Pub Date : 2024-05-09DOI: 10.3390/endocrines5020015
Chrysoula Kosmeri, Maria S Baltogianni, V. Giapros, E. Siomou, V. Tsinopoulou, Foteini Balomenou, Anastasios Serbis
Basal insulin analogs, typically administered once or twice daily, have been one of the two pillars of the multiple daily injection (MDI) insulin therapy of patients with type 1 diabetes (T1D) for the last twenty years. Recently, once-weekly basal insulin analogs have been developed and are in late-phase clinical trials. One of these analogs is insulin icodec (icodec), appropriately developed to bind reversibly to albumin and to be gradually released into the patient’s circulation. Icodec has been tried mostly in clinical trials of adult patients with type 2 diabetes. A recent phase 3a clinical trial comprising adult patients with T1D was designed to evaluate icodec’s efficacy and safety compared with a daily basal insulin analog (degludec) after a 26-week main phase plus a safety extension of another 26 weeks. Icodec showed non-inferiority to once-daily degludec in glycated hemoglobin (HbA1c) reduction at week 26, and no significant differences in time in range (TIR) (70–180 mg/dL) and in time above range (TAR) (>180 mg/dL). On the other hand, it was associated with increased rates of clinically significant hypoglycemia (blood glucose < 54 mg/dL) and severe hypoglycemia (external assistance need for recovery), remaining either below or close to the internationally recommended targets for hypoglycemia. Another once-weekly insulin analog, basal insulin Fc (BIF), has been investigated in a phase 2 clinical trial comprising adult patients with T1D, with equally promising results. These preliminary data suggest that once-weekly insulin analogs could be of use for some patients with T1D, for example, patients not taking insulin regularly or those who are on MDI and wish for fewer injections. In addition, due to its prolonged mode of action, it could decrease the risk of diabetic ketoacidosis and the need for hospitalization. Additionally, patients with T1D that struggle with wearing diabetes mellitus devices/closed-loop insulin pumps either due to the cost or due to skin issues may also benefit from long-acting insulin. There is increasing evidence of the benefits of adjunctive therapies to insulin in T1D patients, but these therapies are not FDA-approved due to a possible higher risk of diabetic ketoacidosis. These long-acting insulin analogues could be used with adjunctive therapies in selected patients. This review aims to present available data on the mode of action, clinical trial results, and possible benefits of once-weekly insulin analogs for patients with T1D. In addition, it intends to suggest a future research framework for important clinical questions, such as once-weekly insulin analog use and exercise, sick days, or surgery, that will enhance our knowledge regarding this indisputable innovation in insulin management.
{"title":"Which Diabetes Patients Will Benefit the Most from Once-Weekly Basal Insulin Analogs? A Review with a Special Focus on Type 1 Diabetes Patients","authors":"Chrysoula Kosmeri, Maria S Baltogianni, V. Giapros, E. Siomou, V. Tsinopoulou, Foteini Balomenou, Anastasios Serbis","doi":"10.3390/endocrines5020015","DOIUrl":"https://doi.org/10.3390/endocrines5020015","url":null,"abstract":"Basal insulin analogs, typically administered once or twice daily, have been one of the two pillars of the multiple daily injection (MDI) insulin therapy of patients with type 1 diabetes (T1D) for the last twenty years. Recently, once-weekly basal insulin analogs have been developed and are in late-phase clinical trials. One of these analogs is insulin icodec (icodec), appropriately developed to bind reversibly to albumin and to be gradually released into the patient’s circulation. Icodec has been tried mostly in clinical trials of adult patients with type 2 diabetes. A recent phase 3a clinical trial comprising adult patients with T1D was designed to evaluate icodec’s efficacy and safety compared with a daily basal insulin analog (degludec) after a 26-week main phase plus a safety extension of another 26 weeks. Icodec showed non-inferiority to once-daily degludec in glycated hemoglobin (HbA1c) reduction at week 26, and no significant differences in time in range (TIR) (70–180 mg/dL) and in time above range (TAR) (>180 mg/dL). On the other hand, it was associated with increased rates of clinically significant hypoglycemia (blood glucose < 54 mg/dL) and severe hypoglycemia (external assistance need for recovery), remaining either below or close to the internationally recommended targets for hypoglycemia. Another once-weekly insulin analog, basal insulin Fc (BIF), has been investigated in a phase 2 clinical trial comprising adult patients with T1D, with equally promising results. These preliminary data suggest that