD) can progress to fibrosis and hepatocellular carcinoma, with TGFβ playing a key role. UBAP2L regulates TGFβ expression, but its role in NAFLD remains unclear. While exercise improves NAFLD and cold exposure enhances lipid metabolism, their combined effects on NAFLD-induced fibrosis are unknown. This study examines whether exercise with cold exposure (ECE) attenuates NAFLD-induced fibrosis via UBAP2L-mediated TGFβ/Smad2/3 pathway. Fifty 5-week-old male C57BL/6N mice were assigned to five groups: normal control (C), high-fat diet (H), high-fat diet with cold exposure (HC), high-fat diet with exercise (HE), and high-fat diet with ECE (HCE). After 8 weeks of high-fat diet feeding, the HE and HCE groups underwent treadmill exercise (50 minutes/session, 5 days/week for 8 weeks). HE, Oil Red O, Masson staining, biochemical analyses, proteomics, WB, and RT-qPCR were used to assess fibrosis-related markers. We found that body weight, liver weight, hepatic TG, TC, LDL, Glu, CHO, and AST, ALT were significantly elevated in H group. In HCE group, hepatic TG and BUN decreased, while HDL increased. Proteomics identified UBAP2L as the most upregulated protein in H group, but it was downregulated in HCE group. WB confirmed UBAP2L overexpression in H group and its reduction in HCE group, with decreased α-SMA. RT-qPCR showed elevated TGFβ, α-SMA, Smad2, Smad3, Col1a2 and UBAP2L in H group, which were downregulated by ECE. ECE reduces NAFLD-induced hepatic fibrosis, probably by downregulating UBAP2L and suppressing TGFβ/Smad2 pathway. These suggest ECE may be more effective than exercise at normal temperatures in Mitigating NAFLD-related fibrosis.","PeriodicalId":15740,"journal":{"name":"Journal of Endocrinology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143752904","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Leptin potentiates bone loss at skeletal sites distant from focal inflammation in female ob/ob mice.

IF 3.4 3区医学

Journal of Endocrinology Pub Date : 2025-02-17 Print Date: 2025-03-01 DOI: 10.1530/JOE-24-0324

Russell T Turner, Kenneth A Philbrick, Carmen P Wong, Aidan R Fichter, Adam J Branscum, Urszula T Iwaniec

{"title":"Leptin potentiates bone loss at skeletal sites distant from focal inflammation in female ob/ob mice.","authors":"Russell T Turner, Kenneth A Philbrick, Carmen P Wong, Aidan R Fichter, Adam J Branscum, Urszula T Iwaniec","doi":"10.1530/JOE-24-0324","DOIUrl":"10.1530/JOE-24-0324","url":null,"abstract":"Leptin increases focal inflammation and osteolysis induced by polyethylene particles in leptin-deficient ob/ob mice, suggesting that this adipokine, an important immune modulator, contributes to orthopedic implant failure. Focal inflammation leads to bone loss at distant skeletal sites, and it is plausible that leptin also contributes to this response. We tested this possibility in 6-week-old female ob/ob mice (6-8/group) by evaluating bone architecture, turnover and gene expression 12 days following the surgical placement of polyethylene particles over the calvaria. Particle treatment had minimal effect on bone mass, density or cancellous bone architecture in the femur and 5th lumbar vertebra (LV). However, compared to controls, particle treatment altered tibial expression levels of 32/84 genes related to bone metabolism. Subcutaneous infusion of leptin (6 μg/d) to mice following the placement of polyethylene particles over the calvaria (combination treatment) resulted in cancellous bone loss in the distal femur metaphysis and LV and in the differential expression of 34/84 genes, 15 of which overlapped with particle treatment. Notably, combination treatment, but not particle treatment, resulted in increased expression of genes strongly associated with bone turnover and response to inflammation. Leptin treatment alone (0.1-10 μg/day) did not result in bone loss in the femur or LV in the ob/ob mice. These findings suggest that leptin exaggerates the detrimental effects of particle-induced inflammation on bone turnover balance, leading to systemic bone loss.","PeriodicalId":15740,"journal":{"name":"Journal of Endocrinology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11960745/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143066138","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Steroidogenic acute regulatory protein in fish.

