S. F. Petry, Naga Deepa Kandula, S. Günther, Christian S. M. Helker, U. Schagdarsurengin, T. Linn
Non-mesenchymal pancreatic cells are a potential source for cell replacement. Their transdifferentiation can be achieved by triggering epigenetic remodeling through e. g. post-translational modification of histones. Valproic acid, a branched-chain saturated fatty acid with histone deacetylase inhibitor activity, was linked to the expression of key transcription factors of pancreatic lineage in epithelial cells and insulin transcription. However, the potential of valproic acid to cause cellular reprogramming is not fully understood. To shed further light on it we employed next-generation RNA sequencing, real-time PCR, and protein analyses by ELISA and western blot, to assess the impact of valproic acid on transcriptome and function of Panc-1-cells. Our results indicate that valproic acid has a significant impact on the cell cycle, cell adhesion, histone H3 acetylation, and metabolic pathways as well as the initiation of epithelial-mesenchymal transition through acetylation of histone H3 resulting in α-cell-like characteristics. We conclude that human epithelial pancreatic cells can be transdifferentiated into cells with endocrine properties through epigenetic regulation by valproic acid favoring an α-cell-like phenotype.
{"title":"Valproic Acid Initiates Transdifferentiation of the Human Ductal Adenocarcinoma Cell-line Panc-1 Into α-Like Cells.","authors":"S. F. Petry, Naga Deepa Kandula, S. Günther, Christian S. M. Helker, U. Schagdarsurengin, T. Linn","doi":"10.1055/a-1750-9190","DOIUrl":"https://doi.org/10.1055/a-1750-9190","url":null,"abstract":"Non-mesenchymal pancreatic cells are a potential source for cell replacement. Their transdifferentiation can be achieved by triggering epigenetic remodeling through e. g. post-translational modification of histones. Valproic acid, a branched-chain saturated fatty acid with histone deacetylase inhibitor activity, was linked to the expression of key transcription factors of pancreatic lineage in epithelial cells and insulin transcription. However, the potential of valproic acid to cause cellular reprogramming is not fully understood. To shed further light on it we employed next-generation RNA sequencing, real-time PCR, and protein analyses by ELISA and western blot, to assess the impact of valproic acid on transcriptome and function of Panc-1-cells. Our results indicate that valproic acid has a significant impact on the cell cycle, cell adhesion, histone H3 acetylation, and metabolic pathways as well as the initiation of epithelial-mesenchymal transition through acetylation of histone H3 resulting in α-cell-like characteristics. We conclude that human epithelial pancreatic cells can be transdifferentiated into cells with endocrine properties through epigenetic regulation by valproic acid favoring an α-cell-like phenotype.","PeriodicalId":94001,"journal":{"name":"Experimental and clinical endocrinology & diabetes : official journal, German Society of Endocrinology [and] German Diabetes Association","volume":"12 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87102633","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}
Erwin Schleicher, Christian Gerdes, A. Petersmann, D. Müller-Wieland, U. Müller, G. Freckmann, L. Heinemann, M. Nauck, R. Landgraf
{"title":"Definition, Classification and Diagnosis of Diabetes Mellitus.","authors":"Erwin Schleicher, Christian Gerdes, A. Petersmann, D. Müller-Wieland, U. Müller, G. Freckmann, L. Heinemann, M. Nauck, R. Landgraf","doi":"10.1055/a-1624-2897","DOIUrl":"https://doi.org/10.1055/a-1624-2897","url":null,"abstract":"","PeriodicalId":94001,"journal":{"name":"Experimental and clinical endocrinology & diabetes : official journal, German Society of Endocrinology [and] German Diabetes Association","volume":"13 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78340683","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}
{"title":"Diabetes and Fatty Liver.","authors":"N. Stefan, M. Roden","doi":"10.1055/a-1624-3541","DOIUrl":"https://doi.org/10.1055/a-1624-3541","url":null,"abstract":"","PeriodicalId":94001,"journal":{"name":"Experimental and clinical endocrinology & diabetes : official journal, German Society of Endocrinology [and] German Diabetes Association","volume":"2012 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82640427","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}
