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DNA methylation of the glucagon-like peptide 1 receptor (GLP1R) in human pancreatic islets.

Insulin secretion is enhanced upon the binding of Glucagon-like peptide-1 (GLP-1) to its receptor (GLP1R) in pancreatic β cells. Although a reduced expression of GLP1R in pancreatic islets from type 2 diabetic patients and hyperglycaemic rats has been established, it is still unknown if this is caused by differential DNA methylation of GLP1R in pancreatic islets of type 2 diabetic patients.

A rapid method for the separation of vitamin D and its metabolites by ultra-high performance supercritical fluid chromatography-mass spectrometry.

In this study, a new supercritical fluid chromatography-mass spectrometry (SFC-MS) method has been developed for the separation of nine vitamin D metabolites within less than eight minutes. This is the first study of analysis of vitamin D and its metabolites carried out by SFC-MS. Six columns of orthogonal selectivity were examined, and the best separation was obtained by using a 1-aminoanthracene

Increased IL-1 beta reactivity upon a glucose challenge in patients with deliberate self-harm

Objective: A disturbed glucose metabolism has been observed in patients with aggressive behaviour. Interleukin (IL)-1β is a pro-inflammatory cytokine that can induce hypoglycaemia, but has also been suggested to be involved in the generation of hostility and aggression. Our group has previously shown an altered glucose metabolism in patients with self-inflicted aggressive behaviour. We investigat

Letters of intent – ur praktisk synvinkel

I samband med kommersiella avtalsförhandlingar upprättas många olika förhandlingsdokument. Parterna kan skriva sekretessavtal, letters of intent, aktieägaravtal, anställningsavtal och överlåtelseavtal – för att nämna några. Under förhandlingarnas gång skickas många förhandlingsbud och åtskilliga avtalsförslag, avseende det slutliga överlåtelseavtalet, mellan parterna. Ett letter of intent bringaIn a contract negotiation a variety of negotiation documents are created. The parties may sign confidentiality agreements, letters of intent, shareholder agreements, employment agreements and transfer agreements – to name a few. During negotiations, many offers and proposals regarding the final transfer agreement are exchanged between the parties. A letter of intent brings order and clarity in a

Modulation of the sodium-chloride cotransporter by insulin in auditory cells : A potential link to diabetes-related hearing complications

Aim: While diabetes mellitus (types 1 and 2) is known to negatively impact vestibular and auditory function, the precise mechanisms underlying this effect are not fully understood. Building on our previous findings, which demonstrated the presence of insulin signaling components within the human saccule and identified the sodium transporter ENaC as a target for insulin signaling in HEI-OC1 auditor

Urine-normetanephrine, a predictor of mortality risk in patients with adrenal adenomas

Urine-metanephrines are used in the screening for pheochromocytomas in patients with adrenal incidentalomas, but their potential as markers for mortality in patients with adrenal adenomas has not been studied. A retrospective cohort study was designed to investigate if urine-metanephrines were associated with mortality in patients with adrenal adenomas. Participants where consecutively included be

Thyroid peroxidase antibodies and their role in predicting outcomes in Graves’ disease treatment

Introduction: Graves´ disease (GD) is the predominant cause of hyperthyroidism. Treatment options include antithyroid drugs (ATD), surgery, and radioactive iodine ablation (RI). Although thyroid peroxidase antibodies (anti-TPO) are prevalent in patients with GD, their role in driving relapse or hypothyroidism after treatment in patients with GD remains unclear. This study aimed to determine if pat

Hepatic DPP4 DNA methylation associates with fatty liver

Hepatic DPP4 expression is elevated in subjects with ectopic fat accumulation in the liver. However, whether increased dipeptidyl peptidase 4 (DPP4) is involved in the pathogenesis or is rather a consequence ofmetabolic disease is not known. We therefore studied the transcriptional regulation of hepatic Dpp4 in young mice prone to diet-induced obesity. Already at 6 weeks of age, expression of hepa

A Syntenic Cross Species Aneuploidy Genetic Screen Links RCAN1 Expression to β-Cell Mitochondrial Dysfunction in Type 2 Diabetes

