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Effect of a common variant of the PCSK2 gene on reduced insulin secretion.

AIM/HYPOTHESIS: Individuals at risk of developing type 2 diabetes show a progressive decline in insulin secretion and increased insulin resistance over time. However, inability of the beta cells to compensate for the increased insulin resistance represents a key defect leading to overt type 2 diabetes. The aims of the present study were to replicate the association between genetic variants of the

ADP mediates inhibition of insulin secretion by activation of P2Y13 receptors in mice.

AIMS/HYPOTHESES: To investigate the effects of extracellular purines on insulin secretion from mouse pancreatic islets. METHODS: Mouse islets and beta cells were isolated and examined with mRNA real-time quantification, cAMP quantification and insulin and glucagon secretion. ATP release was measured in MIN6c4 cells. Insulin and glucagon secretion were measured in vivo after glucose injection. RESU

Laminin isoforms in atherosclerotic arteries from mice and man.

The properties of the arterial vasculature depend to a large extent on the activities of smooth muscle cells, which, in turn, are determined by their extracellular environment. During pathological conditions, such as atherosclerosis, this interaction is altered. In close proximity to medial smooth muscle cells are basement membrane components, such as different isoforms of laminin. These proteins

Common variant in the HMGA2 gene increases susceptibility to nephropathy in patients with type 2 diabetes.

AIMS/HYPOTHESIS: Type 2 diabetes is a chronic metabolic disorder associated with devastating microvascular complications. Genome-wide association studies have identified more than 60 genetic variants associated with type 2 diabetes and/or glucose and insulin traits, but their role in the progression of diabetes is not established. The aim of this study was to explore whether these variants were al

Validation of a multi-marker model for the prediction of incident type 2 diabetes mellitus: Combined results of the Inter99 and Botnia studies.

Purpose: To assess performance of a biomarker-based score that predicts the five-year risk of diabetes (Diabetes Risk Score, DRS) in an independent cohort that included 15-year follow-up. Method: DRS was developed on the Inter99 cohort, and validated on the Botnia cohort. Performance was benchmarked against other risk-assessment tools comparing calibration, time to event analysis, and net reclassi

Covariation of plasma ghrelin and motilin in irritable bowel syndrome.

We have previously shown that ghrelin is mainly localized to the stomach but also occurs, together with the prokinetic hormone motilin, in endocrine cells in the proximal small intestine. This study explored ghrelin and motilin concentrations in plasma in relation to gastrointestinal motility and whether plasma ghrelin is changed in patients with irritable bowel syndrome (IBS). Nine patients with

Strategic management of public affairs in Swedish multinational corporations - the recipe for success

This multiple case study addresses the question concerning how multinational corporations handle their public affairs operations. In general, public affairs regard public private sector collaboration and include how companies can manage their governmental stakeholders. Nevertheless, is there a recipe for managing this more successfully? Public affairs have long been an issue for companies operatin

How Two Modern Authors Have Rewritten Jane Austen’s Pride and Prejudice

When Jane Austen wrote Pride and Prejudice (1813), she created a formula that amateur and professional authors alike would follow. The heroine and the hero undergo a journey of emotional work as they figure out each other’s genuine intents. Two modern novels that are inspired by Pride and Prejudice are The Duke and I (2000) by Julia Quinn and Bridget Jones’s Diary (1996). This essay studies what t

Epigenetics and obesity: the devil is in the details

Obesity is a complex disease with multiple well-defined risk factors. Nevertheless, susceptibility to obesity and its sequelae within obesogenic environments varies greatly from one person to the next, suggesting a role for gene x environment interactions in the etiology of the disorder. Epigenetic regulation of the human genome provides a putative mechanism by which specific environmental exposur

Evaluation of A2BP1 as an Obesity Gene

OBJECTIVE-A genome-wide association study (GWAS) in Pima Indians (n = 413) identified variation in the ataxin-2 binding protein 1 gene (A2BP1) that was associated with percent body fat. On the basis of this association and the obese phenotype of ataxin-2 knockout mice, A2BP1 was genetically and functionally analyzed to assess its potential role in human obesity. RESEARCH DESIGN AND METHODS-Variant

A genome-wide approach accounting for body mass index identifies genetic variants influencing fasting glycemic traits and insulin resistance

Recent genome-wide association studies have described many loci implicated in type 2 diabetes (T2D) pathophysiology and beta-cell dysfunction but have contributed little to the understanding of the genetic basis of insulin resistance. We hypothesized that genes implicated in insulin resistance pathways might be uncovered by accounting for differences in body mass index (BMI) and potential interact

Long-term changes in dietary and food intake behaviour in the Diabetes Prevention Program Outcomes Study

Aims To compare change in dietary intake, with an emphasis on food groups and food intake behaviour, over time across treatment arms in a diabetes prevention trial and to assess the differences in dietary intake among demographic groups within treatment arms. Methods Data are from the Diabetes Prevention Program and Diabetes Prevention Program Outcomes Study. Participants were randomized to a life

Genetic predisposition to long-term non-diabetic deteriorations in glucose homeostasis: ten-year follow-up of the GLACIER Study.

To assess whether recently discovered genetic loci associated with hyperglycemia also predict long-term changes in glycemic traits. Methods: Sixteen fasting glucose-raising loci were genotyped in middle-aged adults from the GLACIER Study, a population-based prospective cohort study from Northern Sweden. Genotypes were tested for association with baseline fasting and 2-hr post-challenge glycemia (N

Water footprint assessment for water stewardship in the agri-food sector

The water footprint assessment framework aims to illustrate the full impact of water consumption in the whole life cycle of a product, from direct water extraction to water pollution. The framework provides a comprehensive indicator for water resources which, if used with care, can provide detailed information about the different impacts of water consumption in order to aid with water stewardship

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Single Fusion Pore Analysis via Single Cell Amperometry Uncovers Impaired Pore Expansion That Restricts Insulin Exocytosis in Human Type 2 Diabetes

Insulin secretion from vesicles within pancreatic beta cells occurs through the rapid (≤10 ms) process of exocytosis. A crucial final step in this process is the formation of a fusion pore, which connects the insulin vesicle interior to the extracellular space and insulin secretion rate. We employed real-time single-cell amperometry (SCA) with microsensors to quantitatively and dynamically monitor

Whole genome transcriptional analysis of intestinal biopsies and blood cells indicate genes involved in antioxidant defense systems, amino acid metabolism and antigen presentation in the pathogenesis of celiac disease

Background: Celiac disease is associated with HLA-risk haplotypes, but non-HLA genes and environmental factors are also linked to disease susceptibility. In this study, we explore the molecular pathways involved in celiac disease by analyzing the differential expression of genes in both the gut and peripheral blood across various celiac disease phenotypes. Methods: Whole genome RNA sequencing was