Protection by beta-Hydroxybutyric acid against insulin glycation, lipid peroxidation and microglial cell apoptosis

Abstract

BackgroundDiabetes mellitus is characterized jointly by hyperglycemia and hyperinsulinemia that make insulin more prone to be glycated and evolve insulin advanced glycation end products (Insulin- AGE). Here, we report the effect of beta-hydroxy butyrate (BHB) (the predominant ketone body) on the formation of insulin-AGE, insulin glycation derived liposomal lipid peroxidation and insulin-AGE toxicity in microglial cells.MethodsThe inhibitory effect of BHB was monitored as a result of insulin incubation in the presence of glucose or fructose using AGE-dependent fluorescence, Tyr fluorescence as well as anilinonaphthalenesulfonate (ANS) andthioflavin T (ThT) binding, and circular dichroism (CD) investigations. To study lipid peroxidation induced by insulin glycation, thiobarbituric acid (TBA) assay and thiobarbituric acid reactive substance (TBARS) monitoring were used. The effect of insulin–AGE on microglial viability was investigated by 3-(4, 5 dimethylthiazol-2-yl)—2, 5-diphenyltetrazoliumbromide (MTT) cell assay and Annexin V/propidium iodide (PI) staining.ResultsHere we are reporting the inhibitory effect of BHB on insulin glycation and generation of insulin-AGE as a possible explanation for insulin resistance. Moreover, the protective effect of BHB on consequential glycation derived liposomal lipid peroxidation as a causative event in microglial apoptosis is reported.ConclusionThe reduced insulin fibril formation, structural inertia to glycation involved conformational changes, anti-lipid peroxidation effect, and increasing microglia viability indicated the protective effect of BHB that disclose insight on the possible preventive effect of BHB on Alzheimer’s disease.

Associations between gut microbiota and Alzheimer’s disease, major depressive disorder, and schizophrenia

“…Considering the important roles of gut microbiotaderived metabolites in microbiota-host crosstalk in the brain function and behavior, we further chose key metabolites with available GWAS, including propionic acid, β-hydroxybutyric acid (BHB), serotonin, GABA, trimethylamine N-oxide (TMAO), betaine, choline, and carnitine. These gut microbial metabolites play crucial roles in maintaining a healthy neuropsychiatric function, and if dysregulated, potentially causally linked to neuropsychiatric disorders according to previous studies [3,24,25]. We searched PubMed for GWASs of the gut metabolites and leveraged summary-level data from a recent GWAS of the human metabolome conducted among 2076 participants of the Framingham Heart Study ( Table 1) [20].…”

Glucose Sensing for Diabetes Monitoring: Recent Developments

“…Diabetes mellitus is an incurable disease [ 1 ] resulting from an insufficiency of insulin in the body [ 2 ], causing elevated blood-glucose levels, known as hyperglycaemia, or reduced glucose concentrations, known as hypoglycaemia [ 3 , 4 ]. Insulin is a hormone which is synthesised and secreted from the pancreas to mediate metabolic reactions involving glucose [ 5 , 6 ].…”

Epimedium koreanum Extract and Its Flavonoids Reduced Atherosclerotic Risk via Suppressing Modification of Human HDL

“…Cleavage of these products is known to generate malondialdehyde (MDA). Measuring the formation of CD and MDA is the most commonly employed method to evaluate lipid peroxidation in vitro [31]. CD and MDA have been reportedly generated in substantially large amounts in copper-mediated oxidization of HDL [12,37].…”

“…Afterwards, HDL samples were dialyzed for 24 h at 4 °C against 10 mM phosphate buffer (pH 7.4). AGEs of HDL samples were determined by measuring the fluorescence intensity (Ex = 360 nm, Em = 460 nm) using a Synergy 2 multi-mode microplate reader (BioTek, VT, USA) [31].…”