Liver-specific ablation of insulin-degrading enzyme causes hepatic insulin resistance and glucose intolerance, without affecting insulin clearance in mice

The study was partially presented as a poster in the 53rd Annual Meeting of the European Association for the Study of Diabetes, Lisbon 2017.The role of insulin-degrading enzyme (IDE), a metalloprotease with high affinity for insulin, in insulin clearance remains poorly understood. OBJECTIVE: This study aimed to clarify whether IDE is a major mediator of insulin clearance, and to define its role in the etiology of hepatic insulin resistance.[Methods] We generated mice with liver-specific deletion of Ide (L-IDE-KO) and assessed insulin clearance and action.[Results] L-IDE-KO mice exhibited higher (~20%) fasting and non-fasting plasma glucose levels, glucose intolerance and insulin resistance. This phenotype was associated with ~30% lower plasma membrane insulin receptor levels in liver, as well as ~55% reduction in insulin-stimulated phosphorylation of the insulin receptor, and its downstream signaling molecules, AKT1 and AKT2 (reduced by ~40%). In addition, FoxO1 was aberrantly distributed in cellular nuclei, in parallel with up-regulation of the gluconeogenic genes Pck1 and G6pc. Surprisingly, L-IDE-KO mice showed similar plasma insulin levels and hepatic insulin clearance as control mice, despite reduced phosphorylation of the carcinoembryonic antigen-related cell adhesion molecule 1, which upon its insulin-stimulated phosphorylation, promotes receptor-mediated insulin uptake to be degraded.[Conclusion] IDE is not a rate-limiting regulator of plasma insulin levels in vivo.This work was supported by grants from the Ministerio de Economía, Industria y Competitividad: SAF2014-58702-C2-1-R and SAF2016-77871-C2-1-R to ICC; SAF2014-58702-C2-2-R and SAF2016-77871-C2-2-R to GP; supported by the EFSD European Research Programme on New Targets for Type 2 Diabetes supported by an educational research grant from MSD to ICC and GP; the National Institutes of Health: R01-DK054254, R01-DK083850 and RO1-HL-112248 to SMN, and R01-GM115617 to MAL; and the American Diabetes Association: Career Development Award 7-11-CD-13 to MAL.Peer reviewe

Efficacy and safety of anti-TNF therapy in elderly patients with inflammatory bowel disease

The general increased life expectancy is reflected in the age of patients with inflammatory bowel disease (IBD). The knowledge about efficacy and safety of anti-tumour necrosis factor (TNF) therapy in elderly is scarce and conflicting.status: publishe

Rapid Home-Based Human Immunodeficiency Virus Testing to Reduce Costs in a Large Tuberculosis Cohort Study

To reduce costs in a large tuberculosis household contact cohort study in Lima, Peru, we replaced laboratory-based human immunodeficiency virus (HIV) testing with home-based rapid HIV testing. We developed a protocol and training course to prepare staff for the new strategy; these included role-playing for home-based deployment of the Determine® HIV 1/2 Ag/Ac Combo HIV test. Although the rapid HIV test produced more false-positives, the overall cost per participant tested, refusal rate and time to confirmatory HIV testing were lower with the home-based rapid testing strategy compared to the original approach. Rapid testing could be used in similar research or routine care settings

First results of the BELCOMID study : Belgian cohort study of COVID-19 in Immune Mediated Inflammatory Diseases (IMID)

BACKGROUND: It has been suggested that 100% of SARS-CoV2 infections leads to development of specific IgG antibodies that remain detectable for a long period of time. Targeted Immune-Modulating Therapies (TIMT) such as anti-TNF, anti-interleukins and Janus Kinase inhibitors (JAKi) for treatment of Immune Mediated Inflammatory diseases (IMID) could theoretically interfere with cytokine storm and humoral immune response against COVID19. We investigate the seroprevalence of SARS-CoV2 IgG in relation to previous exposure to COVID19 and ongoing IMID treatment in a Belgian, real-life population of IMID patients. METHODS: A cross-disciplinary, prospective, observational cohort study was set up at two university hospitals. Between 17/12/2020 and 29/02/2021, all patients with IMIDs of the gut (Crohn’s disease (CD), ulcerative colitis (UC)), joints (rheumatoid arthritis, psoriatic arthritis, spondyloarthritis) and skin (psoriasis, hidradenitis suppurativa, atopic dermatitis) visiting the respective clinics were asked to participate. Both patients under conventional treatment and/or TIMT were included. Patients were asked to fill out an electronic survey (REDCap®, based on WHO-ISARIC) and blood samples were drawn for serology testing (SARS-CoV-2 IgG Abbott – Architect kit®). Statistical analyses were performed with SPSS26. RESULTS: In total 2166 IMID patients consented to take part. Of these, 1913 responded to the survey, including 218 dermatology patients, 415 rheumatology patients and 1217 IBD patients (64.7% CD, 34.3% UC, 1% undifferentiated colitis). There were 372 patients (19.5%) who reported having experienced symptoms suggestive of COVID19 (Fig. 1). Fatigue (61.3%), headache (48.1%), throat ache (46.9%) and dry cough (38.7%) were most frequent. Gastrointestinal symptoms such as diarrhoea or abdominal pain were present in less than 20.0% (Fig. 2). Ninety-six IMID patients (5.04%) had a positive SARS-CoV2 PCR test on nasal or throat swab. In 44/96 (45.8%) anti-SARS-CoV2 IgG seroconversion was confirmed. There was no significant difference in seroconversion rate between patients treated with TIMT compared to conventional therapy (P=0.192). Of the seroconverted group, 75.0% were treated with TIMT. The interval between reported positive PCR date and serology test date ranged from 3 to 24 weeks with a mean of 10 weeks. Of all survey responders, 25 were hospitalized for respiratory symptoms since 01/02/2020, six of these had positive SARS-CoV2 PCR. [Image: see text] [Image: see text] CONCLUSION: Prevalence of COVID19 symptoms and number of confirmed COVID19 cases by PCR in this cohort of IMID patients remain low regardless of treatment modality. There was no significant difference in SARS-CoV2 IgG seroconversion rate between TIMT or conventional treatment in patients with positive PCR

Clavigero. Comunidad de saberes, núm 4: Los derechos a la comunicación

Algunos compañeros del Capítulo Jalisco de la Asociación Mexicana de Derecho a la Información (AMEDI) explican brevemente qué son los derechos a la comunicación y por qué ha sido tan difícil hacerlos valer. A mayor conocimiento de ellos, será más factible exigir su cumplimiento