Search

The aim of this study was to estimate the prevalence of patients diagnosed with chronic obstructive pulmonary disease (COPD) according to age, gender, and residence in Greenland and to investigate the associated quality of care. The study was performed as an observational cross-sectional study using data on patients diagnosed with COPD, extracted from the electronical medical record (EMR) in Greenland. The total prevalence of patients aged 20–79 years diagnosed with COPD in Greenland in 2022 was 2.2%. The prevalence was significantly higher in the capital Nuuk compared to the remaining parts of Greenland (2.4% vs. 2.0%, respectively). Significantly more women than men were diagnosed with COPD, but the lung function of men was found to be significantly reduced/impaired compared to women. The prevalence of patients aged 40 years or above was 3.8%. The quality of care was significantly higher among patients living in Nuuk compared to the remaining parts of Greenland for eight out of ten quality indicators. The prevalence of COPD in Greenland is lower than in other comparable populations and might be underestimated. Continued focus on early detection of new cases and initiatives to improve and expand monitoring of quality-of-care measurements, including both additional clinical and patient reported outcomes, are recommended.

Context Metabolic disorders such as obesity represent a major health challenge. Obesity alone has reached epidemic proportions, with at least 2.8 million people worldwide dying annually from diseases caused by overweight or obesity. The brain–metabolic axis is central to maintain homeostasis under metabolic stress via an intricate signaling network of hormones. Protein interacting with C kinase 1 (PICK1) is important for the biogenesis of various secretory vesicles, and we have previously shown that PICK1-deficient mice have impaired secretion of insulin and growth hormone. Objective The aim was to investigate how global PICK1-deficient mice respond to high-fat diet (HFD) and assess its role in insulin secretion in diet-induced obesity. Methods We characterized the metabolic phenotype through assessment of body weight, composition, glucose tolerance, islet morphology insulin secretion in vivo, and glucose-stimulated insulin secretion ex vivo. Results PICK1-deficient mice displayed similar weight gain and body composition as wild-type (WT) mice following HFD. While HFD impaired glucose tolerance of WT mice, PICK1-deficient mice were resistant to further deterioration of their glucose tolerance compared with already glucose-impaired chow-fed PICK1-deficient mice. Surprisingly, mice with β-cell–specific knockdown of PICK1 showed impaired glucose tolerance both on chow and HFD similar to WT mice. Conclusion Our findings support the importance of PICK1 in overall hormone regulation. However, importantly, this effect is independent of the PICK1 expression in the β-cell, whereby global PICK1-deficient mice resist further deterioration of their glucose tolerance following diet-induced obesity.

Aims. Posttranslational modifications of histones and transcription factors regulate gene expression and are implicated in beta-cell failure and diabetes. We have recently shown that preserving H3K27 and H3K4 methylation using the lysine demethylase inhibitor GSK-J4 reduces cytokine-induced destruction of beta-cells and improves beta-cell function. Here, we investigate the therapeutic potential of GSK-J4 to prevent diabetes development and examine the importance of H3K4 methylation for islet function.Materials and Methods. We used two mouse models of diabetes to investigate the therapeutic potential of GSK-J4. To clarify the importance of H3K4 methylation, we characterized a mouse strain with knockout (KO) of the H3K4 demethylase KDM5B.Results. GSK-J4 administration failed to prevent the development of experimental diabetes induced by multiple low-dose streptozotocin or adoptive transfer of splenocytes from acutely diabetic NOD to NODscid mice. KDM5B-KO mice were growth retarded with altered body composition, had low IGF-1 levels, and exhibited reduced insulin secretion. Interestingly, despite secreting less insulin, KDM5B-KO mice were able to maintain normoglycemia following oral glucose tolerance test, likely via improved insulin sensitivity, as suggested by insulin tolerance testing and phosphorylation of proteins belonging to the insulin signaling pathway. When challenged with high-fat diet, KDM5B-deficient mice displayed similar weight gain and insulin sensitivity as wild-type mice.Conclusion. Our results show a novel role of KDM5B in metabolism, as KDM5B-KO mice display growth retardation and improved insulin sensitivity.

