Roles of Voltage-Gated Tetrodotoxin-Sensitive Sodium Channels NaV1.3 and NaV1.7 in Diabetes and Painful Diabetic Neuropathy

Diabetes mellitus (DM) is a common chronic medical problem worldwide; one of its complications is painful peripheral neuropathy, which can substantially erode quality of life and increase the cost of management. Despite its clinical importance, the pathogenesis of painful diabetic neuropathy (PDN) is complex and incompletely understood. Voltage-gated sodium channels (VGSCs) link many physiological processes to electrical activity by controlling action potentials in all types of excitable cells. Two isoforms of VGSCs, Na_V1.3 and Na_V1.7, which are encoded by the sodium voltage-gated channel alpha subunit 3 and 9 (Scn3A and Scn9A) genes, respectively, have been identified in both peripheral nociceptive neurons of dorsal root ganglion (DRG) and pancreatic islet cells. Recent advances in our understanding of tetrodotoxin-sensitive (TTX-S) sodium channels Na_V1.3 and Na_V1.7 lead to the rational doubt about the cause–effect relation between diabetes and painful neuropathy. In this review, we summarize the roles of Na_V1.3 and Na_V1.7 in islet cells and DRG neurons, discuss the link between DM and painful neuropathy, and present a model, which may provide a starting point for further studies aimed at identifying the mechanisms underlying diabetes and painful neuropathy.     

Analysis of specific lipid metabolites in cord blood of patients with gestational diabetes mellitus

This work aimed to clarify the interaction between the fetus and pregnant patients with gestational diabetes mellitus (GDM), the lipid metabolomics analysis of the fetal umbilical cord blood of GDM patients and normal pregnant women were performed to screen out the specific lipid metabolites for pathogenesis of GDM. From 2019–2020, 21 patients with GDM and 22 normal pregnant women were enrolled in Hexian Memorial Hospital, Panyu District, Guangzhou. The general information such as weight, height, age, body mass index (BMI) before pregnancy were analyzed. Non-targeted metabonomic detection and analysis were performed in umbilical cord plasma using LC-MS method. The age, BMI, delivery methods, and infant weight were different between GDM and control. There were 167 lipid metabolites in umbilical cord blood associated with GDM. Among them, 158 upregulated and 9 downregulated in GDM. There were 13 dysregulated metabolites with C < 30, including Lyso-phosphatidyl-colines LPC 16:0, 18:2, 18:1, 18:0, 20:4 and 22:6, glycerophosphocholines PC O-16:1, oleoylcarnitine CAR 18:2 and 18:1, dihexosylceramides Hex2Cer 13:0;2O, phosphatidylethanolamine PE O-22:6_2:0 and PE O-22:6_3:0 and sphingomyelin SM 8:0; 2O/11:0. Those metabolites were associated with glycerophospholipid metabolism and sphingolipid metabolism. Therefore, Lyso-phosphatidyl-colines, glycerophosphocholines, oleoylcarnitine, dihexosylceramides, phosphatidylethanolamine, and sphingomyelin were main lipid metabolites of GDM, which might be used for diagnosis and treatment of GDM.     

A feedback glucose control strategy for type II diabetes mellitus based on fuzzy logic

Most patients with severe Type II diabetes mellitus, characterised by both insulin resistance and β‐cell failure, eventually require insulin therapy. According to the nonlinear dynamics of homeostasis of blood glucose, proportional‐integral (PI) controller, modified by penalising the feedback error using a fuzzy inference system has been developed to maintain normoglycaemia in a simulated patient using a closed‐loop insulin infusion pump. The simulation employs a compartment model proposed by Vahidi et al. [Vahidi et al., Biochem. Eng. J. 2011, 55(1), 7–16]. The results demonstrate that the fuzzy‐based PI controller is superior to a conventional PI controller for the regulation of blood glucose by insulin infusion for Type II diabetic patients. © 2012 Canadian Society for Chemical Engineering     

Glycemic Variability and Oxidative Stress: A Link between Diabetes and Cardiovascular Disease?

Diabetes is associated with a two to three-fold increase in risk of cardiovascular disease. However, intensive glucose-lowering therapy aiming at reducing HbA1c to a near-normal level failed to suppress cardiovascular events in recent randomized controlled trials. HbA1c reflects average glucose level rather than glycemic variability. In in vivo and in vitro studies, glycemic variability has been shown to be associated with greater reactive oxygen species production and vascular damage, compared to chronic hyperglycemia. These findings suggest that management of glycemic variability may reduce cardiovascular disease in patients with diabetes; however, clinical studies have shown conflicting results. This review summarizes the current knowledge on glycemic variability and oxidative stress, and discusses the clinical implications.     

Mechanochemical preparation of kaempferol intermolecular complexes for enhancing the solubility and bioavailability

Abstract

In this study, complexes of kaempferol (KF) with polysaccharide arabinogalactan (AG) and disodium glycyrrhizinate (Na₂GA) were prepared through mechanochemical technique to improve the solubility and bioavailability of KF. The physicochemical properties and the interactions of KF with AG/Na₂GA were investigated through dissolution, SEM, XRD, and DSC studies. The reduction of particle sizes and destruction of crystal forms revealed the formation of solid dispersion which may have assisted the dissolution of the drug. The accelerated stability study showed higher stability for KF–Na₂GA complex. In vivo pharmacokinetic study was performed to observe the plasma drug concentrations for KF complexes. Mechanochemical complexation of KF with AG/Na₂GA improved the pharmacological activity as evident by the inhibitory potential of the complexes towards carbohydrate metabolic enzymes. In vivo studies were performed in STZ-induced diabetic mice, where the group treated with KF–AG complex showed better liver and kidney function and lower blood glucose levels than pure KF. Therefore, mechanochemical complexes of KF with polysaccharide or glycyrrhizate may serve as a promising formulation for the treatment of diabetes.     

Association of Serum Uric Acid Concentration with Diabetic Retinopathy and Albuminuria in Taiwanese Patients with Type 2 Diabetes Mellitus

Patients with type 2 diabetes mellitus (DM) may experience chronic microvascular complications such as diabetic retinopathy (DR) and diabetic nephropathy (DN) during their lifetime. In clinical studies, serum uric acid concentration has been found to be associated with DR and DN. The goal of this study was to evaluate the relationship between the increases in serum uric acid level and the severity of DR and albuminuria in Taiwanese patients with type 2 DM. We recorded serum uric acid concentration, the severity of DR, and the severity of albuminuria by calculating urinary albumin-to-creatinine ratio (UACR) in 385 patients with type 2 DM. In multivariate logistic regression analysis, a high uric acid concentration was a risk factor for albuminuria (odds ratio (OR), 1.227; 95% confidence interval (CI) = 1.015–1.482; p = 0.034) and DR (OR, 1.264; 95% CI = 1.084–1.473; p = 0.003). We also demonstrated that there was a higher concentration of serum uric acid in the patients with more severe albuminuria and DR. In conclusion, an increased serum uric acid level was significantly correlated with the severity of albuminuria and DR in Taiwanese patients with type 2 DM.