IF 3.4 3区医学

Journal of Endocrinology Pub Date : 2025-02-17 Print Date: 2025-04-01 DOI: 10.1530/JOE-24-0232

Jannet Kocerha, Nancy D Denslow

引用次数: 0

GLP-1R/NPY2R regulate gene expression, ovarian and adrenal morphology in HFD mice. GLP-1R/NPY2R调节HFD小鼠的基因表达、卵巢和肾上腺形态。

IF 3.4 3区医学

Journal of Endocrinology Pub Date : 2025-01-10 Print Date: 2025-02-01 DOI: 10.1530/JOE-24-0189

Dawood Khan, Ananyaa Sridhar, Charlotte R Moffett

{"title":"GLP-1R/NPY2R regulate gene expression, ovarian and adrenal morphology in HFD mice.","authors":"Dawood Khan, Ananyaa Sridhar, Charlotte R Moffett","doi":"10.1530/JOE-24-0189","DOIUrl":"10.1530/JOE-24-0189","url":null,"abstract":"Glucagon-like peptide-1 receptor (GLP-1R) and neuropeptide Y receptors (NPYRs) are expressed in reproductive tissues contributing to the regulation of gonadal function. This exploratory study examines the potential impact of their modulation by assessing the effects of exendin-4 (Ex-4) and peptide YY (PYY) (3-36) on endocrine ovaries and adrenals in high-fat diet (HFD) mice. Ex-4 and PYY(3-36) reduced blood glucose and energy intake, with no effects on body weight. While HFD did not impact the estrous cycle, Ex-4 increased metestrus frequency and decreased diestrus frequency resulting in 0% mice experiencing repeated diestrus or becoming acyclic. Luteinizing hormone levels were significantly higher in the Ex-4 and PYY(3-36) groups compared to the normal diet and HFD controls. In the adrenals, reduced capsule and zona glomerulosa thickness caused by HFD was reversed after peptide treatments. Within the ovaries, HFD increased the number of atretic follicles, an effect that disappeared after Ex-4 and PYY(3-36) treatments. Ex-4 also increased the number of corpora lutea owing to the prolonged metestrus phase. Gene expression analysis within the adrenals revealed the upregulation of Insr and the downregulation of Prgtr in HFD mice, while Ex-4 downregulated the expression of Gipr. The ovarian gene expression of Gipr, Npy1r and Prgtr was downregulated by Ex-4 treatment, while PYY(3-36) significantly downregulated the Prgtr expression compared to HFD mice. These data indicate that manipulating GLP-1R and NPY2R leads to changes in the reproductive physiology of mice. In addition, the observed alterations in the morphology and gene expression in the adrenals and ovaries imply a direct impact of these peptides on female reproductive function.","PeriodicalId":15740,"journal":{"name":"Journal of Endocrinology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11798413/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142846681","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Continuing the success of Journal of Endocrinology and Journal of Molecular Endocrinology: Editor-in-Chief handover. 延续《内分泌学杂志》和《分子内分泌学杂志》的成功：主编交接。

IF 3.4 3区医学

Journal of Endocrinology Pub Date : 2024-12-18 Print Date: 2025-01-01 DOI: 10.1530/JOE-24-0305

Martin Haluzik, Gabriela da Silva Xavier

引用次数: 0

Glucocorticoid excess alters metabolic rate and substrate utilisation via 11β-HSD1. 糖皮质激素过量会通过 11β-HSD1 改变代谢率和底物利用率。

IF 3.4 3区医学

Journal of Endocrinology Pub Date : 2024-10-28 Print Date: 2024-11-01 DOI: 10.1530/JOE-24-0205

Samuel R Heaselgrave, Silke Heising, Stuart A Morgan, David M Carthwright, Michael Sagmeister, Rowan S Hardy, Craig L Doig, Nicholas Morton, Kostas Tsintzas, Gareth G Lavery

