FK506-Binding Protein 2 Participates in Proinsulin Folding.

Apart from chaperoning, disulfide bond formation, and downstream processing, the molecular sequence of proinsulin folding is not completely understood. Proinsulin requires proline isomerization for correct folding. Since FK506-binding protein 2 (FKBP2) is an ER-resident proline isomerase, we hypothesized that FKBP2 contributes to proinsulin folding. We found that FKBP2 co-immunoprecipitated with proinsulin and its chaperone GRP94 and that inhibition of FKBP2 expression increased proinsulin turnover with reduced intracellular proinsulin and insulin levels. This phenotype was accompanied by an increased proinsulin secretion and the formation of proinsulin high-molecular-weight complexes, a sign of proinsulin misfolding. FKBP2 knockout in pancreatic ß-cells increased apoptosis without detectable up-regulation of ER stress response genes. Interestingly, FKBP2 mRNA was overexpressed in ß-cells from pancreatic islets of T2D patients. Based on molecular modeling and an in vitro enzymatic assay, we suggest that proline at position 28 of the proinsulin B-chain (P28) is the substrate of FKBP2's isomerization activity. We propose that this isomerization step catalyzed by FKBP2 is an essential sequence required for correct proinsulin folding.

Diabetes and SARS-CoV-2-Is There a Mutual Connection?

SARS-CoV-2, a newly emerged virus described for the first time in late 2019, affects multiple organs in humans, including the pancreas. Here, we present the bilateral link between the pathophysiology of diabetes and COVID-19, with diabetes being COVID-19 comorbidity, and a complication of SARS-CoV-2 infection. Analysis of clinical data indicates that patients with chronic conditions like diabetes are at increased risk of severe COVID-19, hospitalization, ICU admission, and death compared to the healthy subjects. Further, we show that SARS-CoV-2 infection might be also associated with the development of new-onset diabetes and diabetic ketoacidosis. We then discuss the options for studying SARS-CoV-2 infection in pancreatic settings, including the use of human pluripotent stem cell-derived pancreatic organoids. Further, we review the presence of SARS-CoV-2 receptors in different pancreatic cell types and the infection efficiency based on pancreatic sections from COVID-19 patients and primary human islet in vitro studies. Finally, we discuss the impact of SARS-CoV-2 infection on human pancreatic cell homeostasis, focusing on ß-cells.

Assessment of the Effectiveness of Rehabilitation after Total Knee Replacement Surgery Using Sample Entropy and Classical Measures of Body Balance.

Exercises in virtual reality (VR) have recently become a popular form of rehabilitation and are reported to be more effective than a standard rehabilitation protocol alone. The aim of this study was to assess the efficacy of adjunct VR training in improving postural control in patients after total knee replacement surgery (TKR). Forty-two patients within 7-14 days of TKR were enrolled and divided into a VR group and a control group (C). The C group underwent standard postoperative rehabilitation. The VR group additionally attended twelve 30-min exercise sessions using the Virtual Balance Clinic prototype system. Balance was assessed on the AMTI plate in bipedal standing with and without visual feedback before and after the four-week rehabilitation. Linear measures and sample entropy of CoP data were analyzed. After four weeks of rehabilitation, a significant reduction in parameters in the sagittal plane and ellipse area was noted while the eyes remained open. Regression analysis showed that sample entropy depended on sex, body weight, visual feedback and age. Based on the sample entropy results, it was concluded that the complexity of the body reaction had not improved. The standing-with-eyes-closed test activates automatic balance mechanisms and offers better possibilities as a diagnostic tool.