International Journal of Endocrinology最新文献

{"title":"Effects of 18 Months of Growth Hormone Replacement Therapy on Bone Mineral Density in Patients with Adult Growth Hormone Deficiency: A Retrospective Study.","authors":"Ya-Yin Shen,&nbsp;Jia-Ni Ma,&nbsp;Zi-Yu Ren,&nbsp;Jie Liu,&nbsp;Xin-Yi Zhou,&nbsp;Xue-Rui Xie,&nbsp;Wei Ren","doi":"10.1155/2023/4988473","DOIUrl":"https://doi.org/10.1155/2023/4988473","url":null,"abstract":"<p><strong>Objective: </strong>The effect of physiological dose growth hormone (GH) replacement therapy on bone mineral density (BMD) in adults with growth hormone deficiency (GHD) is not well defined. We aimed to investigate the effects of 18 months of treatment with recombinant human growth hormone (rhGH) at physiological doses on BMD, body composition (BC), and quality of life (QoL).</p><p><strong>Methods: </strong>Sixty-eight patients diagnosed with adult growth hormone deficiency (AGHD) in our hospital were included in this retrospective study. All patients received individualized rhGH replacement to maintain normal serum insulin-like growth factor-1 (IGF-1) levels. BMD and BC measurements were performed by dual energy X-ray absorptiometry (DXA). Excluding those with incomplete follow-up data, we analyzed BMD in 68 patients, as well as BC and QoL in 36 of them.</p><p><strong>Results: </strong>Compared with the baseline, lumbar spine BMD decreased by 0.008 g/cm² (<i>P</i>=0.006) and increased by 0.011 g/cm² (<i>P</i>=0.045) at month 18, and total hip BMD decreased by 0.005 g/cm² (<i>P</i>=0.008) and did not change significantly from the baseline at month 18. The changes in BMD did not differ by sex, and the increase in BMD was more pronounced in patients with low <i>Z</i>-scores at the baseline (lumbar spine: <i>P</i>=0.005 and total hip: <i>P</i>=0.018). The percentage change from the baseline in BMD was greater for the lumbar spine than for the total hip (<i>P</i>=0.003). Lean body mass (LBM) increased significantly (<i>P</i>=0.012), total body fat ratio (TBF%) decreased significantly (<i>P</i>=0.011), visceral adipose tissue (VAT) decreased significantly (<i>P</i>=0.016), and QoL improved significantly (<i>P</i> < 0.001).</p><p><strong>Conclusions: </strong>Within 18 months of treatment, bone resorption manifested first, BMD decreased to a nadir at month 6, and then it increased. The increase in BMD was greater in the lumbar spine than in the hip, and the increase was more pronounced in patients with low BMD. Eighteen months of rhGH replacement therapy significantly improved lumbar spine BMD and improved BC and QoL.</p>","PeriodicalId":13966,"journal":{"name":"International Journal of Endocrinology","volume":"2023 ","pages":"4988473"},"PeriodicalIF":2.8,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10081901/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9282787","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":"Patients with Hypocortisolism Treated with Continuous Subcutaneous Hydrocortisone Infusion (CSHI): An Option for Poorly Controlled Patients.","authors":"Malene Lyder Mortensen,&nbsp;Marie Juul Ornstrup,&nbsp;Claus H Gravholt","doi":"10.1155/2023/5315059","DOIUrl":"https://doi.org/10.1155/2023/5315059","url":null,"abstract":"<p><strong>Objective: </strong>Despite appropriate oral glucocorticoid replacement therapy, patients with hypocortisolism often suffer from impaired health and frequent hospitalizations. Continuous subcutaneous hydrocortisone infusion (CSHI) has been developed as an attempt to improve the health status of these patients. The objective of this study was to compare the effects of CSHI to conventional oral treatment on hospitalizations, glucocorticoid doses, and subjective health status. <i>Patients</i>. Nine Danish patients (males: 4 and females: 5) with adrenal insufficiency (AI) were included, with a median age of 48 years, due to Addison (<i>n</i> = 4), congenital adrenal hyperplasia (<i>n</i> = 1), steroid induced secondary adrenal insufficiency (<i>n</i> = 2), morphine induced secondary adrenal insufficiency (<i>n</i> = 1), and Sheehan's syndrome (<i>n</i> = 1). Only patients with severe symptoms of cortisol deficit on oral treatment were selected for CSHI. Their usual oral hydrocortisone doses varied from 25-80 mg per day. The duration of follow-up depended on when the treatment was changed. The first patient started CSHI in 2009 and the last in 2021.