Type 2 diabetes (T2D) is a complex metabolic disease associated with obesity, insulin resistance and hypoinsulinemia due to pancreatic β-cell dysfunction. Reduced mitochondrial function is thought to be central to β-cell dysfunction. Mitochondrial dysfunction and reduced insulin secretion are also observed in β-cells of humans with the most common human genetic disorder, Down syndrome (DS, Trisomy

Structures of apolipoprotein A-I in high density lipoprotein generated by electron microscopy and biased simulations

Background: Apolipoprotein A-I (apoA-I) in high-density lipoprotein (HDL) is a key protein for the transport of cholesterol from the vascular wall to the liver. The formation and structure of nascent HDL, composed of apoA-I and phospholipids, is critical to this process. Methods: The HDL was assembled in vitro from apoA-I, cholesterol and 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) at

Structural and Functional Analyses of Xyloside-primed Glycosaminoglycans

Glycosaminoglycans (GAGs) are polysaccharides produced by essentially all mammalian cells. Due to their enormous structural diversity, they are involved in many biological processes both in health and disease, including all stages of tumor progression. GAGs are normally attached to a core protein as a part of a proteoglycan; however, GAG biosynthesis can be induced by compounds composed of a xylos

HLA, infections and inflammation in early stages of atherosclerosis in children with type 1 diabetes

Aims This prospective study focuses on risk factors for arterial damage in children with type 1 diabetes (T1D). Methods Eighty children and adolescents with T1D were investigated twice, approximately 2 years apart, for carotid artery intima-media thickness (cIMT) and compliance (CAC), flow-mediated dilatation (FMD) of the brachial artery, and plasma levels of matrix metalloproteinase (MMP)-8. Al

Glucose-induced Changes in Gene Expression in Human Pancreatic Islets - Causes or Consequences of Chronic Hyperglycemia

Dysregulation of gene expression in islets from type 2 diabetic patients might be causally involved in the development of hyperglycemia or it could develop as a consequence of hyperglycemia, i.e. glucotoxicity. To separate the genes potentially causally involved in pathogenesis from those likely to be secondary to the hyperglycemia we exposed islets from human donors to normal or high glucose conc

Sulforaphane improves disrupted ER-mitochondria interactions and suppresses exaggerated hepatic glucose production

Aims: Exaggerated hepatic glucose production is one of the hallmarks of type 2 diabetes. Sulforaphane (SFN) has been suggested as a new potential anti-diabetic compound. However, the effects of SFN in hepatocytes are yet unclear. Accumulating evidence points to the close structural contacts between the ER and mitochondria, known as mitochondria-associated ER membranes (MAMs), as important hubs for

Daily intake of milk powder and risk of celiac disease in early childhood : A nested case-control study

Milk powder and gluten are common components in Swedish infants’ diets. Whereas large intakes of gluten early in life increases the risk of celiac disease in genetically at-risk Swedish children, no study has yet evaluated if intake of milk powder by 2 years of age is associated with celiac disease. A 1-to-3 nested case-control study, comprised of 207 celiac disease children and 621 controls match

Spectroscopic differences in posterior insula in patients with chronic temporomandibular pain

Chronic pain including temporomandibular disorder (TMD) pain involves a complex interplay between peripheral and central sensitization, endogenous modulatory pathways, cortical processing and integration and numerous psychological, behavioral and social factors. The aim of this study was to compare spectroscopic patterns of N-Acetyl-aspartate (NAA), total creatine (tCr), choline (Cho), myo-inosito

IL-16/miR-125a axis controls neutrophil recruitment in pristane-induced lung inflammation

Severe lung inflammation and alveolar hemorrhage can be life-threatening in systemic lupus erythematosus (SLE) patients if not treated early and aggressively. Neutrophil influx is the driver key of this pathology, but little is known regarding the molecular events regulating this recruitment. Here, we uncover a role for IL-16/mir-125a in this pathology and show not only that IL-16 is a target for

RORB and RORC associate with human islet dysfunction and inhibit insulin secretion in INS-1 cells

Little is known about the expression and function of Retinoic acid-related orphan receptors (RORA, B, and C) in pancreatic β cells. Here in, we utilized cDNA microarray and RNA sequencing approaches to investigate the expression pattern of ROR receptors in normal and diabetic human pancreatic islets. Possible correlations between RORs expression and HbA 1c levels as well as insulin secretory cap