{"title":"Glucocorticoid excess alters metabolic rate and substrate utilisation via 11β-HSD1.","authors":"Samuel R Heaselgrave, Silke Heising, Stuart A Morgan, David M Carthwright, Michael Sagmeister, Rowan S Hardy, Craig L Doig, Nicholas Morton, Kostas Tsintzas, Gareth G Lavery","doi":"10.1530/JOE-24-0205","DOIUrl":"10.1530/JOE-24-0205","url":null,"abstract":"Systemic glucocorticoid excess causes several adverse metabolic conditions, most notably Cushing's syndrome. These effects are amplified by the intracellular enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1). Here, we determined the less well-characterised effects of glucocorticoid excess, and the contribution of 11β-HSD1 amplification on metabolic rate in mice. Male and female C57BL/6J (wild type, WT) and 11β-HSD1 knockout (11β-HSD1 KO) mice were treated with high-dose corticosterone or a vehicle control for 3 weeks. Indirect calorimetry was conducted during the final week of treatment, with or without fasting, to determine the impact on metabolic rate. We found that corticosterone treatment elevated metabolic rate and promoted carbohydrate utilisation primarily in female WT mice, with effects more pronounced during the light phase. Corticosterone treatment also resulted in greater fat accumulation in female WT mice. Corticosterone induced hyperphagia was identified as a likely causal factor altering the respiratory exchange ratio (RER) but not energy expenditure (EE). Male and female 11β-HSD1 KO mice were protected against these effects. We identify novel metabolic consequences of sustained glucocorticoid excess, identify a key mechanism of hyperphagia, and demonstrate that 11β-HSD1 is required to manifest the full metabolic derangement.","PeriodicalId":15740,"journal":{"name":"Journal of Endocrinology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11558800/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142288974","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

GLP-1 receptor agonist-based therapies and cardiovascular risk: a review of mechanisms. GLP-1 受体激动剂与心血管风险：机制综述。

IF 3.4 3区医学

Journal of Endocrinology Pub Date : 2024-09-19 Print Date: 2024-10-01 DOI: 10.1530/JOE-24-0046

Neerav Mullur, Arianne Morissette, Nadya M Morrow, Erin E Mulvihill

{"title":"GLP-1 receptor agonist-based therapies and cardiovascular risk: a review of mechanisms.","authors":"Neerav Mullur, Arianne Morissette, Nadya M Morrow, Erin E Mulvihill","doi":"10.1530/JOE-24-0046","DOIUrl":"10.1530/JOE-24-0046","url":null,"abstract":"Cardiovascular outcome trials (CVOTs) in people living with type 2 diabetes mellitus and obesity have confirmed the cardiovascular benefits of glucagon-like peptide 1 receptor agonists (GLP-1RAs), including reduced cardiovascular mortality, lower rates of myocardial infarction, and lower rates of stroke. The cardiovascular benefits observed following GLP-1RA treatment could be secondary to improvements in glycemia, blood pressure, postprandial lipidemia, and inflammation. Yet, the GLP-1R is also expressed in the heart and vasculature, suggesting that GLP-1R agonism may impact the cardiovascular system. The emergence of GLP-1RAs combined with glucose-dependent insulinotropic polypeptide and glucagon receptor agonists has shown promising results as new weight loss medications. Dual-agonist and tri-agonist therapies have demonstrated superior outcomes in weight loss, lowered blood sugar and lipid levels, restoration of tissue function, and enhancement of overall substrate metabolism compared to using GLP-1R agonists alone. However, the precise mechanisms underlying their cardiovascular benefits remain to be fully elucidated. This review aims to summarize the findings from CVOTs of GLP-1RAs, explore the latest data on dual and tri-agonist therapies, and delve into potential mechanisms contributing to their cardioprotective effects. It also addresses current gaps in understanding and areas for further research.","PeriodicalId":15740,"journal":{"name":"Journal of Endocrinology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11466209/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141982464","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Aldosterone, mitochondria and regulation of cardiovascular metabolic disease. 醛固酮、线粒体和心血管代谢疾病的调节。

IF 3.4 3区医学

Journal of Endocrinology Pub Date : 2024-09-13 Print Date: 2024-10-01 DOI: 10.1530/JOE-23-0350

Cheng-Hsuan Tsai, Zheng-Wei Chen, Bo-Ching Lee, Che-Wei Liao, Yi-Yao Chang, Yan-Rou Tsai, Chia-Hung Chou, Vin-Cent Wu, Chi-Sheng Hung, Yen-Hung Lin