Sandra Schlüter, D. Deiss, B. Gehr, K. Lange, S. von Sengbusch, A. Thomas, R. Ziegler, G. Freckmann
{"title":"Glucose Measurement and Control in Patients with Type 1 or Type 2 Diabetes.","authors":"Sandra Schlüter, D. Deiss, B. Gehr, K. Lange, S. von Sengbusch, A. Thomas, R. Ziegler, G. Freckmann","doi":"10.1055/a-1624-3282","DOIUrl":"https://doi.org/10.1055/a-1624-3282","url":null,"abstract":"","PeriodicalId":94001,"journal":{"name":"Experimental and clinical endocrinology & diabetes : official journal, German Society of Endocrinology [and] German Diabetes Association","volume":"90 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90349898","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}
OBJECTIVE Due to the growing diabetes pandemic, the number of colonoscopies performed in patients with diabetes is steadily rising. However, recommendations on adjustments of anti-hyperglycaemic agents (AHG) during bowel preparation for colonoscopy are limited. METHODS A total of nine articles were revealed on a PubMed search using the search terms "diabetes" and "colonoscopy", "sigmoidoscopy", "endoscopy", "endoscopic intervention", "endoscopic invasive diagnostics", "endoscopic surgery", or "diabetes care in the hospital" and manual screening of the references of the articles reporting on AHG adjustment during bowel preparation. RESULTS Regular glucose measurements and the opportunity to contact the diabetes team were commonly advised. Recommendations also agreed that all oral AHG and short-acting insulin should be omitted when patients are on clear fluids. Recent studies suggest discontinuation of sodium-glucose cotransporter-2 (SGLT2) inhibitors even three days before the colonoscopy. In contrast, recommendations differed regarding adjustment of basal insulin depending on diabetes type and time point in relation to the intervention. CONCLUSIONS While discontinuation of oral AHG and short-acting insulin during bowel preparation for colonoscopy is generally accepted, recommendations on the adaptation of basal insulin follow different approaches.
{"title":"Adjustment of Anti-Hyperglycaemic Agents During Bowel Preparation for Colonoscopy in Patients with Diabetes.","authors":"K. Müssig, H. Adamek","doi":"10.1055/a-1782-9389","DOIUrl":"https://doi.org/10.1055/a-1782-9389","url":null,"abstract":"OBJECTIVE\u0000Due to the growing diabetes pandemic, the number of colonoscopies performed in patients with diabetes is steadily rising. However, recommendations on adjustments of anti-hyperglycaemic agents (AHG) during bowel preparation for colonoscopy are limited.\u0000\u0000\u0000METHODS\u0000A total of nine articles were revealed on a PubMed search using the search terms \"diabetes\" and \"colonoscopy\", \"sigmoidoscopy\", \"endoscopy\", \"endoscopic intervention\", \"endoscopic invasive diagnostics\", \"endoscopic surgery\", or \"diabetes care in the hospital\" and manual screening of the references of the articles reporting on AHG adjustment during bowel preparation.\u0000\u0000\u0000RESULTS\u0000Regular glucose measurements and the opportunity to contact the diabetes team were commonly advised. Recommendations also agreed that all oral AHG and short-acting insulin should be omitted when patients are on clear fluids. Recent studies suggest discontinuation of sodium-glucose cotransporter-2 (SGLT2) inhibitors even three days before the colonoscopy. In contrast, recommendations differed regarding adjustment of basal insulin depending on diabetes type and time point in relation to the intervention.\u0000\u0000\u0000CONCLUSIONS\u0000While discontinuation of oral AHG and short-acting insulin during bowel preparation for colonoscopy is generally accepted, recommendations on the adaptation of basal insulin follow different approaches.","PeriodicalId":94001,"journal":{"name":"Experimental and clinical endocrinology & diabetes : official journal, German Society of Endocrinology [and] German Diabetes Association","volume":"126 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91473300","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}
C. Baechle, A. Stahl-Pehe, K. Castillo, R. Holl, J. Rosenbauer