once-weekly insulin analogs could be of use for some patients with T1D, for example, patients not taking insulin regularly or those who are on MDI and wish for fewer injections. In addition, due to its prolonged mode of action, it could decrease the risk of diabetic ketoacidosis and the need for hospitalization. Additionally, patients with T1D that struggle with wearing diabetes mellitus devices/closed-loop insulin pumps either due to the cost or due to skin issues may also benefit from long-acting insulin. There is increasing evidence of the benefits of adjunctive therapies to insulin in T1D patients, but these therapies are not FDA-approved due to a possible higher risk of diabetic ketoacidosis. These long-acting insulin analogues could be used with adjunctive therapies in selected patients. This review aims to present available data on the mode of action, clinical trial results, and possible benefits of once-weekly insulin analogs for patients with T1D. In addition, it intends to suggest a future research framework for important clinical questions, such as once-weekly insulin analog use and exercise, sick days, or surgery, that will enhance our knowledge regarding this indisputable innovation in insulin management.","PeriodicalId":72908,"journal":{"name":"Endocrines","volume":" 26","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140997320","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-06DOI: 10.3390/endocrines5020014
Allison L. B. Shapiro, Christina Coughlan, Brianne M. Bettcher, Meghan E. Pauley, Jeongchul Kim, Petter Bjornstad, Benjamin Rajic, Jennifer Truong, Christopher Bell, Y. Choi, Keenan A. Walker, Huntington Potter, A. Liese, Dana Dabelea, Christopher T. Whitlow
Adult-onset diabetes increases one’s risk of neurodegenerative disease including Alzheimer’s disease (AD); however, the risk associated with youth-onset diabetes (Y-DM) remains underexplored. We quantified plasma biomarkers of neurodegeneration and AD in participants with Y-DM from the SEARCH cohort at adolescence and young adulthood (Type 1, n = 25; Type 2, n = 25; 59% female; adolescence, age = 15 y/o [2.6]; adulthood, age = 27.4 y/o [2.2]), comparing them with controls (adolescence, n = 25, age = 14.8 y/o [2.7]; adulthood, n = 21, age = 24.9 y/o [2.8]). Plasma biomarkers, including glial fibrillary acidic protein (GFAP), neurofilament light chain protein (NfL), phosphorylated tau-181 (pTau181), and amyloid beta (Aβ40, Aβ42), were measured via Simoa. A subset of participants (n = 7; age = 27.5 y/o [5.7]) and six controls (age = 25.1 y/o [4.5]) underwent PET scans to quantify brain amyloid and tau densities in AD sensitive brain regions. Y-DM adolescents exhibited lower plasma levels of Aβ40, Aβ42, and GFAP, and higher pTau181 compared to controls (p < 0.05), a pattern persisting into adulthood (p < 0.001). All biomarkers showed significant increases from adolescence to adulthood in Y-DM (p < 0.01), though no significant differences in brain amyloid or tau were noted between Y-DM and controls in adulthood. Preliminary evidence suggests that preclinical AD neuropathology is present in young people with Y-DM, indicating a potential increased risk of neurodegenerative diseases.
{"title":"Biomarkers of Neurodegeneration and Alzheimer’s Disease Neuropathology in Adolescents and Young Adults with Youth-Onset Type 1 or Type 2 Diabetes: A Proof-of-Concept Study","authors":"Allison L. B. Shapiro, Christina Coughlan, Brianne M. Bettcher, Meghan E. Pauley, Jeongchul Kim, Petter Bjornstad, Benjamin Rajic, Jennifer Truong, Christopher Bell, Y. Choi, Keenan A. Walker, Huntington Potter, A. Liese, Dana Dabelea, Christopher T. Whitlow","doi":"10.3390/endocrines5020014","DOIUrl":"https://doi.org/10.3390/endocrines5020014","url":null,"abstract":"Adult-onset diabetes increases one’s risk of neurodegenerative disease including Alzheimer’s disease (AD); however, the risk associated with youth-onset diabetes (Y-DM) remains underexplored. We quantified plasma biomarkers of neurodegeneration and AD in participants with Y-DM from the SEARCH cohort at adolescence and young adulthood (Type 1, n = 25; Type 2, n = 25; 59% female; adolescence, age = 15 y/o [2.6]; adulthood, age = 27.4 y/o [2.2]), comparing them with controls (adolescence, n = 25, age = 14.8 y/o [2.7]; adulthood, n = 21, age = 24.9 y/o [2.8]). Plasma biomarkers, including glial fibrillary acidic protein (GFAP), neurofilament light chain protein (NfL), phosphorylated tau-181 (pTau181), and amyloid beta (Aβ40, Aβ42), were measured via Simoa. A subset of participants (n = 7; age = 27.5 y/o [5.7]) and six controls (age = 25.1 y/o [4.5]) underwent PET scans to quantify brain amyloid and tau densities in AD sensitive brain regions. Y-DM adolescents exhibited lower plasma levels of Aβ40, Aβ42, and GFAP, and higher pTau181 compared to controls (p < 0.05), a pattern persisting into adulthood (p < 0.001). All biomarkers showed significant increases from adolescence to adulthood in Y-DM (p < 0.01), though no significant differences in brain amyloid or tau were noted between Y-DM and controls in adulthood. Preliminary evidence suggests that preclinical AD neuropathology is present in young people with Y-DM, indicating a potential increased risk of neurodegenerative diseases.","PeriodicalId":72908,"journal":{"name":"Endocrines","volume":"51 10","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141009256","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-19DOI: 10.3390/endocrines5020012
