PGRMC1 acts as a size-selective cargo receptor to drive ER-phagic clearance of mutant prohormones

The reticulon-3 (RTN3)-driven targeting complex promotes clearance of misfolded prohormones from the endoplasmic reticulum (ER) for lysosomal destruction by ER-phagy. Because RTN3 resides in the cytosolic leaflet of the ER bilayer, the mechanism of selecting misfolded prohormones as ER-phagy cargo on the luminal side of the ER membrane remains unknown. Here we identify the ER transmembrane protein PGRMC1 as an RTN3-binding partner. Via its luminal domain, PGRMC1 captures misfolded prohormones, targeting them for RTN3-dependent ER-phagy. PGRMC1 selects cargos that are smaller than the large size of other reported ER-phagy substrates. Cargos for PGRMC1 include mutant proinsulins that block secretion of wildtype proinsulin through dominant-negative interactions within the ER, causing insulin-deficiency. Chemical perturbation of PGRMC1 partially restores WT insulin storage by preventing ER-phagic degradation of WT and mutant proinsulin. Thus, PGRMC1 acts as a size-selective cargo receptor during RTN3-dependent ER-phagy, and is a potential therapeutic target for diabetes.

Impact of Video Technology on the Comprehension of Patients With First Insulin Injection and the Efficiency of Nurse Education

This study aims to compare the effectiveness of video and paper materials used for teach-back education on the first insulin injection for patients with diabetes. The study enrolled 110 patients hospitalized for diabetes who had received education on their first insulin injection in the endocrinology department. The patients were divided into an intervention group ( n = 55) and a control group ( n = 55) using convenience sampling. Video materials were employed for the teach-back education of the intervention group, while paper materials were employed for the teach-back education of the control group. We compared cases who answered correctly to the common parts (selection and management of injection devices, selection and rotation of injection sites, proper use of injection angles and pinching, insulin storage, injection-related complications and their prevention, selection of the correct needle length, and safe disposal of needles after use) for the first time, the number of educational sessions and total education duration between the two groups and employed the “ My View on Insulin” questionnaire to survey the two groups before and 28 days after the intervention. The intervention group had a shorter total education duration than the control group, a difference that was statistically significant ( p < .001). The intervention group had more advantages over the control group in terms of rotation education at the injection site ( p < .05). There was no statistically significant difference in the questionnaire scores between the two groups after the intervention ( p > .05); however, both groups scored significantly higher than before the intervention, a difference that was statistically significant ( p < .001). The teach-back method combined with video materials applied for educating patients on their first insulin injection could reduce the education duration by healthcare providers and improve the patients’ psychological insulin resistance. The key to successfully teaching patients to self-administer insulin, and allowing them to master the steps involved, is to focus on “why” rather than “what” to do.

Inside the Insulin Secretory Granule

The pancreatic β-cell is purpose-built for the production and secretion of insulin, the only hormone that can remove glucose from the bloodstream. Insulin is kept inside miniature membrane-bound storage compartments known as secretory granules (SGs), and these specialized organelles can readily fuse with the plasma membrane upon cellular stimulation to release insulin. Insulin is synthesized in the endoplasmic reticulum (ER) as a biologically inactive precursor, proinsulin, along with several other proteins that will also become members of the insulin SG. Their coordinated synthesis enables synchronized transit through the ER and Golgi apparatus for congregation at the trans-Golgi network, the initiating site of SG biogenesis. Here, proinsulin and its constituents enter the SG where conditions are optimized for proinsulin processing into insulin and subsequent insulin storage. A healthy β-cell is continually generating SGs to supply insulin in vast excess to what is secreted. Conversely, in type 2 diabetes (T2D), the inability of failing β-cells to secrete may be due to the limited biosynthesis of new insulin. Factors that drive the formation and maturation of SGs and thus the production of insulin are therefore critical for systemic glucose control. Here, we detail the formative hours of the insulin SG from the luminal perspective. We do this by mapping the journey of individual members of the SG as they contribute to its genesis.

