Notes

Very effective eliminating DEET by UV-LED irradiation from the presence of iron-containing coagulant.
The insulin-degrading enzyme (IDE) is a metalloendopeptidase with a high affinity for insulin. Human genetic polymorphisms in Ide have been linked to increased risk for T2DM. selleck In mice, hepatic Ide ablation causes glucose intolerance and insulin resistance when mice are fed a regular diet.
These studies were undertaken to further investigate its regulatory role in glucose homeostasis and insulin sensitivity in diet-induced obesity.

To this end, we have compared the metabolic effects of loss versus gain of IDE function in mice fed a high-fat diet (HFD).

We demonstrate that loss of IDE function in liver (L-IDE-KO mouse) exacerbates hyperinsulinemia and insulin resistance without changes in insulin clearance but in parallel to an increase in pancreatic β-cell function. Insulin resistance was associated with increased FoxO1 activation and a ~2-fold increase of GLUT2 protein levels in the liver of HFD-fed mice in response to an intraperitoneal injection of insulin. Conversely, gain of IDE function (adenoviral delivery) improves glucose tolerance and insulin sensitivity, in parallel to a reciprocal ~2-fold reduction in hepatic GLUT2 protein levels. Furthermore, in response to insulin, IDE co-immunoprecipitates with the insulin receptor in liver lysates of mice with adenoviral-mediated liver overexpression of IDE.

We conclude that IDE regulates hepatic insulin action and whole-body glucose metabolism in diet-induced obesity via insulin receptor levels.
We conclude that IDE regulates hepatic insulin action and whole-body glucose metabolism in diet-induced obesity via insulin receptor levels.
The transcription factor YY1 is an important regulator for metabolic homeostasis. Activating mutations in YY1 lead to tumorigenesis of pancreatic β-cells, however, the physiological functions of YY1 in β-cells are still unknown. Here, we investigated the effects of YY1 ablation on insulin secretion and glucose metabolism.

We established two models of β-cell-specific YY1 knockout mice. The glucose metabolic phenotypes, β-cell mass and β-cell functions were analyzed in the mouse models. Transmission electron microscopy was used to detect the ultrastructure of β-cells. The flow cytometry analysis, measurement of OCR and ROS were performed to investigate the mitochondrial function. Histological analysis, quantitative PCR and ChIP were performed to analyze the target genes of YY1 in β-cells.

Our results showed that loss of YY1 resulted in reduction of insulin production, β-cell mass and glucose tolerance in mice. Ablation of YY1 led to defective ATP production and mitochondrial ROS accumulation in pancreatic β-cells. The inactivation of YY1 impaired the activity of mitochondrial oxidative phosphorylation, induced mitochondrial dysfunction and diabetes in mouse models.

Our findings demonstrate that the transcriptional activity of YY1 is essential for the maintenance of mitochondrial functions and insulin secretion in β-cells.
Our findings demonstrate that the transcriptional activity of YY1 is essential for the maintenance of mitochondrial functions and insulin secretion in β-cells.
Fructose consumption increases risk factors for cardiometabolic disease. It is assumed that the effects of free sugars on risk factors are less potent because they contain less fructose. We compared the effects of consuming fructose, glucose or their combination, high fructose corn syrup (HFCS), on cardiometabolic risk factors.

Adults (18-40 years; BMI 18-35 kg/m
) participated in a parallel, double-blinded dietary intervention during which beverages sweetened with aspartame, glucose (25% of energy requirements (ereq)), fructose or HFCS (25% and 17.5% ereq) were consumed for two weeks. Groups were matched for sex, baseline BMI and plasma lipid/lipoprotein concentrations. 24-h serial blood samples were collected at baseline and at the end of intervention. Primary outcomes were 24-h triglyceride AUC, LDL-cholesterol (C), and apolipoprotein (apo)B. Interactions between fructose and glucose were assessed post hoc.

145 subjects (26.0 ± 5.8 years; body mass index 25.0 ± 3.7 kg/m
) completed the study. As ex two monosaccharides were co-ingested as HFCS. Thus, the effects of HFCS on lipoprotein risks factors are not solely mediated by the fructose content and it cannot be assumed that glucose is a benign component of HFCS. Our findings suggest that HFCS may be as harmful as isocaloric amounts of pure fructose and provide further support for the urgency to implement strategies to limit free sugar consumption.
A significant interaction between fructose and glucose contributed to increases of lipoprotein risk factors when the two monosaccharides were co-ingested as HFCS. Thus, the effects of HFCS on lipoprotein risks factors are not solely mediated by the fructose content and it cannot be assumed that glucose is a benign component of HFCS. Our findings suggest that HFCS may be as harmful as isocaloric amounts of pure fructose and provide further support for the urgency to implement strategies to limit free sugar consumption.
Treatment of children with classic congenital adrenal hyperplasia (CAH) is a difficult balance between hypercortisolism and hyperandrogenism. Biochemical monitoring of treatment is not well defined.

Cluster analysis of the urinary steroid metabolome obtained by targeted gas chromatography-mass spectrometry (GC-MS) for treatment monitoring of children with CAH.

We evaluated 24-h urinary steroid metabolome analyses of 109 prepubertal children aged 7.0 ± 1.6 years with classic CAH due to 21-hydroxylase deficiency treated with hydrocortisone and fludrocortisone. 24-h urinary steroid metabolite excretions were transformed into CAH-specific z-scores. Subjects were divided into groups (metabotypes) by k-means clustering algorithm. Urinary steroid metabolome and clinical data of patients of each metabotype were analyzed.

Four unique metabotypes were generated. Metabotype 1 (N = 21 (19%)) revealed adequate metabolic control with low cortisol metabolites (mean -0.57z) and suppressed androgen and 17α-hydroxyprogesterone (17OHP) metabolites (-0.
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