Quiana C. Wilkerson-Vidal, Madushika M. Wimalarathne, Emily C. Hunt, Luis Mercado, Moses Adaji David, Christopher R. Apperson, Alan Smiley, Sharifa T. Love-Rutledge, Bernhard W. G. Vogler
Most patients with non-alcoholic steatohepatitis (NASH) have insulin resistance, and there is a near-universal association between NASH and insulin resistance. Insulin resistance induces lipid accumulation in the liver, leading to the development of metabolic syndrome. However, most NASH rodent models fail to develop metabolic syndrome. LEW.1WR1 rats that are 23 weeks old showed increased body mass, epididymal fat, and liver mass, suggesting obesity-driven metabolic dysfunction. We have characterized steatosis, inflammation, Mallory–Denk body formation with hematoxylin and eosin (H&E), and fibrosis with Trichome blue staining. The presence of hepatic fibrosis with other features of NASH described above is one of the major strengths of this model since most of the currently available NASH models do not develop microvesicular steatosis or fibrosis. Together with the other important features of NASH described above, we confirm that male LEW.1WR1 rats develop NASH and insulin resistance with a standard diet.
{"title":"Male LEW.1WR1 Rats Develop Metabolic Dysfunction, Steatohepatitis, and Liver Damage","authors":"Quiana C. Wilkerson-Vidal, Madushika M. Wimalarathne, Emily C. Hunt, Luis Mercado, Moses Adaji David, Christopher R. Apperson, Alan Smiley, Sharifa T. Love-Rutledge, Bernhard W. G. Vogler","doi":"10.3390/endocrines5020012","DOIUrl":"https://doi.org/10.3390/endocrines5020012","url":null,"abstract":"Most patients with non-alcoholic steatohepatitis (NASH) have insulin resistance, and there is a near-universal association between NASH and insulin resistance. Insulin resistance induces lipid accumulation in the liver, leading to the development of metabolic syndrome. However, most NASH rodent models fail to develop metabolic syndrome. LEW.1WR1 rats that are 23 weeks old showed increased body mass, epididymal fat, and liver mass, suggesting obesity-driven metabolic dysfunction. We have characterized steatosis, inflammation, Mallory–Denk body formation with hematoxylin and eosin (H&E), and fibrosis with Trichome blue staining. The presence of hepatic fibrosis with other features of NASH described above is one of the major strengths of this model since most of the currently available NASH models do not develop microvesicular steatosis or fibrosis. Together with the other important features of NASH described above, we confirm that male LEW.1WR1 rats develop NASH and insulin resistance with a standard diet.","PeriodicalId":72908,"journal":{"name":"Endocrines","volume":" 7","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140685174","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-17DOI: 10.3390/endocrines5020011
B. Arneth
Introduction: Insulin resistance is a common condition affecting thousands of people worldwide. This paper aims to examine the mechanisms underlying insulin resistance among people suffering from obesity. Methods and Design: This study entailed identifying articles related to insulin resistance and obesity. The publications were obtained using different electronic databases, including PubMed, EBSCO, and LILACS. The search terms included “insulin”, “resistance”, “obesity”, and “mechanisms”. Boolean operators were used to combine terms and phrases. Results: Insulin resistance is a physiological condition characterized by the impaired action of insulin in the body. The association between obesity and insulin resistance is linked to inflammatory, neural, and endocrine pathways that affect the sensitivity of organs to the level of insulin in the body. Discussion: Molecular studies have helped discover some of the fundamental mechanisms leading to the development of insulin resistance. Further investigations are needed to enhance our understanding of the connections among the inflammatory, neural, and cellular processes underlying the association between insulin resistance and obesity. Conclusion: This study revealed that a complex correlation exists between insulin resistance and obesity. This relationship involves a wide range of inflammatory, neural, and endocrine processes.
