Glucose Load Following Prolonged Fasting Increases Oxidative Stress- Linked Response in Individuals With Diabetic Complications.

Objective: Prolonged catabolic states in type 2 diabetes (T2D), exacerbated by excess substrate flux and hyperglycemia, can challenge metabolic flexibility and antioxidative capacity. We investigated cellular responses to glucose load after prolonged fasting in T2D.

Research Design And Methods: Glucose-tolerant individuals (CON, n = 10) and individuals with T2D with (T2D+, n = 10) and without (T2D-, n = 10) diabetes complications underwent oral glucose tolerance test before and after a 5-day fasting-mimicking diet.

Accumulation of Non-Pathological Liver Fat Is Associated with the Loss of Glyoxalase I Activity in Humans.

The underlying molecular mechanisms for the development of non-alcoholic fatty liver (NAFL) and its progression to advanced liver diseases remain elusive. Glyoxalase 1 (Glo1) loss, leading to elevated methylglyoxal (MG) and dicarbonyl stress, has been implicated in various diseases, including obesity-related conditions. This study aimed to investigate changes in the glyoxalase system in individuals with non-pathological liver fat.

Non-cross-linking advanced glycation end products affect prohormone processing.

Advanced glycation end products (AGEs) are non-enzymatic post-translational modifications of amino acids and are associated with diabetic complications. One proposed pathomechanism is the impaired processing of AGE-modified proteins or peptides including prohormones. Two approaches were applied to investigate whether substrate modification with AGEs affects the processing of substrates like prohormones to the active hormones.

Impact of the -1T>C single-nucleotide polymorphism of the CD40 gene on the development of endothelial dysfunction in a pro-diabetic microenvironment.

Background And Aims: Hyperglycemia reinforces pro-inflammatory conditions that enhance CD40 expression in endothelial cells (EC). Thymine to cytosine transition (-1T > C) in the promoter of the CD40 gene (rs1883832) further increases the abundance of CD40 protein on the EC surface. This study examines potential associations of the -1T > C SNP of the CD40 gene with type 1 (T1D) or type 2 (T2D) diabetes.

Elevated markers of DNA damage and senescence are associated with the progression of albuminuria and restrictive lung disease in patients with type 2 diabetes.

Background: This study was conducted to investigate the cascade involving DNA damage, senescence, and senescence-associated secretory phenotype (SASP) in experimental diabetes and in a four-year follow-up study in patients with pre-diabetes and type 2 diabetes.

Methods: Kidney, lung, and liver were studied in 4 months diabetic db/db mice and age-matched controls for the presence of DNA damage and fibrosis. DNA damage (comet-tail-length and ɤH2Ax-positivity in white blood cells), urinary p21-excretion, and plasma IL-6 and TGF-β1 were determined from 115 healthy participants, 34 patients with pre-diabetes and 221 with type 2 diabetes.

Verification of sex- and age-specific reference intervals for 13 serum steroids determined by mass spectrometry: evaluation of an indirect statistical approach.

Objectives: Conventionally, reference intervals are established by direct methods, which require a well-characterized, obviously healthy study population. This elaborate approach is time consuming, costly and has rarely been applied to steroid hormones measured by mass spectrometry. In this feasibility study, we investigate whether indirect methods based on routine laboratory results can be used to verify reference intervals from external sources.

Six-Month Periodic Fasting in Patients With Type 2 Diabetes and Diabetic Nephropathy: A Proof-of-Concept Study.

Context: Novel fasting interventions have gained scientific and public attention. Periodic fasting has emerged as a dietary modification promoting beneficial effects on metabolic syndrome.

Objective: Assess whether periodic fasting reduces albuminuria and activates nephropathy-driven pathways.

Quantification of All-Trans Retinoic Acid by Liquid Chromatography-Tandem Mass Spectrometry and Association with Lipid Profile in Patients with Type 2 Diabetes.

Retinoic acids are vitamin A metabolites that have numerous essential functions in humans, and are also used as drugs to treat acne and acute promyelocytic leukemia. All-trans retinoic acid (RA) is the major occurring metabolite of retinoic acid in humans. This study provides a sensitive and specific liquid chromatography-tandem mass spectrometry approach in order to quantify RA in human plasma samples.

Michaelis-Menten Kinetics Measurements of Aldo-Keto Reductases for Various Substrates in Murine Tissue.

Aldo-keto reductases (AKRs) are responsible for the detoxification of harmful aldehydes. Due to the large number of isotypes, the physiological relevance of AKRs cannot be obtained using mRNA or protein quantification, but only through the use of enzymatic assays to demonstrate functionality. Here, we present a fast and simple protocol to determine the important Michaelis-Menten kinetics of AKRs, which includes various aldehyde substrates of interest such as 4-hydroxynonenal, methylglyoxal, and malondialdehyde.