</p><p><strong>Design: </strong>A retrospective case series comparing hospitalizations and glucocorticoid doses before and after treatment with CSHI. In addition, patients were retrospectively interviewed about their health-related quality of life (HRQoL) after the change of treatment modality.</p><p><strong>Results: </strong>Patients significantly reduced their daily dose of glucocorticoids by 16.1 mg (<i>p</i> = 0.02) after changing to CSHI. The number of hospital admission due to adrenal crisis decreased by 1.3 per year on CSHI, which was a 50% reduction (<i>p</i> = 0.04). All patients found it easier to handle an adrenal crisis with CSHI, and almost all patients found it easier to overcome everyday activities and had fewer symptoms of cortisol deficit such as abdominal pain and nausea (7-8 out of 9 patients).</p><p><strong>Conclusions: </strong>The change of treatment from conventional oral hydrocortisone to CSHI resulted in a reduced daily dose of glucocorticoids and a reduced number of hospitalizations. Patients reported regain of energy, achievement of better disease control, and better handling of adrenal crisis.</p>","PeriodicalId":13966,"journal":{"name":"International Journal of Endocrinology","volume":"2023 ","pages":"5315059"},"PeriodicalIF":2.8,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10042637/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9274692","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":"Expert Opinion on the Diagnosis and Management of Male Hypogonadism in India.","authors":"Sanjay Kalra,&nbsp;Jubbin Jacob,&nbsp;A G Unnikrishnan,&nbsp;Ganapathi Bantwal,&nbsp;Abhay Sahoo,&nbsp;Rakesh Sahay,&nbsp;Sushil Jindal,&nbsp;Madhu Sudan Agrawal,&nbsp;Nitin Kapoor,&nbsp;Banshi Saboo,&nbsp;Mangesh Tiwaskar,&nbsp;Kapil Kochhar","doi":"10.1155/2023/4408697","DOIUrl":"https://doi.org/10.1155/2023/4408697","url":null,"abstract":"<p><p>Male hypogonadism (MH) is a clinical and biochemical syndrome caused by inadequate synthesis of testosterone. Untreated MH can result in long-term effects, including metabolic, musculoskeletal, mood-related, and reproductive dysfunction. Among Indian men above 40 years of age, the prevalence of MH is 20%-29%. Among men with type 2 diabetes mellitus, 20.7% are found to have hypogonadism. However, due to suboptimal patient-physician communication, MH remains heavily underdiagnosed. For patients with confirmed hypogonadism (either primary or secondary testicular failure), testosterone replacement therapy (TRT) is recommended. Although various formulations exist, optimal TRT remains a considerable challenge as patients often need individually tailored therapeutic strategies. Other challenges include the absence of standardized guidelines on MH for the Indian population, inadequate physician education on MH diagnosis and referral to endocrinologists, and a lack of patient awareness of the long-term effects of MH in relation to comorbidities. Five nationwide advisory board meetings were convened to garner expert opinions on diagnosis, investigations, and available treatment options for MH, as well as the need for a person-centered approach. Experts' opinions have been formulated into a consensus document with the aim of improving the screening, diagnosis, and therapy of men living with hypogonadism.</p>","PeriodicalId":13966,"journal":{"name":"International Journal of Endocrinology","volume":"2023 ","pages":"4408697"},"PeriodicalIF":2.8,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9977550/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9101269","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":"CS27109, A Selective Thyroid Hormone Receptor-<i>β</i> Agonist Alleviates Metabolic-Associated Fatty Liver Disease in Murine Models.","authors":"Shengjian Huang,&nbsp;Zhou Deng,&nbsp;Wei Wang,&nbsp;Guoqiang Liao,&nbsp;Yiru Zhao,&nbsp;Hua Zhong,&nbsp;Qian Zhang,&nbsp;Jing Liu,&nbsp;Xuhua Mao,&nbsp;Beizhong Chen,&nbsp;Desi Pan,&nbsp;You Zhou","doi":"10.1155/2023/4950597","DOIUrl":"https://doi.org/10.1155/2023/4950597","url":null,"abstract":"<p><strong>Background/aim: </strong>Thyroid hormone receptor-<i>β</i> (THR-<i>β</i>) agonists play crucial roles in dyslipidemia and metabolic associated fatty liver disease (MAFLD). We developed a novel oral and liver-targeted THR-<i>β</i> agonist, CS27109, and evaluated its efficacy in the treatment of metabolic disorders.