{"title":"Mechanisms of Insulin Resistance in Patients with Obesity","authors":"B. Arneth","doi":"10.3390/endocrines5020011","DOIUrl":"https://doi.org/10.3390/endocrines5020011","url":null,"abstract":"Introduction: Insulin resistance is a common condition affecting thousands of people worldwide. This paper aims to examine the mechanisms underlying insulin resistance among people suffering from obesity. Methods and Design: This study entailed identifying articles related to insulin resistance and obesity. The publications were obtained using different electronic databases, including PubMed, EBSCO, and LILACS. The search terms included “insulin”, “resistance”, “obesity”, and “mechanisms”. Boolean operators were used to combine terms and phrases. Results: Insulin resistance is a physiological condition characterized by the impaired action of insulin in the body. The association between obesity and insulin resistance is linked to inflammatory, neural, and endocrine pathways that affect the sensitivity of organs to the level of insulin in the body. Discussion: Molecular studies have helped discover some of the fundamental mechanisms leading to the development of insulin resistance. Further investigations are needed to enhance our understanding of the connections among the inflammatory, neural, and cellular processes underlying the association between insulin resistance and obesity. Conclusion: This study revealed that a complex correlation exists between insulin resistance and obesity. This relationship involves a wide range of inflammatory, neural, and endocrine processes.","PeriodicalId":72908,"journal":{"name":"Endocrines","volume":" 8","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140692694","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-03-27DOI: 10.3390/endocrines5020009
R. Paparodis, Ioannis Androulakis, Dimitrios P Askitis, Ilias Perogamvros, Nicholas Angelopoulos, Andreas Rizoulis, S. Livadas, A. Boniakos
Purpose: Lipid lowering treatments (LLTs) can reduce the risk of atherosclerotic cardiovascular disease (ASCVD). Despite the availability of potent LLTs, our clinical observations suggest an inadequate use of such agents. To evaluate this treatment deficit, we designed the present study. Methods: We reviewed the charts of all patients with a history of ASCVD (coronary artery disease—CAD; carotid stenosis—CS; or peripheral artery disease—PAD) diagnosed prior to their first visit to one of our clinics. We recorded their gender, age, ASCVD risk factors (diabetes, hypertension, tobacco use, body mass index), lipid values during that visit and the LLT used. We estimated the rates of the attainment of guideline-specific lipid goals by year, and assessed factors influencing the likelihood of treatment success. Results: Overall, n = 1003 subjects were recruited: CAD n = 703 (70.1%), PAD n = 168 (16.8%), CS n = 325 (32.4%); age 64.7 ± 11.2 years; n = 376 (37.5%) females; n = 642 (64.0%) had diabetes; n = 740 (73.8%) had hypertension; n = 299 (29.8%) were former and n = 367 (36.6%) were current smokers. An appropriate LLT was used in 361 (36.0%) subjects, n = 159 (15.9%) were on no treatment, n = 483 (48.2%) were receiving inadequate therapy, n = 434 (43.3%) were on a high-intensity LLT and n = 361 (36.0%) had achieved the year-specific LDL goals. Success rates ranged from 5.7% to 81.5%, with the lowest being 2020–2023 (5.7–14.5%), p < 0.001. The use of a combination of LLTs and PCSK9 inhibitors led to higher rates of LDL-C goals achievement (p < 0.001). Discussion: Recent secondary ASCVD risk prevention guidelines’ goals are rarely achieved in daily clinical practice, producing a major treatment deficit in this population. Newer systematic interventions are needed to curb this public health issue.
