Glucose treatment for cardiovascular patients

The question of the use of sugar in the treatment of cardiovascular patients arose around 1917-18. Recently, heightened interest has been shown again.

Placental 13C-DHA metabolism and relationship with maternal BMI, glycemia and birthweight

Background Fetal docosahexaenoic acid (DHA) supply relies on preferential transplacental transfer, which is regulated by placental DHA lipid metabolism. Maternal hyperglycemia and obesity associate with higher birthweight and fetal DHA insufficiency but the role of placental DHA metabolism is unclear. Methods Explants from 17 term placenta were incubated with 13C-labeled DHA for 48 h, at 5 or 10 mmol/L glucose treatment, and the production of 17 individual newly synthesized 13C-DHA labeled lipids quantified by liquid chromatography mass spectrometry. Results Maternal BMI positively associated with 13C-DHA-labeled diacylglycerols, triacylglycerols, lysophospholipids, phosphatidylcholine and phosphatidylethanolamine plasmalogens, while maternal fasting glycemia positively associated with five 13C-DHA triacylglycerols. In turn, 13C-DHA-labeled phospholipids and triacylglycerols positively associated with birthweight centile. In-vitro glucose treatment increased most 13C-DHA-lipids, but decreased 13C-DHA phosphatidylethanolamine plasmalogens. However, with increasing maternal BMI, the magnitude of the glucose treatment induced increase in 13C-DHA phosphatidylcholine and 13C-DHA lysophospholipids was curtailed, with further decline in 13C-DHA phosphatidylethanolamine plasmalogens. Conversely, with increasing birthweight centile glucose treatment induced increases in 13C-DHA triacylglycerols were exaggerated, while glucose treatment induced decreases in 13C-DHA phosphatidylethanolamine plasmalogens were diminished. Conclusions Maternal BMI and glycemia increased the production of different placental DHA lipids implying impact on different metabolic pathways. Glucose-induced elevation in placental DHA metabolism is moderated with higher maternal BMI. In turn, findings of associations between many DHA lipids with birthweight suggest that BMI and glycemia promote fetal growth partly through changes in placental DHA metabolism.

High glucose treatment promotes extracellular matrix proteome remodeling in Müller glial cells

Background The underlying pathomechanisms in diabetic retinopathy (DR) remain incompletely understood. The aim of this study was to add to the current knowledge about the particular role of retinal Müller glial cells (RMG) in the initial processes of DR. Methods Applying a quantitative proteomic workflow, we investigated changes of primary porcine RMG under short term high glucose treatment as well as glycolysis inhibition treatment. Results We revealed significant changes in RMG proteome primarily in proteins building the extracellular matrix (ECM) indicating fundamental remodeling processes of ECM as novel rapid response to high glucose treatment. Among others, Osteopontin (SPP1) as well as its interacting integrins were significantly downregulated and organotypic retinal explant culture confirmed the selective loss of SPP1 in RMG upon treatment. Since SPP1 in the retina has been described neuroprotective for photoreceptors and functions against experimentally induced cell swelling, it’s rapid loss under diabetic conditions may point to a direct involvement of RMG to the early neurodegenerative processes driving DR. Data are available via ProteomeXchange with identifier PXD015879.

High Glucose Causes Distinct Expression Patterns of Primary Human Skin Cells by RNA Sequencing

Diabetes-related skin problems represent the most common long-term complications in diabetes mellitus patients. These complications, which include diabetic dermopathy, diabetic blisters, necrobiosis lipoidica diabeticorum, and eruptive xanthomatosis, may dramatically impair patients’ quality of life and cause long-lasting disability. However, the cellular and molecular mechanisms linking diabetes-related hyperglycemia and skin complications are still incompletely understood. To assess the role of the various skin-cell types in hyperglycemia-induced skin disorders, we performed RNA sequencing-based transcriptome analysis, measuring gene expression patterns in biological replicates in normal- and high glucose-stimulated skin cells. Three primary human skin-cell types were examined, i.e., epidermal keratinocytes, dermal fibroblasts, and dermal microvascular endothelial cells. For each separate cell type, we identified gene expression. Comparing gene abundances and expression levels revealed that transcription profiles exhibit distinct patterns in the three skin-cell types exposed to normal (i.e., physiological) glucose treatment and high (i.e., supraphysiological) glucose treatment. The obtained data indicate that high glucose induced differential gene expression and distinct activity patterns in signaling pathways in each skin-cell type. We are adding these data to the public database in the hope that they will facilitate future studies to develop novel targeted interventions for diabetic skin complications.

Upregulation of miRNA-23a-3p rescues high glucose-induced cell apoptosis and proliferation inhibition in cardiomyocytes

Maternal hyperglycemia potentially inhibits the development of the fetal heart by suppressing cardiomyocyte proliferation and promoting apoptosis. Different studies have indicated that miRNAs are key regulators of cardiomyocyte proliferation, differentiation, and apoptosis and play a protective role in a variety of cardiovascular diseases. However, the biological function of miRNA-23a in hyperglycemia-related cardiomyocyte injury is not fully understood. The present study investigated the effect of miRNA-23a-3p on cell proliferation and apoptosis in a myocardial injury model induced by high glucose. H9c2 cardiomyocytes were exposed to high glucose to establish an in vitro myocardial injury model and then transfected with miRNA-23a-3p mimics. After miRNA-23a-3p transfection, lens-free microscopy was used to dynamically monitor cell numbers and confluence and calculate the cell cycle duration. CCK-8 and EdU incorporation assays were performed to detect cell proliferation. Flow cytometry was used to measured cell apoptosis. Upregulation of miRNA-23a-3p significantly alleviated high glucose-induced cell apoptosis and cell proliferation inhibition (p < 0.01 and p < 0.0001, respectively). The cell cycle of the miRNA-23a-3p mimics group was significantly shorter than that of the negative control group (p < 0.01). The expression of cell cycle–activating and apoptosis inhibition-associated factors Ccna2, Ccne1, and Bcl-2 was downregulated by high glucose and upregulated by miRNA-23a-3p overexpression in high glucose-injured H9c2 cells. miRNA-23a-3p mimics transfection before high glucose treatment had a significantly greater benefit than transfection after high glucose treatment (p < 0.0001), and the rescue effect of miRNA-23a-3p increased as the concentration increased. This study suggests that miRNA-23a-3p exerted a dose- and time-dependent protective effect on high glucose-induced H9c2 cardiomyocyte injury.