OBJECTIVE To analyze the cross-sectional associations of family structure with mental health and attention deficit (hyperactivity) disorders (AD(H)D) in 11- to 17-year-old adolescents with early-onset type 1 diabetes participating in one of three baseline surveys as part of an ongoing cohort study. METHODS Parents (n=1,631) completed the Strengths and Difficulties Questionnaire to screen for their child's mental health and answered questions about their child's diagnosis of AD(H)D. Associations between mental health or AD(H)D and family structure were analyzed using multivariable logistic regression analyses adjusted for various personal and diabetes-related variables. RESULTS Compared to adolescents living with both parents, adolescents living with one parent and his/her partner had 2.35 (95% confidence interval 1.32; 4.21) higher odds of abnormal screening result and 2.08 (1.09; 3.95) higher odds of a borderline screening result while adolescents living with a single parent had 1.84 (1.07; 3.17)/1.08 (0.53; 2.21) higher odds of abnormal/borderline screening results. The odds ratios for diagnosed attention deficit (hyperactivity) disorder were 2.17 (0.98; 4.84) for adolescents living with one parent and his/her partner and 1.27 (0.54; 3.01) for those living with a single parent vs. both parents. CONCLUSIONS Our results indicate higher odds of mental health problems and AD(H)D in adolescents with type 1 diabetes who do not live with both parents; this finding was most pronounced in individuals living with one parent and his/her partner vs. both parents. Longitudinal studies are needed to verify our results and elucidate the underlying mechanisms.
{"title":"Family Structure is Associated with Mental Health and Attention Deficit (Hyperactivity) Disorders in Adolescents with Type 1 Diabetes.","authors":"C. Baechle, A. Stahl-Pehe, K. Castillo, R. Holl, J. Rosenbauer","doi":"10.1055/a-1729-7972","DOIUrl":"https://doi.org/10.1055/a-1729-7972","url":null,"abstract":"OBJECTIVE\u0000To analyze the cross-sectional associations of family structure with mental health and attention deficit (hyperactivity) disorders (AD(H)D) in 11- to 17-year-old adolescents with early-onset type 1 diabetes participating in one of three baseline surveys as part of an ongoing cohort study.\u0000\u0000\u0000METHODS\u0000Parents (n=1,631) completed the Strengths and Difficulties Questionnaire to screen for their child's mental health and answered questions about their child's diagnosis of AD(H)D. Associations between mental health or AD(H)D and family structure were analyzed using multivariable logistic regression analyses adjusted for various personal and diabetes-related variables.\u0000\u0000\u0000RESULTS\u0000Compared to adolescents living with both parents, adolescents living with one parent and his/her partner had 2.35 (95% confidence interval 1.32; 4.21) higher odds of abnormal screening result and 2.08 (1.09; 3.95) higher odds of a borderline screening result while adolescents living with a single parent had 1.84 (1.07; 3.17)/1.08 (0.53; 2.21) higher odds of abnormal/borderline screening results. The odds ratios for diagnosed attention deficit (hyperactivity) disorder were 2.17 (0.98; 4.84) for adolescents living with one parent and his/her partner and 1.27 (0.54; 3.01) for those living with a single parent vs. both parents.\u0000\u0000\u0000CONCLUSIONS\u0000Our results indicate higher odds of mental health problems and AD(H)D in adolescents with type 1 diabetes who do not live with both parents; this finding was most pronounced in individuals living with one parent and his/her partner vs. both parents. Longitudinal studies are needed to verify our results and elucidate the underlying mechanisms.","PeriodicalId":94001,"journal":{"name":"Experimental and clinical endocrinology & diabetes : official journal, German Society of Endocrinology [and] German Diabetes Association","volume":"46 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84064542","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}
K. Parhofer, A. Birkenfeld, W. Krone, M. Lehrke, N. Marx, M. Merkel, K. Schütt, A. Zirlik, D. Müller-Wieland
Hypertension,
高血压
