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Specialty: Endocrinology

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Total 648 results found since Jan 2013.

Adiponectin treatment improves insulin resistance in mice by regulating the expression of the mitochondrial-derived peptide MOTS-c and its response to exercise via APPL1 –SIRT1–PGC-1α
Conclusions/interpretationOur findings showed that the APPL1 –SIRT1–PGC-1α pathway regulates the production and/or secretion of skeletal muscle MOTS-c by mediating adiponectin signalling. Our study provides an insight into the cellular and molecular pathways underlying the pathogenesis of diabetes and shows that MOTS-c is a potential novel therapeutic ta rget in the treatment of diabetes.Graphical abstract
Source: Diabetologia - September 2, 2020 Category: Endocrinology Source Type: research

GPR120 regulates pancreatic polypeptide secretion from male mouse islets via PLC-mediated calcium mobilization.
In this study, GPR120-IRES-EGFP knockin (KI) mouse was generated to identify GPR120-expressing cells with enhance green fluorescence proteins (EGFP). EGFP-positive cells collected from the KI mouse islets by flow cytometry had significantly higher expression of pancreatic polypeptide (PP) evidenced by RT-qPCR. Single cell RT-PCR and immunocytochemical double staining also demonstrated the co-expression of GPR120 with PP in mouse islets. GPR120 specific agonist, TUG-891, significantly increased plasma PP levels in mice. TUG-891 significantly increased PP levels in islet medium in vitro, which was markedly attenuated by GPR1...
Source: Endocrinology - September 1, 2020 Category: Endocrinology Authors: Zhao YF, Li XC, Liang XY, Zhao YY, Xie R, Zhang LJ, Zhang XC, Chen C Tags: Endocrinology Source Type: research

Liver-Specific Knockdown of Class IIa HDACs Has Limited Efficacy on Glucose Metabolism but Entails Severe Organ Side Effects in Mice
In conclusion, the liver-directed combinatorial knockdown of HDAC4, 5 and 7 by therapeutic siRNAs affected multiple pathways in vitro, leading in vivo to the downregulation of genes involved in gluconeogenesis. However, the effects on gene expression level were not paralleled by a significant reduction of gluconeogenesis in mice. Combined knockdown of HDAC isoforms was associated with severe adverse effects in vivo, challenging this approach as a treatment option for chronic metabolic disorders like type 2 diabetes.
Source: Frontiers in Endocrinology - August 27, 2020 Category: Endocrinology Source Type: research

Differential Role of Smad2 and Smad3 in the Acquisition of an Endovascular Trophoblast-Like Phenotype and Preeclampsia
In this study, we determined Smad2 and Smad3 expression pattern in placenta and their effects on trophoblast invasion and differentiation. Total Smad2/3 levels were relatively constant across gestation while the ratio of active phosphorylated forms to their total levels varied with gestational stages, with a higher pSmad2/total Smad2 in later gestation and a higher pSmad3/total Smad3 in early gestation. Immunofluorescent staining revealed that pSmad3 was localized in nuclei of EVTs in anchoring villi. On the other hand, pSmad2 was mostly absent in this invasive EVT population. In addition, pSmad3/total Smad3, but not pSmad...
Source: Frontiers in Endocrinology - July 7, 2020 Category: Endocrinology Source Type: research

Silencing of NAMPT leads to up-regulation of insulin receptor substrate 1 gene expression in U87 glioma cells.
CONCLUSIONS: Results of this investigation demonstrated that silencing of NAMPT mRNA with corresponding down-regulation of NAMPT protein and suppression of the glioma cell proliferation affected the expression of IRS1 gene as well as many other genes encoding the proliferation related proteins. It is possible that dysregulation of most of the studied genes in glioma cells after silencing of NAMPT is reflected by a complex of intergenic interactions and that NAMPT is an important factor for genome stability and regulatory mechanisms contributing to the control of glioma cell metabolism and proliferation. PMID: 32597148 ...
Source: Endocrine Regulations - July 2, 2020 Category: Endocrinology Tags: Endocr Regul Source Type: research

Bisphenol A induces Agrp gene expression in hypothalamic neurons through a mechanism involving ATF3.
Conclusions: Overall, these results indicate hypothalamic Agrp is susceptible to dysregulation by BPA and implicate ATF3 as a common mediator of the orexigenic effects of BPA in hypothalamic neurons.
Source: Neuroendocrinology - June 22, 2020 Category: Endocrinology Source Type: research

MiD51 Is Important for Maintaining Mitochondrial Health in Pancreatic Islet and MIN6 Cells
Conclusion: We have demonstrated that MiD51 plays a pivotal role in regulating mitochondrial function and hence insulin secretion in MIN6 cells. We propose that this anchor protein of Drp1 is important to maintain a homogeneous mitochondrial network and to avoid morphologies such as hyperelongation and clustering which are inaccessible for degradation by autophagy. Assuming that insulin granule degradation frequently suppresses autophagy in beta cells, MiD51 could be a key element maintaining mitochondrial health.
Source: Frontiers in Endocrinology - April 27, 2020 Category: Endocrinology Source Type: research

Transforming growth factor- β1 suppress pentraxin-3 in human orbital fibroblasts
ConclusionThese findings indicated that TGF- β1 can inhibit PTX3 expression in human OFs, which may participate in inflammation and fibrosis in patients with TAO and provide a potential target for the antifibrotic treatment.
Source: Endocrine - April 15, 2020 Category: Endocrinology Source Type: research

