RO1160367 / Roche - LARVOL DELTA

Adiponectin Enhances Hepatic Insulin Sensitivity in a Rat Model of Polycystic Ovary Syndrome: Role of PI3K/Akt/mTORC2 Pathway (ENDO 2024) - "Protein levels of insulin signaling markers including IRS1, p-IRS1 (Ser1101), PI3 kinase p110, Akt, p-Akt (Ser473), mTOR, p-mTOR (Ser2481) and mTORC2 regulatory protein Rictor were quantified in the liver by Western-blot... Our findings suggest that PEG-BHD1028 is a novel and effective therapeutic agent to attenuate hepatic IR in PCOS via activating PI3K/Akt/mTORC2 pathway. Significance: Targeting adiponectin signaling could be a novel and effective therapeutic approach to mitigate metabolic dysfunction in females with excess androgens.Unless otherwise noted, all abstracts presented at ENDO must not be released to the press or the public until the date and time of presentation. For oral presentations, the abstracts are embargoed until the session begins."

Preclinical • Diabetes • Endocrine Disorders • Genetic Disorders • Metabolic Disorders • Obesity • Polycystic Ovary Syndrome • IRS1

Phosphorylated and O-GlcNAc Modified IRS-1 (Ser1101) and -2 (Ser1149) Contribute to Human Diabetes type II. (PubMed, Protein Pept Lett) - "This study suggests a mechanism, which is controlled by posttranslational modifications, and may contribute to the pathogenesis of type II diabetes."

Journal • Diabetes • Genetic Disorders • Metabolic Disorders • Obesity • Type 2 Diabetes Mellitus • IRS2

HBx natural variants containing Ser-101 instead of Pro-101 evade ubiquitin-dependent proteasomal degradation by activating proteasomal activator 28 gamma expression. (PubMed, J Gen Virol) - "The self-amplifying ability of HBx variants containing Ser-101 via a positive feedback loop involving p53 and PA28γ was accurately reproduced in both a 1.2-mer HBV replicon and in vitro HBV infection systems, which also provided evidence for the stimulation of HBV replication by these HBx variants. In conclusion, the ability of HBx to upregulate PA28γ levels via p53 activation, in a Ser-101-dependent pathway, is critical for the stimulation of HBV replication."

Journal • Ataxia • Gastrointestinal Cancer • Hepatitis B • Hepatocellular Cancer • Immunology • Liver Cancer • Movement Disorders • Oncology • Solid Tumor • Targeted Protein Degradation

Exposure of decidualized HIESC to low oxygen tension and leucine deprivation results in increased IGFBP-1 phosphorylation and reduced IGF-I bioactivity. (PubMed) - Mol Cell Endocrinol - "...In contrast, significantly elevated phosphorylation was detected for pSer119, pSer98/pSer101 and pSer169/pSer174 sites. Immunoblotting and dual-immunofluorescence using phosphosite-specific IGFBP-1 antibodies further demonstrated increased IGFBP-1 phosphorylation in HIESC under both treatments which concomitantly reduced IGF-I bioactivity. These data support the hypothesis that down regulation of IGF-I signaling links decidual IGFBP-1 hyperphosphorylation to restricted fetal growth in placental insufficiency."

Journal • Biosimilar

Inhibition of mTOR, Activation of Amino Acid Response (AAR) and IGFBP-1 Hyperphosphorylation, in the Fetal Liver Precede the Development of IUGR in Baboons Following Maternal Nutrient Restriction (SRI 2018) - "...This model involves inhibition of mTOR signaling and activation of AAR signal transduction pathway in the fetal liver, which causes hyperphosphorylation of IGFBP-1 at Ser101, Ser169, and Ser119, ultimately resulting in decreased IGF-I bioavailability that contributes to reduced fetal growth... Inhibition of mTOR and activation of AAR signal transduction pathway in the fetal liver and increased IGFBP-1 abundance and phosphorylation in the fetal liver and umbilical cord plasma were observed at GD120, 45 days before IUGR is evident, in MNR baboons. These findings support our model that site-specific IGFBP-1 hyperphosphorylation, resulting in reduced IGF-I bioavailability, causes or contributes to the reduction in fetal growth in response to reduced nutrient availability."

Biosimilar