目的：降脂治疗（LLTs）可降低动脉粥样硬化性心血管疾病（ASCVD）的风险。尽管有强效降脂药，但我们的临床观察结果表明，此类药物的使用并不充分。为了评估这种治疗缺陷，我们设计了本研究。研究方法我们查阅了所有在首次就诊前确诊为 ASCVD（冠状动脉疾病-CAD；颈动脉狭窄-CS；或外周动脉疾病-PAD）患者的病历。我们记录了他们的性别、年龄、ASCVD 危险因素（糖尿病、高血压、吸烟、体重指数）、就诊时的血脂值和使用的 LLT。我们按年份估算了达到指南特定血脂目标的比率，并评估了影响治疗成功可能性的因素。结果：总共招募了 1003 名受试者：CAD n = 703 (70.1%)，PAD n = 168 (16.8%)，CS n = 325 (32.4%)；年龄 64.7 ± 11.2 岁；女性 n = 376 (37.5%)；糖尿病患者 n = 642 (64.0%)；高血压患者 n = 740 (73.8%)；曾经吸烟者 n = 299 (29.8%)，目前吸烟者 n = 367 (36.6%)。361名受试者（36.0%）接受了适当的低密度脂蛋白胆固醇治疗，159名受试者（15.9%）未接受任何治疗，483名受试者（48.2%）接受了不适当的治疗，434名受试者（43.3%）接受了高强度低密度脂蛋白胆固醇治疗，361名受试者（36.0%）达到了特定年份的低密度脂蛋白胆固醇目标。成功率从 5.7% 到 81.5%，最低的是 2020-2023 年（5.7%-14.5%），P < 0.001。联合使用 LLTs 和 PCSK9 抑制剂可提高低密度脂蛋白胆固醇目标的成功率（P < 0.001）。讨论：在日常临床实践中，近期的 ASCVD 二级风险预防指南的目标很少能实现，这在这一人群中造成了严重的治疗缺陷。需要更新的系统性干预措施来遏制这一公共卫生问题。
{"title":"Secondary Cardiovascular Disease Prevention Deficit Persists over the Years: A Multicenter Cross-Sectional Study Involving 1003 Consecutive Patients from Greece","authors":"R. Paparodis, Ioannis Androulakis, Dimitrios P Askitis, Ilias Perogamvros, Nicholas Angelopoulos, Andreas Rizoulis, S. Livadas, A. Boniakos","doi":"10.3390/endocrines5020009","DOIUrl":"https://doi.org/10.3390/endocrines5020009","url":null,"abstract":"Purpose: Lipid lowering treatments (LLTs) can reduce the risk of atherosclerotic cardiovascular disease (ASCVD). Despite the availability of potent LLTs, our clinical observations suggest an inadequate use of such agents. To evaluate this treatment deficit, we designed the present study. Methods: We reviewed the charts of all patients with a history of ASCVD (coronary artery disease—CAD; carotid stenosis—CS; or peripheral artery disease—PAD) diagnosed prior to their first visit to one of our clinics. We recorded their gender, age, ASCVD risk factors (diabetes, hypertension, tobacco use, body mass index), lipid values during that visit and the LLT used. We estimated the rates of the attainment of guideline-specific lipid goals by year, and assessed factors influencing the likelihood of treatment success. Results: Overall, n = 1003 subjects were recruited: CAD n = 703 (70.1%), PAD n = 168 (16.8%), CS n = 325 (32.4%); age 64.7 ± 11.2 years; n = 376 (37.5%) females; n = 642 (64.0%) had diabetes; n = 740 (73.8%) had hypertension; n = 299 (29.8%) were former and n = 367 (36.6%) were current smokers. An appropriate LLT was used in 361 (36.0%) subjects, n = 159 (15.9%) were on no treatment, n = 483 (48.2%) were receiving inadequate therapy, n = 434 (43.3%) were on a high-intensity LLT and n = 361 (36.0%) had achieved the year-specific LDL goals. Success rates ranged from 5.7% to 81.5%, with the lowest being 2020–2023 (5.7–14.5%), p < 0.001. The use of a combination of LLTs and PCSK9 inhibitors led to higher rates of LDL-C goals achievement (p < 0.001). Discussion: Recent secondary ASCVD risk prevention guidelines’ goals are rarely achieved in daily clinical practice, producing a major treatment deficit in this population. Newer systematic interventions are needed to curb this public health issue.","PeriodicalId":72908,"journal":{"name":"Endocrines","volume":"76 14","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140375959","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-03-18DOI: 10.3390/endocrines5010008
Saikat Fakir, N. Barabutis
GHRH regulates the secretion of GH from the anterior pituitary gland, previously associated with cancer progression and inflammation. An emerging body of evidence suggests that GHRHAnt support endothelial barrier function, but the mechanisms mediating these events are not completely understood. In the present study, it is demonstrated that the GHRHAnt JV-1-36 counteracts barrier dysfunction due to LPS or LTA treatment in HUVECs, utilizing the Dextran–FITC assay. Moreover, it is shown in BPAECs that these bacterial toxins increase ROS generation, and that this effect is counteracted by JV-1-36, which reinstates the redox balance. The possible involvement of NEK2 in the beneficial activities of GHRHAnt in IFN-γ- and LPS-triggered hyperpermeability was also assessed, since that kinase is involved in inflammatory responses. NEK2 was increased in the inflamed cells, and JV-1-36 counteracted those endothelial events. Our data support the beneficial effects of GHRHAnt in toxin-induced endothelial injury.