</p><p><strong>Materials and methods: </strong>We evaluated <i>in vitro</i> and <i>in vivo</i> efficacy and/or safety of CS27109 along with MGL3196 (a phase III THR-<i>β</i> agonist).</p><p><strong>Results: </strong>CS27109 showed pronounced activity and selectivity to THR-<i>β</i> and favorable PK properties, which was equivalent to MGL3196. In the hamster model, animals treated with a high dose of CS27109 showed equivalent reductions in serum TC and LDL-c with groups treated with MGL3196. In the rat model, CS27109 and MGL3196 reduced serum ALT, TC, TG, LDL-c, liver weight ratio, and liver steatosis. CS27109 simultaneously decreased liver TG and TC, and MGL3196 additionally reduced AST. In the mouse model, CS27109 dose-dependently reduced serum AST, ALT, liver inflammation, and NAS score, and also downregulated TC, LDL-c, liver steatosis, and fibrosis, but not in a dose-dependent manner. MGL3196 revealed an equivalent effect with CS27109 in that model. CS27109 also exhibited tolerable toxicity to the heart.</p><p><strong>Conclusions: </strong>CS27109 shows comparative <i>in vitro</i> and <i>in vivo</i> efficacy with MGL3196, suggesting its potential therapeutic application in the treatment of MAFLD such as dyslipidemia and steatohepatitis.</p>","PeriodicalId":13966,"journal":{"name":"International Journal of Endocrinology","volume":"2023 ","pages":"4950597"},"PeriodicalIF":2.8,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9943626/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10778829","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":"Research Progress on Mesenchymal Stem Cells for the Treatment of Diabetes and Its Complications.","authors":"Jiarui Zhang,&nbsp;Yongqin Zheng,&nbsp;Lichenlu Huang,&nbsp;Jundong He","doi":"10.1155/2023/9324270","DOIUrl":"https://doi.org/10.1155/2023/9324270","url":null,"abstract":"<p><p>Diabetes mellitus (DM) is a chronic disease that threatens human health. Although many drugs are available to treat DM, various complications caused by DM are unavoidable. As an emerging treatment for DM, mesenchymal stem cells (MSCs) have shown many advantages and are gradually gaining public attention. This review summarizes the clinical studies on the use of MSCs to treat DM and the potential mechanisms of complications such as pancreatic dysfunction, cardiovascular lesions, renal lesions, neurological lesions, and trauma repair. This review focuses on the research progress on MSC-mediated secretion of cytokines, improvements in the microenvironment, repair of tissue morphology, and related signaling pathways. At present, the sample sizes in clinical studies of MSCs in treating DM are small, and there is a lack of standardized quality control systems in the preparation, transportation, and infusion methods, so we need to conduct more in-depth studies. In conclusion, MSCs have shown superior potential for use in the treatment of DM and its complications and will hopefully become a novel therapeutic approach in the future.</p>","PeriodicalId":13966,"journal":{"name":"International Journal of Endocrinology","volume":"2023 ","pages":"9324270"},"PeriodicalIF":2.8,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10151724/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9784130","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":"Surgical Management of Giant Prolactinomas: A Descriptive Study.","authors":"Michelle D Lundholm,&nbsp;Divya Yogi-Morren,&nbsp;Kevin M Pantalone,&nbsp;Pablo F Recinos,&nbsp;Varun R Kshettry,&nbsp;Pratibha P R Rao","doi":"10.1155/2023/1990259","DOIUrl":"https://doi.org/10.1155/2023/1990259","url":null,"abstract":"<p><strong>Introduction: </strong>Giant prolactinoma (GP) is a rare pituitary lactotropic cell tumor larger than 4 cm in its widest dimension, and is less likely than a smaller prolactinoma to achieve prolactin normalization on dopamine agonist (DA) monotherapy. There is a paucity of data on the circumstances and outcomes of second-line management of GP with surgery. Herein, our institution's experience with the surgical management of GPs is described.