{"title":"Aldosterone, mitochondria and regulation of cardiovascular metabolic disease.","authors":"Cheng-Hsuan Tsai, Zheng-Wei Chen, Bo-Ching Lee, Che-Wei Liao, Yi-Yao Chang, Yan-Rou Tsai, Chia-Hung Chou, Vin-Cent Wu, Chi-Sheng Hung, Yen-Hung Lin","doi":"10.1530/JOE-23-0350","DOIUrl":"10.1530/JOE-23-0350","url":null,"abstract":"Aldosterone is a mineralocorticoid hormone involved in controlling electrolyte balance, blood pressure, and cellular signaling. It plays a pivotal role in cardiovascular and metabolic physiology. Excess aldosterone activates mineralocorticoid receptors, leading to subsequent inflammatory responses, increased oxidative stress, and tissue remodeling. Various mechanisms have been reported to link aldosterone with cardiovascular and metabolic diseases. However, mitochondria, responsible for energy generation through oxidative phosphorylation, have received less attention regarding their potential role in aldosterone-related pathogenesis. Excess aldosterone leads to mitochondrial dysfunction, and this may play a role in the development of cardiovascular and metabolic diseases. Aldosterone has the potential to affect mitochondrial structure, function, and dynamic processes, such as mitochondrial fusion and fission. In addition, aldosterone has been associated with the suppression of mitochondrial DNA, mitochondria-specific proteins, and ATP production in the myocardium through mineralocorticoid receptor, nicotinamide adenine dinucleotide phosphate oxidase, and reactive oxygen species pathways. In this review, we explore the mechanisms underlying aldosterone-induced cardiovascular and metabolic mitochondrial dysfunction, including mineralocorticoid receptor activation and subsequent inflammatory responses, as well as increased oxidative stress. Furthermore, we review potential therapeutic targets aimed at restoring mitochondrial function in the context of aldosterone-associated pathologies. Understanding these mechanisms is vital, as it offers insights into novel therapeutic strategies to mitigate the impact of aldosterone-induced mitochondrial dysfunction, thereby potentially improving the outcomes of individuals affected by cardiovascular and metabolic disorders.","PeriodicalId":15740,"journal":{"name":"Journal of Endocrinology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141909808","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The GHSR1a antagonist LEAP2 regulates islet hormone release in a sex-specific manner GHSR1a 拮抗剂 LEAP2 以性别特异性方式调节胰岛激素的释放

IF 4 3区医学

Journal of Endocrinology Pub Date : 2024-09-01 DOI: 10.1530/joe-24-0135

Nirun Hewawasam, Debalina Sakar, Olivia Bolton, Blerinda Delishaj, Maha Almutairi, Aileen King, Ayse S Dereli, Chloe Despontin, Patrick Gilon, Sue Reeves, Michael Patterson, Astrid Christine Hauge-Evans

{"title":"The GHSR1a antagonist LEAP2 regulates islet hormone release in a sex-specific manner","authors":"Nirun Hewawasam, Debalina Sakar, Olivia Bolton, Blerinda Delishaj, Maha Almutairi, Aileen King, Ayse S Dereli, Chloe Despontin, Patrick Gilon, Sue Reeves, Michael Patterson, Astrid Christine Hauge-Evans","doi":"10.1530/joe-24-0135","DOIUrl":"https://doi.org/10.1530/joe-24-0135","url":null,"abstract":"LEAP2, a liver-derived antagonist for the ghrelin receptor, GHSR1a, counteracts effects of ghrelin on appetite and energy balance. Less is known about its impact on blood glucose-regulating hormones from pancreatic islets. Here we investigate whether acyl-ghrelin (AG) and LEAP2 regulate islet hormone release in a cell type- and sex-specific manner. Hormone content from secretion experiments with isolated islets from male and female mice was measured by radioimmunoassay and mRNA expression by qPCR. LEAP2 enhanced insulin secretion in islets from males (p<0.01) but not females (p<0.2), whilst AG-stimulated somatostatin release was significantly reversed by LEAP2 in males (p<0.001) but not females (p<0.2). Glucagon release was not significantly affected by AG and LEAP2. Ghsr1a, Ghrelin, Leap2, Mrap2, Mboat4 and Sstr3 islet mRNA expression did not differ between sexes. In control male islets maintained without 17-beta oestradiol (E2), AG exerted an insulinostatic effect (p<0.05), with a trend towards reversal by LEAP2 (p=0.06). Both were abolished by 72h E2 pre-treatment (10 nmol/l, p<0.2). AG-stimulated somatostatin release was inhibited by LEAP2 from control (p<0.001) but not E2-treated islets (p<0.2). LEAP2 and AG did not modulate insulin secretion from MIN6 beta cells and Mrap2 was downregulated (P<0.05) and Ghsr1a upregulated (P<0.0001) in islets from Sst-/-\u0000 mice. Our findings show that AG and LEAP2 regulate insulin and somatostatin release in an opposing and sex-dependent manner, which in males can be modulated by E2. We suggest that regulation of SST release is a key starting point for understanding the role of GHSR1a in islet function and glucose metabolism.","PeriodicalId":15740,"journal":{"name":"Journal of Endocrinology","volume":"31 1","pages":""},"PeriodicalIF":4.0,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142255678","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0