{"title":"Protective Activities of Growth Hormone-Releasing Hormone Antagonists against Toxin-Induced Endothelial Injury","authors":"Saikat Fakir, N. Barabutis","doi":"10.3390/endocrines5010008","DOIUrl":"https://doi.org/10.3390/endocrines5010008","url":null,"abstract":"GHRH regulates the secretion of GH from the anterior pituitary gland, previously associated with cancer progression and inflammation. An emerging body of evidence suggests that GHRHAnt support endothelial barrier function, but the mechanisms mediating these events are not completely understood. In the present study, it is demonstrated that the GHRHAnt JV-1-36 counteracts barrier dysfunction due to LPS or LTA treatment in HUVECs, utilizing the Dextran–FITC assay. Moreover, it is shown in BPAECs that these bacterial toxins increase ROS generation, and that this effect is counteracted by JV-1-36, which reinstates the redox balance. The possible involvement of NEK2 in the beneficial activities of GHRHAnt in IFN-γ- and LPS-triggered hyperpermeability was also assessed, since that kinase is involved in inflammatory responses. NEK2 was increased in the inflamed cells, and JV-1-36 counteracted those endothelial events. Our data support the beneficial effects of GHRHAnt in toxin-induced endothelial injury.","PeriodicalId":72908,"journal":{"name":"Endocrines","volume":"346 12","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140232619","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-03-06DOI: 10.3390/endocrines5010007
Guy Leclercq
The evolution of breast cancers results from the emergence of epithelial cell subpopulations containing variant Estrogen Receptor α which is able to bypass conventional treatments aimed at antagonizing the activity of this tumor-promoting receptor. The present investigation concerns a few estradiol derivates bearing substituents in position 11β that might not only contribute to the development of drugs to alleviate this unfortunate issue but that may be also helpful in identifying molecular aspects of resistance to this receptor in order to elaborate other therapeutic approaches. In this regard, AP-1 assisted and ERE-directed ERα transcriptions are demonstrated to be key factors in this area: AP-1 transcriptions are shown to antagonize ERE transcriptions, thereby limiting their tumor-promoting activity. This property results from a conformal change in the receptor, which is induced essentially by estrogenic ligands which, inserted into a cavity of ERα’s ligand-binding pocket, govern this regulatory mechanism. Flexible 11β side-chains favor this insertion, in contrast to their rigid counterparts, which counteract it; these properties give rise to strong estrogenic, SERM or SERD profiles. Suspected extracellular regulatory mechanisms resulting from these ligand-induced transcriptions are elaborated on in the present work in the context of breast cancer development.