{"title":"Position Paper on Lipid Therapy in Patients with Diabetes Mellitus.","authors":"K. Parhofer, A. Birkenfeld, W. Krone, M. Lehrke, N. Marx, M. Merkel, K. Schütt, A. Zirlik, D. Müller-Wieland","doi":"10.1055/a-1624-3572","DOIUrl":"https://doi.org/10.1055/a-1624-3572","url":null,"abstract":"Hypertension,","PeriodicalId":94001,"journal":{"name":"Experimental and clinical endocrinology & diabetes : official journal, German Society of Endocrinology [and] German Diabetes Association","volume":"139 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86820536","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}
K. Schütt, T. Forst, A. Birkenfeld, A. Zirlik, D. Müller-Wieland, N. Marx
{"title":"Diabetes Mellitus and the Heart.","authors":"K. Schütt, T. Forst, A. Birkenfeld, A. Zirlik, D. Müller-Wieland, N. Marx","doi":"10.1055/a-1624-3593","DOIUrl":"https://doi.org/10.1055/a-1624-3593","url":null,"abstract":"","PeriodicalId":94001,"journal":{"name":"Experimental and clinical endocrinology & diabetes : official journal, German Society of Endocrinology [and] German Diabetes Association","volume":"103 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81917229","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}
T. Skurk, A. Bosy-Westphal, A. Grünerbel, S. Kabisch, W. Keuthage, P. Kronsbein, K. Müssig, A. Pfeiffer, M. Simon, A. Tombek, K. Weber, Diana Rubin
{"title":"Dietary recommendations for persons with type 2 diabetes mellitus.","authors":"T. Skurk, A. Bosy-Westphal, A. Grünerbel, S. Kabisch, W. Keuthage, P. Kronsbein, K. Müssig, A. Pfeiffer, M. Simon, A. Tombek, K. Weber, Diana Rubin","doi":"10.1055/a-1624-5095","DOIUrl":"https://doi.org/10.1055/a-1624-5095","url":null,"abstract":"","PeriodicalId":94001,"journal":{"name":"Experimental and clinical endocrinology & diabetes : official journal, German Society of Endocrinology [and] German Diabetes Association","volume":"10 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82036944","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}
Thyroid hormone receptors are nuclear receptors that function as transcription factors and are regulated by thyroid hormones. To date, a number of variants and isoforms are known. This review focuses on the thyroid hormone receptor α (TRα), in particular TRα2, an isoform that arises from alternative splicing of the THRA mRNA transcript. Unlike the TRα1 isoform, which can bind T3, the TRα2 isoform lacks a ligand-binding domain but still binds to DNA thereby antagonizing the transcriptional activity of TRα1. Although a regulatory role has been proposed, the physiological function of this TRα2 antagonism is still unclear due to limited in vitro and mouse model data. Recently, the first patients with resistance to thyroid hormone due to mutations in THRA, the TRα encoding gene, affecting the antagonistic function of TRα2 were described, suggesting a significant role of this particular isoform in human physiology.
{"title":"What is the Role of Thyroid Hormone Receptor Alpha 2 (TRα2) in Human Physiology?","authors":"Sarah Paisdzior, Marc Schuelke, H. Krude","doi":"10.1055/a-1716-7980","DOIUrl":"https://doi.org/10.1055/a-1716-7980","url":null,"abstract":"Thyroid hormone receptors are nuclear receptors that function as transcription factors and are regulated by thyroid hormones. To date, a number of variants and isoforms are known. This review focuses on the thyroid hormone receptor α (TRα), in particular TRα2, an isoform that arises from alternative splicing of the THRA mRNA transcript. Unlike the TRα1 isoform, which can bind T3, the TRα2 isoform lacks a ligand-binding domain but still binds to DNA thereby antagonizing the transcriptional activity of TRα1. Although a regulatory role has been proposed, the physiological function of this TRα2 antagonism is still unclear due to limited in vitro and mouse model data. Recently, the first patients with resistance to thyroid hormone due to mutations in THRA, the TRα encoding gene, affecting the antagonistic function of TRα2 were described, suggesting a significant role of this particular isoform in human physiology.","PeriodicalId":94001,"journal":{"name":"Experimental and clinical endocrinology & diabetes : official journal, German Society of Endocrinology [and] German Diabetes Association","volume":"3 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77314056","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}