Altered blood-brain barrier (BBB) permeability may contribute to pathogenesis of diabetes-related central nervous system disorders. Considering the presence of glycated insulin in plasma of type 2 diabetic patients, we hypothesized that glycated insulin could induce changes in paracellular permeability in BBB. Therefore, the authors decided to study the effect of glycated insulin on paracellular permeability in a BBB model and the change induced in insulin conformation upon glycation. In this study, the structural modification was examined by fluorescence and circular dichroism spectroscopies and dynamic light scattering. Cell proliferation and production of ROS in astrocytes and HUVEC cells were analyzed by MTT and spectrofluorometric assays, respectively. Apoptosis induction was determined and confirmed by flow cytometry and western blot analyses, respectively. The permeability was measured Lucifer yellow and FITC-Dextran. According to our results, glycated insulin presented altered conformation and more exposed hydrophobic patches than insulin. Formation of oligomeric species and advanced glycated end products (AGEs) were determined. Lower cell viability, higher apoptosis, and more ROS were detected upon treatment of cells with glycated insulin. Finally, glycated insulin led to increased Lucifer yellow and FITC-dextran transportation across the BBB model which could result from ROS producing and apoptosis-inducing activities of AGE-insulin.

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.abb.2018.02.004DOI Listing

Publication Analysis

Top Keywords

glycated insulin
28
glycated
8
blood-brain barrier
8
insulin
8
paracellular permeability
8
permeability bbb
8
bbb model
8
lucifer yellow
8
yellow fitc-dextran
8
permeability
5

Similar Publications

Glycation restrains open-closed conformation of Insulin.

Comput Biol Chem

February 2023

Molecular Biophysics Lab, School of Chemical and Biotechnology, SASTRA Deemed to be University, Thanjavur 613401, Tamilnadu, India. Electronic address:

In hyperglycemic conditions, the level of reactive dicarbonyl metabolites concentration is found to be high, which plays a significant role in protein glycation. Despite decades of research, the effect of methylglyoxal on the structure and function of insulin is still unknown. Through a shift in conformation at the B-chain C-terminal (BT-CT) hinge from an "open" to a "wide-open" conformation, insulin binds to the receptor and activates the signal cascade.

View Article and Find Full Text PDF

Behavior of Regular Insulin in a Parenteral Nutrition Admixture: Validation of an LC/MS-MS Assay and the In Vitro Evaluation of Insulin Glycation.

Pharmaceutics

May 2022

Univ. Lille, CHU Lille, ULR 7365-GRITA-Groupe de Recherche sur les formes Injectables et les Technologies Associées, F-59000 Lille, France.

Parenteral-nutrition (PN)-induced hyperglycemia increases morbidity and mortality and must be treated with insulin. Unfortunately, the addition of insulin to a ternary PN admixture leads to a rapid decrease in insulin content. Our study's objective was to determine the mechanistic basis of insulin's disappearance.

View Article and Find Full Text PDF

Optimising insulin aspart practices in a neonatal intensive care unit: a clinical and pharmaco-technical study.

Eur J Pediatr

September 2021

ULR 7365 - GRITA - Groupe de Recherche sur les formes Injectables et les Technologies Associées, University of Lille, CHU Lille, F-59000, Lille, France.

Neonatal hyperglycaemia is frequent and requires insulin therapy. To resolve the difficulties encountered by paediatricians in stabilising glycaemia, the preparation and administration of insulin aspart were assessed and optimised. After high-performance liquid chromatography (HPLC-UV) assessment of insulin aspart preparations made according to the old protocol, a new protocol was drawn up.

View Article and Find Full Text PDF

Molecular investigation of glycated insulin-induced insulin resistance via insulin signaling and AGE-RAGE axis.

Biochim Biophys Acta Mol Basis Dis

February 2021

Biochemical Sciences Division, CSIR-National Chemical Laboratory, Pune-411008, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad-201002, India. Electronic address:

Hyperglycemic condition in diabetes promotes glycation of various plasma proteins including insulin. Glycation of insulin has been reported to reduce its biological activity. Reduced biological activity of glycated insulin could be either due to reduced affinity for the insulin receptor and impaired insulin signaling, or it can act as a ligand for the receptor for advanced glycation end products (RAGE) and activates oxidative stress and pro-inflammatory pathways leading to insulin resistance.

View Article and Find Full Text PDF

Both amyloid-β (Aβ) and insulin are amyloidogenic peptides, and they play a critical role in Alzheimer's disease (AD) and type-2 diabetes (T2D). Misfolded or aggregated Aβ and glycated insulin are commonly found in AD and T2D patients, respectively, and exhibit neurotoxicity and oxidative stress. The present study examined the anti-Aβ aggregation and anti-insulin glycation activities of five phlorotannins isolated from .

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!