</p><p><strong>Methods: </strong>A single-center retrospective analysis was conducted of patients who underwent surgery for giant prolactinoma from 2003 to 2018. A chart review was conducted for demographic data, clinical features, laboratory and radiographic findings, operative and pathology reports, perioperative management, and clinical outcomes in follow-up. Descriptive statistics were used.</p><p><strong>Results: </strong>Of 79 prolactinoma cases, 8 patients had GP with a median age of 38 years (range 20-53), 75% (6/8) were male, with a median largest tumor dimension of 6 cm (range 4.6-7.7), and a median prolactin level of 2,500 <i>μ</i>g/L (range 100->13,000). Six patients had transsphenoidal surgery for dopamine agonist (DA) resistance or intolerance. Two patients had a craniotomy for a missed diagnosis; one was due to the hook effect. No tumor resections were complete by either surgical approach; all had persistent hyperprolactinemia requiring postoperative DA therapy, and two patients had an additional craniotomy procedure for further tumor debulking. There was no recovery of pituitary axes and postoperative deficits were common. Remission as defined by prolactin normalization occurred in 63% (5/8) at a median time of 36 months (range 14-63 months) on DA therapy after surgery with a follow-up of 3-13 years.</p><p><strong>Conclusions: </strong>GPs infrequently require surgical resection, which is generally incomplete and requires adjuvant therapy. Given the rarity of surgery for GPs, multi-institutional or registry studies would yield clearer guidance on optimal management.</p>","PeriodicalId":13966,"journal":{"name":"International Journal of Endocrinology","volume":"2023 ","pages":"1990259"},"PeriodicalIF":2.8,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10154094/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9784131","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":"DHA Supplementation during Pregnancy in Women with Obesity Normalizes IGF2R Levels in the Placenta of Male Newborns.","authors":"Juan José Castro,&nbsp;Adriana Umana-Perez,&nbsp;Erika Castaño-Moreno,&nbsp;Paola Casanello,&nbsp;Ana María Ronco","doi":"10.1155/2023/1515033","DOIUrl":"https://doi.org/10.1155/2023/1515033","url":null,"abstract":"<p><strong>Introduction: </strong>Insulin-like growth factor receptor 2 (IGF2R) regulates placental nutrient transport, and its soluble form is related to obesity in adults. If the placental expression of IGF2R is altered in women with obesity is unknown. Whether maternal supplementation with docosahexaenoic acid (DHA), a polyunsaturated fatty acid with anti-inflammatory properties, has a modulatory role in IGF2R's function has not been elucidated. We hypothesized that maternal obesity (Ob) would be associated with alterations in placental IGF2R expression, which may be prevented with DHA supplementation during pregnancy.</p><p><strong>Methods: </strong>At delivery, we obtained placentas from women with Ob (BMI ≥ 30 kg/m², <i>n</i> = 17), Ob supplemented with 800 mg/day of DHA during pregnancy (Ob + DHA, <i>n</i> = 13), and normal-weight women (Nw, BMI ≥ 18.5 ≤ 24.9 kg/m², <i>n</i> = 14). The IGF2R mRNA and protein were determined by RT-PCR and western blotting, respectively. Moreover, we quantified the gene expression of molecules that modulate the IGF2R function in the extracellular domain, such as TACE/ADAM17, PLAU, and IGF2. Mann-Whitney and Kruskal-Wallis nonparametric tests were used to compare results between two or three groups accordingly.</p><p><strong>Results: </strong>The IGF2R levels in the Ob placentas of the male offspring were higher than in the Nw group. The DHA supplementation prevented this effect, suggesting an unknown relationship between IGF2R-Ob-DHA in placental tissues.