silicon and Diabetes-Mellitus--Type-2

Diabetic kidney disease (DKD) is the most common microvascular complication of diabetes, and there is an urgent need to discover reliable biomarkers for early diagnosis. Here, we established an effective urine multi-omics platform and integrated metabolomics and peptidomics to investigate the biological changes during DKD pathogenesis.

Topics: Diabetes Mellitus, Type 2; Diabetic Nephropathies; Humans; Metabolomics; Peptides; Silicon; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization

Hypercholesterolemia increases the risk of mortality in type 2 diabetes mellitus (T2DM), especially in the late-stage. Consumption of bioactive compounds as functional ingredients would help achieve therapeutic goals for cholesterolemia. Silicon has demonstrated a hypocholesterolemic effect and the ability to reduce fat digestion. However, it is unclear whether silicon exerts such effect in late-stage T2DM (LD) and the intestinal mechanisms involved.. Three groups of eight rats were included: early-stage T2DM control (ED), LD, and the LD group treated with silicon (LD-Si) once the rats were diabetic. Morphological alterations of the duodenal mucosa, and levels of markers involve in cholesterol absorption and excretion, beside cholesterolemia, and fecal excretion were assayed. Silicon included as a functional ingredient significantly reduces cholesterolemia in part due to: 1) reducing cholesterol intestinal absorption by decreasing the absorptive area and Acetyl-Coenzyme A acetyltransferase-2 (ACAT2) levels; and 2) increasing cholesterol excretion to the lumen by induction of the liver X receptor (LXR) and consequent increase of adenosine triphosphate-binding cassette transporter (ABCG5/8).. These results provide insight into the intestinal molecular mechanisms by which silicon reduces cholesterolemia and highlights the efficacy of the consumption of silicon-enriched functional foods in late-stage T2DM.

Topics: Animals; ATP Binding Cassette Transporter, Subfamily G, Member 5; ATP-Binding Cassette Transporters; Cholesterol; Diabetes Mellitus, Type 2; Lipoproteins; Liver; Rats; Silicon

Metabolites in the body fluid are becoming a rich source of disease biomarkers. Developing an effective and high throughput detection and analysis platform of metabolites is of great importance for potential biomarker discovery and validation. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) has been successfully applied in rapid biomolecules detection in large scale. However, non-negligible background interference in low molecule-weight region still constitutes a main challenge even though various nanomaterials have been developed as an alternative to traditional organic matrix. In this work, a novel composite chip, silicon nanowires loaded with fluorinated ethylene propylene (FEP@SiNWs) was fabricated. It can serve as an excellent substrate for nanostructure-initiator mass spectrometry (NIMS) detection with ultra-low background noise in low molecular weight region (<500 Da). Ion desorption efficiency and internal energy transfer of FEP@SiNWs were studied using benzylpyridinium salt and tetraphenylboron salt as thermometer chemicals. The results indicated that a non-thermal desorption mechanism might be involved in the LDI process on FEP@SiNWs. Owing to the higher LDI efficiency and low background interference of this novel substrate, the metabolic fingerprint of complex bio-fluids, such as human saliva, can be sensitively and stably acquired. As a proof of concept, FEP@SiNWs chip was successfully used in the detection of salivary metabolites. With the assistance of multivariate analysis, 22 metabolic candidates (p < 0.05) which can discriminate type 2 diabetes mellitus (2-DM) and healthy volunteers were found and identified. The role of these feature metabolites in the metabolic pathway involved in 2-DM was confirmed by literature mining. This work demonstrates that FEP@SiNWs-based NIMS might be served as an efficient and high throughput platform for metabolic biomarker exploration and clinical diagnosis.

Topics: Diabetes Mellitus, Type 2; Humans; Lasers; Nanowires; Polymers; Silicon; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization

Glucagon-like peptide-1 (GLP-1), an incretin hormone, is used for type 2 diabetes mellitus (T2DM) treatment because of its ability to stimulate insulin secretion and release in a glucose-dependent manner. Despite of its potent insulinotropic effect, oral GLP-1 delivery is greatly limited by its instability in the gastrointestinal tract, poor absorption efficiency and rapid degradation by dipeptidylpeptidase-4 (DPP4) enzyme leading to a short half-life (~2min). Thus, a multistage dual-drug delivery nanosystem was developed to deliver GLP-1 and DPP4 inhibitor simultaneously. The system comprised of chitosan-modified porous silicon (CSUn) nanoparticles, which were coated by an enteric polymer, hydroxypropylmethylcellulose acetate succinate MF, using aerosol flow reactor technology. A non-obese T2DM rat model induced by co-administration of nicotinamide and streptozotocin was used to evaluate the in vivo efficacy of the nanosystem. The oral administration of H-CSUn nanoparticles resulted in 32% reduction in blood glucose levels and ~6.0-fold enhancement in pancreatic insulin content, as compared to the GLP-1+DPP4 inhibitor solution. Overall, these results present a promising system for oral co-delivery of GLP-1 and DPP4 inhibitor that could be further evaluated in a chronic diabetic study.

Topics: Administration, Oral; Animals; Blood Glucose; Chitosan; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Drug Therapy, Combination; Glucagon-Like Peptide 1; Intestine, Small; Methylcellulose; Nanocomposites; Nanoparticles; Rats, Wistar; Silicon