{"title":"Antagonism of Estrogen Receptor α-Driven Transcription Mediated by AP-1 in Breast Cancer Therapy","authors":"Guy Leclercq","doi":"10.3390/endocrines5010007","DOIUrl":"https://doi.org/10.3390/endocrines5010007","url":null,"abstract":"The evolution of breast cancers results from the emergence of epithelial cell subpopulations containing variant Estrogen Receptor α which is able to bypass conventional treatments aimed at antagonizing the activity of this tumor-promoting receptor. The present investigation concerns a few estradiol derivates bearing substituents in position 11β that might not only contribute to the development of drugs to alleviate this unfortunate issue but that may be also helpful in identifying molecular aspects of resistance to this receptor in order to elaborate other therapeutic approaches. In this regard, AP-1 assisted and ERE-directed ERα transcriptions are demonstrated to be key factors in this area: AP-1 transcriptions are shown to antagonize ERE transcriptions, thereby limiting their tumor-promoting activity. This property results from a conformal change in the receptor, which is induced essentially by estrogenic ligands which, inserted into a cavity of ERα’s ligand-binding pocket, govern this regulatory mechanism. Flexible 11β side-chains favor this insertion, in contrast to their rigid counterparts, which counteract it; these properties give rise to strong estrogenic, SERM or SERD profiles. Suspected extracellular regulatory mechanisms resulting from these ligand-induced transcriptions are elaborated on in the present work in the context of breast cancer development.","PeriodicalId":72908,"journal":{"name":"Endocrines","volume":"140 36","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140078330","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-02-05DOI: 10.3390/endocrines5010006
Simonetta Marucci, Luca Busetto, Marco Chianelli, Alessandra Fusco, Maria Carpentieri, Marina Armellini, Francesco Tassone, Marcello Sciaraffia, Maria Chantal Ponziani, A. Nelva, Carla Micaela Cuttica
Binge eating disorder (BED) is the most common eating disorder categorized in the DSM-V, but it is often not diagnosed in patients with obesity because it can be difficult to detect in these patients who often have altered eating patterns. In this narrative review, we have highlighted the most recent findings in the screening, diagnosis, and treatment of patients with BED and obesity. The results of our search showed that many BED patients are not obese, and most people with obesity do not have binge behavior. In the diagnostic assessment of these patients, it is important to evaluate not only the clinical and nutritional status and the presence of medical comorbidities, but also the psychological signs and symptoms related to psychiatric comorbidities to define the appropriate diagnosis and the consequent level of treatment. Well-tolerated drugs with action on both body weight and binges can be useful as a second-line complement to cognitive behavioral therapy (CBT). Specific guidelines are needed to obtain consensus on appropriate recommendations in patients with obesity and BED approaching bariatric surgery, taking into account not only weight reduction and clinical data, but also eating behaviors. Identification of BED is important for targeting individuals at high risk of obesity, adverse metabolic patterns, and cardiovascular disease. The challenge is to also achieve lasting weight loss in patients with BED and concomitant obesity.
暴饮暴食症（BED）是 DSM-V 分类中最常见的饮食失调症，但肥胖症患者往往不能确诊为暴饮暴食症，因为肥胖症患者的饮食模式经常发生改变，很难发现暴饮暴食症。在这篇叙述性综述中，我们重点介绍了在筛查、诊断和治疗 BED 和肥胖症患者方面的最新研究成果。我们的研究结果表明，许多 BED 患者并不肥胖，大多数肥胖症患者也没有暴饮暴食行为。在对这些患者进行诊断评估时，不仅要评估临床和营养状况以及是否存在内科合并症，还要评估与精神科合并症相关的心理症状和体征，以确定适当的诊断和相应的治疗水平。作为认知行为疗法（CBT）的二线补充，对体重和暴饮暴食均有作用的耐受性良好的药物可以发挥作用。对于即将接受减肥手术的肥胖症和 BED 患者，需要制定具体的指南，以就适当的建议达成共识，不仅要考虑减轻体重和临床数据，还要考虑进食行为。对于肥胖、不良代谢模式和心血管疾病高风险人群来说，识别 BED 非常重要。同时，如何使 BED 和合并肥胖症的患者实现持久的体重减轻也是一项挑战。
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Pub Date : 2024-02-05DOI: 10.3390/endocrines5010006
Simonetta Marucci, Luca Busetto, Marco Chianelli, Alessandra Fusco, Maria Carpentieri, Marina Armellini, Francesco Tassone, Marcello Sciaraffia, Maria Chantal Ponziani, A. Nelva, Carla Micaela Cuttica
Binge eating disorder (BED) is the most common eating disorder categorized in the DSM-V, but it is often not diagnosed in patients with obesity because it can be difficult to detect in these patients who often have altered eating patterns. In this narrative review, we have highlighted the most recent findings in the screening, diagnosis, and treatment of patients with BED and obesity. The results of our search showed that many BED patients are not obese, and most people with obesity do not have binge behavior. In the diagnostic assessment of these patients, it is important to evaluate not only the clinical and nutritional status and the presence of medical comorbidities, but also the psychological signs and symptoms related to psychiatric comorbidities to define the appropriate diagnosis and the consequent level of treatment. Well-tolerated drugs with action on both body weight and binges can be useful as a second-line complement to cognitive behavioral therapy (CBT). Specific guidelines are needed to obtain consensus on appropriate recommendations in patients with obesity and BED approaching bariatric surgery, taking into account not only weight reduction and clinical data, but also eating behaviors. Identification of BED is important for targeting individuals at high risk of obesity, adverse metabolic patterns, and cardiovascular disease. The challenge is to also achieve lasting weight loss in patients with BED and concomitant obesity.