</p><p><strong>Conclusion: </strong>We report, for the first time, that DHA supplementation during pregnancy in women with obesity normalizes the increased IGF2R levels in male placentas, reducing the risk of adverse outcomes related to the IGF2/IGF2R system in male newborns.</p>","PeriodicalId":13966,"journal":{"name":"International Journal of Endocrinology","volume":"2023 ","pages":"1515033"},"PeriodicalIF":2.8,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10319466/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9803888","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":"Identification of Risk Factors and Development of a Predictive Model for Postoperative Hypoglycemia among Diabetic Patients during the Perioperative Period.","authors":"Zixuan Liu,&nbsp;Jing Dai,&nbsp;Xiaodie He,&nbsp;Jiaxi Li,&nbsp;Haixia Zhang,&nbsp;Cheng Ji","doi":"10.1155/2023/8033101","DOIUrl":"https://doi.org/10.1155/2023/8033101","url":null,"abstract":"<p><strong>Objective: </strong>To explore the incidence and influencing factors of postoperative hypoglycemia in diabetic patients during the perioperative period and to construct a risk prediction model for postoperative hypoglycemia.</p><p><strong>Methods: </strong>Patients with T2DM admitted to the nonendocrinology department of Nanjing Drum Tower Hospital from December 2019 to January 2022 were included as research subjects. Basic information, hospital blood glucose management methods, laboratory indicators, and surgery-related indicators were collected. A risk prediction model and scoring table for postoperative hypoglycemia in patients with perioperative diabetes mellitus were established.</p><p><strong>Results: </strong>A total of 440 patients were included, of which 109 had hypoglycemia, resulting in an incidence of postoperative hypoglycemia of 24.78%. The results show that preoperative C-peptide and operation duration were risk factors for postoperative hypoglycemia, while BMI and preoperative fasting blood glucose were protective factors.</p><p><strong>Conclusion: </strong>The model constructed in this study is a good method for evaluating the risk of postoperative hypoglycemia. The scoring table intuitively quantifies the risk of risk factors for outcome variables and has strong clinical practicability.</p>","PeriodicalId":13966,"journal":{"name":"International Journal of Endocrinology","volume":"2023 ","pages":"8033101"},"PeriodicalIF":2.8,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10480020/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10533781","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":"PNPLA3 148M/M Is More Susceptible to Palmitic Acid-Induced Endoplasmic Reticulum Stress-Associated Apoptosis in HepG2 Cells.","authors":"Yunzhi Chen,&nbsp;Xuemei Yan,&nbsp;Tian Wang,&nbsp;Hongrong Deng,&nbsp;Xiaojie Deng,&nbsp;Fen Xu,&nbsp;Hua Liang","doi":"10.1155/2023/2872408","DOIUrl":"https://doi.org/10.1155/2023/2872408","url":null,"abstract":"<p><strong>Background: </strong>Patatin-like phospholipase domain-containing 3 (PNPLA3) is a major susceptibility gene for nonalcoholic fatty liver disease (NAFLD), and its rs738409 (I148M) polymorphism is associated with the occurrence and progression of NAFLD. Endoplasmic reticulum (ER) stress-related hepatocyte lipoapoptosis contributes to the progress of NAFLD. PNPLA3 is also known as a member of the calcium-independent phospholipase A2<i>ε</i> family, which can hydrolyze fatty acids to generate lysophosphatidylcholine (LPC) that induces ER stress-related hepatocyte lipoapoptosis. Whether the PNPLA3 risk genotype 148M/M is involved in more severe ER stress-associated lipoapoptosis is unclear.</p><p><strong>Methods: </strong>A PNPLA3148I knock-in HepG2 cell model was constructed based on HepG2 expressing PNPLA3 148M/M using the Cas9/sgRNA system. PNPLA3 148M/M, I/M, and I/I cells were treated with 0.3 mM palmitic acid (PA) for 24 h to induce lipid deposition. Cellular lipid deposition was detected by oil red staining. Apoptosis was observed by TUNEL. LPC was determined by ELISA, and the expression of PNPLA3, the ER stress marker Bip, molecules involved in the ER stress PERK/elF-2a pathway, and its downstream C/EBP homologous protein (CHOP)-mediated apoptotic pathway were detected by western blot.