Duodenal SGLT-1 expression is increased in individuals with 1-hour postload hyperglycemia or IGT, as well as in subjects with T2DM, and it positively correlates with early postload glucose excursion.

No abstract

Background: Resilience is defined as the capacity to cope successfully with change or adversity. The aims of our study were to investigate levels of resilience in Italian healthcare professionals (HCPs) during the Coronavirus disease 2019 (COVID-19) pandemic and to identify potential predictors of resilience. Methods: We performed a web-based survey of HCPs (n = 1009) working in Italian hospitals during the COVID-19 pandemic. The survey contained a 14-item resilience scale (RS14) and questionnaires to evaluate depression and anxiety symptoms. Non-HCP individuals (n = 375) from the general population were used for comparison. Results: HCPs showed significantly lower resilience compared to the control group (p = 0.001). No significant differences were observed after stratification for geographical area, work setting, role, or suspected/confirmed diagnosis of COVID-19. In a linear regression analysis, RS14 was inversely correlated with depression (R2 = 0.227, p < 0.001) and anxiety (R2 = 0.117, p < 0.001) and directly correlated with age (R2 = 0.012, p < 0.001) but not with body mass index (BMI, R2 = 0.002, p = 0.213). In male HCPs, higher depression score (odds ratio (OR) 1.147, p < 0.001) or BMI (OR 1.136, p = 0.011) significantly predicted having low resilience. In female HCPs, higher depression score (OR 1.111, p < 0.0001) and working in a COVID-19 free setting (OR 2.308, p = 0.002) significantly predicted having low resilience. HCPs satisfied with personal protective equipment had higher levels of resilience (p < 0.010). Conclusions: Our findings suggest that resilience was lower in Italian HCPs than in the general population after the first COVID-19 wave. Specific factors can be identified, and targeted interventions may have an important role to foster resilience of HCPs.

Type 2 diabetes mellitus (T2DM) is a risk factor for cognitive impairment. Ranolazine, an anti-ischemic drug used in the treatment of angina pectoris, has been shown to possess hypoglycemic properties in pre-clinical and clinical studies. The aim of this study was to evaluate the effects of ranolazine on glucose metabolism and cognitive function in a T2DM model of Wistar rats. Diabetes was induced by a high fat diet (HFD) and streptozotocin (STZ). The control group received a normal caloric diet (NCD) and sodium citrate buffer. Metformin, an effective hypoglycemic drug, was employed as a positive control. Animals were divided into the following groups: HFD/STZ + Ranolazine, HFD/STZ + Metformin, HFD/STZ + Vehicle, NCD + Vehicle, NCD + Ranolazine, and NCD + Metformin. Rats received ranolazine (20 mg/kg), metformin (300 mg/kg), or water, for 8 weeks. At the end of the treatments, all animals underwent to an intraperitoneal glucose tolerance test (IPGTT) and behavioral tests, including passive avoidance, novel object recognition, forced swimming, and elevate plus maze tests. Interleukin-6 plasma levels in the six treatment groups were assessed by Elisa assay. Body mass composition was estimated by nuclear magnetic resonance (NMR). Glucose responsiveness significantly improved in the HFD/STZ + Ranolazine (p < 0.0001) and HFD/STZ + Metformin (p = 0.003) groups. There was a moderate effect on blood glucose levels in the NCD + Ranolazine and NCD + Metformin groups. Lean body mass was significantly increased in the HFD/STZ + Ranolazine and HFD/STZ + Metformin animals, compared to HFD/STZ + Vehicle animals. Ranolazine improved learning and long-term memory in HFD/STZ + Ranolazine compared to HFD/STZ + Vehicle (p < 0.001) and ameliorated the pro-inflammatory profile of diabetic mice. These results support the hypothesis of a protective effect of ranolazine against cognitive decline caused by T2DM.

High levels of uric acid (UA) are associated with type-2 diabetes and cardiovascular disease. Recent pieces of evidence attributed to UA a causative role in the appearance of diabetes and vascular damage. However, the molecular mechanisms by which UA induces these alterations have not been completely elucidated so far. Among the mechanisms underlying insulin resistance, it was reported the role of a transmembrane glycoprotein, named either ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) or plasma cell antigen 1, which is able to inhibit the function of insulin receptor (IR) and it is overexpressed in insulin-resistant subjects. In keeping with this, we stimulated human umbilical vein endothelial cells (HUVECs) with insulin and UA to investigate the effects of UA on insulin signaling pathway, testing the hypothesis that UA can interfere with insulin signaling by the activation of ENPP1. Cultures of HUVECs were stimulated with insulin, UA and the urate transporter SLC22A12 (URAT1) inhibitor probenecid. Akt and endothelial nitric oxide synthase (eNOS) phosphorylation levels were investigated by immunoblotting. ENPP1 binding to IR and its tyrosine phosphorylation levels were tested by immunoprecipitation and immunoblotting. UA inhibited insulin-induced Akt/eNOS axis. Moreover, UA induced ENPP1 binding to IR that resulted in an impairment of insulin signaling cascade. Probenecid reverted UA effects, suggesting that UA intracellular uptake is required for its action. In endothelial cells, UA directly interferes with insulin signaling pathway at receptor level, through ENPP1 recruitment. This evidence suggests a new molecular model of UA-induced insulin resistance and vascular damage.