暴饮暴食症（BED）是 DSM-V 分类中最常见的饮食失调症，但肥胖症患者往往不能确诊为暴饮暴食症，因为肥胖症患者的饮食模式经常发生改变，很难发现暴饮暴食症。在这篇叙述性综述中，我们重点介绍了在筛查、诊断和治疗 BED 和肥胖症患者方面的最新研究成果。我们的研究结果表明，许多 BED 患者并不肥胖，大多数肥胖症患者也没有暴饮暴食行为。在对这些患者进行诊断评估时，不仅要评估临床和营养状况以及是否存在内科合并症，还要评估与精神科合并症相关的心理症状和体征，以确定适当的诊断和相应的治疗水平。作为认知行为疗法（CBT）的二线补充，对体重和暴饮暴食均有作用的耐受性良好的药物可以发挥作用。对于即将接受减肥手术的肥胖症和 BED 患者，需要制定具体的指南，以就适当的建议达成共识，不仅要考虑减轻体重和临床数据，还要考虑进食行为。对于肥胖、不良代谢模式和心血管疾病高风险人群来说，识别 BED 非常重要。同时，如何使 BED 和合并肥胖症的患者实现持久的体重减轻也是一项挑战。
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Pub Date : 2024-02-01DOI: 10.3390/endocrines5010004
Juliette d’Otreppe, Daniel Patiño-García, Patryk Piekos, Matthieu de Codt, Diego D. Manavella, G. Courtoy, Renán Orellana
Adenomyosis (ADM) is a multifaceted uterine pathology characterized by the ectopic infiltration of endometrial tissue into the myometrium, affecting approximately 20% of women in the reproductive age group seeking gynecological care. This condition manifests as a range of debilitating symptoms, including dysmenorrhea, menorrhagia, impaired fertility, and heightened susceptibility to miscarriage and obstetric complications. Substantial research has been dedicated to exploring its underlying molecular mechanisms and developing non-invasive precision medical therapies. ADM is primarily characterized by a dysregulation in sex steroid hormone homeostasis, particularly estrogen and progesterone. However, emerging evidence suggests that additional endocrine mediators and disruptors may play contributory roles in the etiology of ADM. Genetic and epigenetic alterations of endocrine signaling pathways have been implicated as prevailing mechanisms underlying the development and progression of the disease. The present review aims to provide an updated and comprehensive overview of the current understanding of the pathophysiology of ADM, with a particular emphasis on the dysregulated hormonal milieu and the potential involvement of endocrine disruptors. By elucidating these intricate molecular mechanisms, this review seeks to pave the way for novel research directions in the development of targeted therapeutic strategies for ADM management.
{"title":"Exploring the Endocrine Mechanisms in Adenomyosis: From Pathogenesis to Therapies","authors":"Juliette d’Otreppe, Daniel Patiño-García, Patryk Piekos, Matthieu de Codt, Diego D. Manavella, G. Courtoy, Renán Orellana","doi":"10.3390/endocrines5010004","DOIUrl":"https://doi.org/10.3390/endocrines5010004","url":null,"abstract":"Adenomyosis (ADM) is a multifaceted uterine pathology characterized by the ectopic infiltration of endometrial tissue into the myometrium, affecting approximately 20% of women in the reproductive age group seeking gynecological care. This condition manifests as a range of debilitating symptoms, including dysmenorrhea, menorrhagia, impaired fertility, and heightened susceptibility to miscarriage and obstetric complications. Substantial research has been dedicated to exploring its underlying molecular mechanisms and developing non-invasive precision medical therapies. ADM is primarily characterized by a dysregulation in sex steroid hormone homeostasis, particularly estrogen and progesterone. However, emerging evidence suggests that additional endocrine mediators and disruptors may play contributory roles in the etiology of ADM. Genetic and epigenetic alterations of endocrine signaling pathways have been implicated as prevailing mechanisms underlying the development and progression of the disease. The present review aims to provide an updated and comprehensive overview of the current understanding of the pathophysiology of ADM, with a particular emphasis on the dysregulated hormonal milieu and the potential involvement of endocrine disruptors. By elucidating these intricate molecular mechanisms, this review seeks to pave the way for novel research directions in the development of targeted therapeutic strategies for ADM management.","PeriodicalId":72908,"journal":{"name":"Endocrines","volume":"8 5","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139878555","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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