</p><p><strong>Results: </strong>The results showed no difference in PNPLA3 basal expression and basal hepatocyte lipid content between the three genotypes of cells. Lipid deposition and apoptosis were more severe in PNPLA3 148M/M and 148I/M cells than in I/I cells after PA treatment. PA-induced upregulation of protein expression of Bip, ER stress-responsive PERK pathway molecules p-PERK, p-eIF2<i>α</i>, CHOP, and CHOP-associated apoptotic molecules PUMA and Bax were more pronounced in PNPLA3 148M/M cells than in PNPLA3 148I/I cells. The basal LPC levels and the PA-treated increase of LPC levels in the cell culture supernatants did not differ between the three genotypic cells.</p><p><strong>Conclusion: </strong>PNPLA3 148M/M cells were more susceptible to PA-induced lipid deposition and ER stress-related apoptosis than 148I/I cells, and the proapoptotic susceptibility of PNPLA3 148M/M is independent of LPC.</p>","PeriodicalId":13966,"journal":{"name":"International Journal of Endocrinology","volume":"2023 ","pages":"2872408"},"PeriodicalIF":2.8,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9943609/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10770008","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":"Dulaglutide Protects Mice against Diabetic Sarcopenia-Mediated Muscle Injury by Inhibiting Inflammation and Regulating the Differentiation of Myoblasts.","authors":"Fengyi Deng,&nbsp;Wenyan Wu,&nbsp;Xingyu Fan,&nbsp;Xing Zhong,&nbsp;Nuojin Wang,&nbsp;Yue Wang,&nbsp;Tianrong Pan,&nbsp;Yijun Du","doi":"10.1155/2023/9926462","DOIUrl":"https://doi.org/10.1155/2023/9926462","url":null,"abstract":"<p><strong>Background: </strong>Type 2 diabetes mellitus increases the risk of sarcopenia, which is characterized by decreased muscle mass, strength, and function. However, there are no effective drugs to treat diabetic sarcopenia, and its underlying mechanism remains unknown. Here, we aimed to determine whether the GLP-1 receptor agonist (GLP-1RA) dulaglutide (Dul) affects the progression of diabetic sarcopenia.</p><p><strong>Methods: </strong>db/db mice were injected intraperitoneally with 0.6 mg/kg dulaglutide for 10 weeks. Mouse muscle tissues were then pathologically evaluated and stained with F4/80 or MPO to detect macrophages and neutrophils, respectively. In addition, inflammatory factors and FNDC5 in the muscle tissues were detected using qRT-PCR. Moreover, C2C12 cells were induced to enable their differentiation into skeletal muscle cells, and muscle factor levels were then detected. Furthermore, changes in muscle factor levels were detected at various glucose concentrations (11 mM, 22 mM, and 44 mM).</p><p><strong>Results: </strong>In vivo, dulaglutide alleviated muscle tissue injury; reduced levels of the inflammatory factors, IL-1<i>β</i>, IL-6, CCL2, and CXCL1; and reversed the level of FNDC5 in the muscle tissues of db/db mice. In vitro, a C2C12 cell differentiation model was established through the observation of cell morphology and determination of myokine levels. Upon stimulation with high glucose, the differentiation of C2C12 cells was inhibited. Dulaglutide improved this inhibitory state by upregulating the levels of both FNDC5 mRNA and protein.</p><p><strong>Conclusions: </strong>Treatment with the GLP-1RA dulaglutide protects db/db mice against skeletal muscle injury by inhibiting inflammation and regulating the differentiation of myoblasts. High glucose inhibited the differentiation of C2C12 cells and decreased the mRNA and protein levels of myokines. Dulaglutide could reverse the differentiation state induced in C2C12 cells by high glucose.</p>","PeriodicalId":13966,"journal":{"name":"International Journal of Endocrinology","volume":"2023 ","pages":"9926462"},"PeriodicalIF":2.8,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10425251/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10013199","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}