Systemic Delivery of siRNA Specific for Silencing TLR4 Gene Expression Reduces Diabetic Cardiomyopathy in a Mouse Model of Streptozotocin-Induced Type  1 Diabetes
ConclusionOur study used siRNA to specifically silence TLR4 gene expression in the diabetic mouse heart in vivo and to investigate the role that TLR4 plays in diabetic cardiomyopathy. It is likely that silencing of the TLR4 gene through siRNA could prevent the development of diabetic cardiomyopathy.
Source: Diabetes Therapy - April 12, 2020 Category: Endocrinology Source Type: research

The inducible β5i proteasome subunit contributes to proinsulin degradation in GRP94 deficient β cells and is overexpressed in type 2 diabetes pancreatic islets.
Abstract Proinsulin is a misfolding-prone protein and its efficient breakdown is critical, when b-cells are confronted with high insulin biosynthetic demands, to prevent endoplasmic reticulum stress, a key trigger of secretory dysfunction and, if uncompensated, apoptosis. Proinsulin degradation is thought to be performed by the constitutively expressed standard proteasome, while the roles of other proteasomes are unknown. We recently demonstrated that deficiency of the proinsulin chaperone GRP94 causes impaired proinsulin-handling and defective insulin-secretion associated with a compensated endoplasmic reticulum ...
Source: Am J Physiol Endocri... - April 6, 2020 Category: Endocrinology Authors: Khilji MS, Bresson SE, Verstappen D, Pihl C, Andersen PAK, Agergaard JB, Dahlby T, Holgersen Bryde T, Klindt K, Nielsen CK, Walentinsson A, Zivkovic D, Bousquet MP, Tyrberg B, Richardson SJ, Morgan NG, Mandrup-Poulsen T, Marzec MT Tags: Am J Physiol Endocrinol Metab Source Type: research

Interleukin-6 (IL-6) activates the NOTCH1 signaling pathway through E-proteins in endometriotic lesions.
CONCLUSIONS: IL-6 induced NOTCH1 expression is mediated by E-proteins in the ectopic GE cells, which may promote endometriotic lesion development. PMID: 32119078 [PubMed - as supplied by publisher]
Source: The Journal of Clinical Endocrinology and Metabolism - March 1, 2020 Category: Endocrinology Authors: Song Y, Su RW, Joshi NR, Kim TH, Lessey BA, Jeong JW, Fazleabas AT Tags: J Clin Endocrinol Metab Source Type: research

Stat3 activation induces insulin resistance via a muscle-specific E3 ubiquitin ligase Fbxo40.
Abstract Cellular mechanisms causing insulin resistance (IR) in chronic kidney disease (CKD) are poorly understood. One potential mechanism is that CKD-induced inflammation activates the signal transducer and activator of transcription 3 (Stat3) in muscle. We uncovered increased p-Stat3 in muscles of mice with CKD or mice fed high fat diet (HFD). Activated Stat3 stimulates the expression of Fbxo40, a muscle-specific E3 ubiquitin ligase that stimulates ubiquitin conjugation leading to degradation of insulin receptor substrate 1 (IRS1). Evidence that STAT3 activates Fbxo40 includes: 1) potential Stat3 binding sites ...
Source: Am J Physiol Endocri... - February 25, 2020 Category: Endocrinology Authors: Zhang L, Chen Z, Wang Y, Tweardy DJ, Mitch WE Tags: Am J Physiol Endocrinol Metab Source Type: research

Adipose TBX1 Regulates β-Adrenergic Sensitivity in Subcutaneous Adipose Tissue and Thermogenic Capacity In Vivo
Conclusions: Adipose expression of TBX1 is necessary, but not sufficient, to defend body temperature during cold via proper UCP1 expression. Adipose TBX1 expression was also required for proper insulin signaling in subcutaneous adipose as well as maintaining β-adrenergic sensitivity but overexpression of TBX1 was not sufficient to induce adipocyte beiging or prevent diet induced obesity. TBX1 expression is enriched in adipose stem cells in which it has contrasting effects on adipogenesis in mouse versus human cells. Collectively, these data demonstrate the importance of adipose TBX1 in the regulation of beige adipocyte fu...
Source: Molecular Metabolism - February 19, 2020 Category: Endocrinology Source Type: research

Obesity-induced reduced expression of the lncRNA ROIT impairs insulin transcription by downregulation of Nkx6.1 methylation
Conclusions/interpretationThese findings functionally suggest a novel link between obesity and beta cell dysfunction via ROIT. Elucidating a precise mechanism for the effect of obesity on lncRNA expression will broaden our understanding of the pathophysiological development of diabetes and facilitate the design of better tools for diabetes prevention and treatment.Data availabilityThe raw RNA sequencing data are available from the NCBI Gene Expression Omnibus (GEO series accession number GSE139991).
Source: Diabetologia - January 31, 2020 Category: Endocrinology Source Type: research

Identification of retinoid acid induced 16 as a novel androgen receptor target in prostate cancer cells
ConclusionsWe demonstrate for the first time that RAI16 is a direct target gene of AR. RAI16 may involved in cell growth of prostate cancer cells in response to AR signaling.
Source: Molecular and Cellular Endocrinology - January 31, 2020 Category: Endocrinology Source Type: research