Insulin Knowledge, Handling, and Storage among Diabetic Pilgrims during the Hajj Mass Gathering

Background. Diabetes is one of the most common underlying health conditions among Hajj pilgrims. Many diabetics manage their condition using insulin, which requires appropriate storage conditions to maintain its stability and effectiveness. We aimed to investigate insulin knowledge, storage, and handling among diabetic pilgrims during Hajj to identify specific areas for improvement. Method. Adult diabetic pilgrims from 22 countries were interviewed using a structured questionnaire during the 2019 Hajj. Results. The study enrolled 277 diabetic pilgrims with a mean age of 58.4 years ( SD = 10.4 , range: 20-83) and male : female ratio of 1.6 : 1. Most participants (86.4%) were literate and reported using insulin for a mean of 7.1 years ( SD = 5.3 , range: 1-23). Over 95% of pilgrims brought their insulin with them from their country of origin, where they also received most of their insulin storage information, mainly from physicians (77.8%) and pharmacists (59.6%). Pilgrims’ knowledge regarding insulin storage was just above average ( mean knowledge score = 0.51 ; SD = 0.23 ). Pilgrims who were literate and previously received education on insulin storage, those with a higher level of education, and those with a longer duration of insulin therapy, had significantly higher knowledge scores. Pilgrims’ storage and handling of their insulin during Hajj also varied depending on the stages of their pilgrimage journey. Conclusion. Inadequate knowledge and inappropriate practices regarding insulin handling and storage were identified among diabetic Hajj pilgrims, which could compromise the quality of insulin and lead to health hazards. Improving diabetic pilgrims’ knowledge of diabetes management, including insulin storage, will be beneficial during the pilgrimage and beyond.

Expedição Insulina: Avaliando o Acondicionamento da Insulina Durante Atividades de Lazer

A má conservação dos frascos e canetas de insulina, decorrentes da exposição a altas temperaturas, é uma das principais causas para um mau controle glicêmico. O estudo se propôs a realizar algumas pesquisas de campo com o objetivo de avaliar comparativamente as formas de acondicionamento da insulina, em relação a sua temperatura, durante as atividades de lazer. A pesquisa é do tipo descritivo-explicativa, realizada no período de maio de 2018 a abril de 2019. O estudo foi executado áreas de atividades de lazer. Foram realizadas medições de temperatura em frascos e canetas aplicadoras de insulina acondicionadas em recipientes diversos. Algumas formas de acondicionamento não conseguiram manter sempre o frasco da insulina em temperaturas ideais, quando expostas a temperaturas ambientes elevadas. Nas medições dos frascos de insulina, a bolsa térmica vazia ou com somente um gelo flexível, uso de isopor vazio e ausência de recipiente térmico foram medidas ineficazes para a conservação da medicação. Em relação às canetas aplicadoras medições mostraram que só o uso do estojo próprio, recomendado pelo fabricante, não conseguiu manter a insulina em temperatura recomendada. O conhecimento gerado nesta pesquisa tem o potencial de influenciar positivamente a vida dos usuários de insulina, pois impacta diretamente na forma como se realiza as atividades de lazer. Desta forma, com estas recomendações é possível promover melhor qualidade de vida aos portadores de diabetes mellitus usuários de insulina, já que poderão conciliar seu tratamento medicamentoso com suas atividades de lazer. Palavras-chave: Insulina. Transporte. Temperatura Elevada. Atividades de Lazer. Abstract The bad conservation of insulin vials and pens, due to exposure to high temperatures, is one of the main reasons for poor glycemic control. The study proposed to carry out some field research with the objective of comparatively evaluating the forms of insulin storage , in relation to its temperature, during leisure activities. The research is descriptive-explanatory type, carried out from May 2018 to April 2019. The study was conducted in leisure activities areas. Temperature measurements were made in vials and insulin pens conditioned in different containers. Some storage forms have not always managed to keep the insulin vial at ideal temperatures when exposed to elevated temperatures. In the measurements of insulin vials, the empty thermal bag or with only a flexible ice, the use of empty Styrofoam and the absence of thermal container were ineffective actions for the medication conservation. Regarding the applicator pens, measurements showed that only the use of the case itself, recommended by the manufacturer, failed to keep the insulin at the recommended temperature. The knowledge created in this research has the potential to positively influence the insulin users’ lives, as it directly impacts the way leisure activities are performed. Thus, with these recommendations it is possible to improve the quality of life of people with diabetes mellitus, insulin users, once they will be able to reconcile their drug treatment with their leisure activities. Keyword: Insulin. Transportation. Hot Temperature. Leisure Activities.