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Aims: Chronic hyperglycemia triggers overproduction of AKR1B1 (aldo-keto reductase family 1 member B) and receptor for advanced glycation end product (RAGE), which causes epithelial-mesenchymal transition (EMT) in the lens epithelial cells (LECs) of diabetic mellitus (DM) cataracts. However, it is unclear whether EMT in LECs is related to abnormal increase of SGLT2. Sodium glucose cotransporter 2 (SGLT2) inhibitor, also known as dapagliflozin (Dapa) can be used to treat diabetes. Here, we examined how Dapa or nano eye-drops (DapaN) reduce EMT in LECs of DM cataracts. The nano eye-drop provides an ophthalmic treatment that suppressed diabetic cataract progression and improved potency with reduced side effects., Main Methods: SD rats were injected with streptozocin (STZ) (65 mg/kg, ip), nano-Dapa drops (0.456 mg/10 ml/eye) or Dapa (1.2 mg/kg/day) treatment for 6-12 weeks. Immunofluorescence staining was used for protein quantification of RAGE, SGLT2, N-cadherin and E-cadherin in the LECs of rats., Key Findings: In this study, Dapa applies nanotechnology-based delivery system and it contains polyvinylpyrrolidone (PVP) and HPBCD. Dapa showed therapeutic effect on DM cataracts, wherein it targeted EMT biomarker, E-cadherin. The nano-Dapa drops or oral Dapa inhibited SGLT2, suppressed AKR1B1 expression, decreased AcSOD2- and RAGE-induced EMT in diabetic cataracts. Our findings suggest that nanotechnology-based Dapa eye drops (Dapa-PVP-HPBCD) can effectively improve solubility of Dapa in aqueous solution., Significance: Taken together, results suggest that the SGLT2-mediated DM cataract therapy may involve the AKR1B1-RAGE-AcSOD2-EMT pathway. The nano eye drops and Dapa show potential beneficial effects for cataract prevention. This study conveys new insights into cataract treatment and supplementation of nano-Dapa drops shows promising result in preventing diabetic cataracts., Competing Interests: Declaration of competing interest The authors declared no competing financial interest., (Copyright © 2023. Published by Elsevier Inc.)

Background: Several studies have suggested mechanisms whereby excessive fructose intake increases blood pressure (BP). Glucose transporter 5 (GLUT5) is a fructose transporter expressed on enterocytes, and its involvement in the nucleus tractus solitarius (NTS)-modulated increase in BP following fructose intake remains unclear., Objectives: Herein, we investigated whether NTS Glut5 knockdown (KD) can alleviate fructose-induced hypertension in rat models., Methods: Male Wistar-Kyoto rats (6-8 weeks old; average weight: 230 g) were randomly assigned into 4 groups [control (Con), fructose (Fru), fructose + scrambled (Fru + S), and Fru +  KD]. The Con group rats had ad libitum access to regular water, and the other 3 groups were provided 10% fructose water ad libitum for 4 weeks (2 weeks before lentiviral transfection in the Fru + S and Fru + KD groups). Glut5 short hairpin RNA was delivered into the NTS of rats using a lentivirus system. Fructose-induced hypertension was assessed via the tail-cuff technique, a noninvasive blood pressure measurement approach. GLUT5-associated and other insulin signaling pathways in the NTS of rats were assessed using immunofluorescence and immunoblotting analyses. We evaluated between-group differences using the Mann-Whitney U test or Kruskal-Wallis 1-way ANOVA., Results: Compared with the Fru + S group, the Fru + KD group had reduced sympathetic nerve hyperactivity (48.8 ± 3.2 bursts/min; P < 0.05), improved central insulin signaling, upregulated protein kinase B (AKT; 3.0-fold) and neuronal NO synthase (nNOS; 2.78-fold) expression, and lowered BP (17 ± 1 mmHg, P < 0.05). Moreover, Glut5 KD restored signaling dependent on adenosine 5'-monophosphate-activated protein kinase and reduced fructose-induced oxidative stress 2.0-fold, and thus decreased NAD(P)H oxidase in p67-phox 1.9-fold within the NTS., Conclusions: Fructose-induced reactive oxygen species generates in the NTS of rats through GLUT5 and receptor for advanced glycation end products signaling, thus impairing the AKT-nNOS-NO signaling pathway and ultimately causing hypertension., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Society for Nutrition.)