This study estimates the age- and sex-specific prevalence of patients receiving urate-lowering therapy (ULT) in Greenland and compares the results with estimates in Denmark. Characteristics of patients receiving ULT in Greenland were compared to age- and sex-matched controls. The study was designed as a cross-sectional case–control study based on nationwide data from medical and population registers in Greenland and Denmark. The prevalence of patients receiving ULT was significantly lower in Greenland (0.55%) compared to Denmark (1.40%) (p < 0.001). In both countries, the prevalence increased with age and was higher among men compared to women. In Greenland, patients receiving ULT were more often overweight, and more frequently received blood glucose-, lipid-, and blood pressure-lowering medicine including diuretics compared to age- and sex-matched controls. The prevalence of patients receiving ULT was significantly lower in Greenland compared to Denmark. Common life-style related risk factors for hyperuricemia and gout were observed frequently among ULT-treated patients compared to controls. Along with an increasing prevalence of lifestyle-related diseases in Greenland, the prevalence of patients receiving ULT may increase in the years to come. More focus on detection and management of hyperuricemia and gout in Greenland is warranted to improve quality of health care.

Depression is a mental illness affecting more than 260 million people worldwide. In Greenland, the prevalence of patients treated with antidepressant medicine (antidepressants) has not previously been investigated. The aim of this study was to estimate and compare the age- and gender-specific prevalence of patients treated with antidepressants in Greenland and Denmark. The study was a cross-sectional register study using data from population and medical registers in Greenland and Denmark. Included was 1,573 Greenlandic patients and 419,151 Danish patients treated with antidepressants, respectively. The overall prevalence of patients aged 10-89 years treated with antidepressants was 3.5% in Greenland, and 8.1% in Denmark, being significantly lower in Greenland compared to Denmark (p < 0.001). The age- and gender-specific prevalence was significantly lower for patients from Greenland compared to from Denmark. In both Greenland and Denmark, the prevalence of women receiving antidepressants was significantly higher than for men. Finally, there was regional differences in the prevalence of usage of antidepressants in Greenland. Undiagnosed depression might contribute to the lower prevalence in Greenland as well as limited access to primary healthcare.

Selective inhibition of histone deacetylase 3 (HDAC3) prevents glucolipotoxicity-induced &beta, cell dysfunction and apoptosis by alleviation of proapoptotic endoplasmic reticulum (ER) stress-signaling, but the precise molecular mechanisms of alleviation are unexplored. By unbiased microarray analysis of the &beta, cell gene expression profile of insulin-producing cells exposed to glucolipotoxicity in the presence or absence of a selective HDAC3 inhibitor, we identified Enhancer of zeste homolog 2 (EZH2) as the sole target candidate. &beta, Cells were protected against glucolipotoxicity-induced ER stress and apoptosis by EZH2 attenuation. Small molecule inhibitors of EZH2 histone methyltransferase activity rescued human islets from glucolipotoxicity-induced apoptosis. Moreover, EZH2 knockdown cells were protected against glucolipotoxicity-induced downregulation of the protective non-canonical Nuclear factor of kappa light polypeptide gene enhancer in B-cells (NF&kappa, B) pathway. We conclude that EZH2 deficiency protects from glucolipotoxicity-induced ER stress, apoptosis and downregulation of the non-canonical NF&kappa, B pathway, but not from insulin secretory dysfunction. The mechanism likely involves transcriptional regulation via EZH2 functioning as a methyltransferase and/or as a methylation-dependent transcription factor.

In management of fisheries, knowledge about the species is crucial due to differences in life history traits. The first step is therefore species identification. For many species this task is straightforward, however for some species e.g. the two species of Atlantic redfish Sebastes mentella and Sebastes norvegicus, it can be difficult for an untrained eye. With the goal to separate the two species, we analysed otolith shape variation of S. mentella and S. norvegicus caught on the continental slope of East Greenland using the R package “Shape R”. Results were evaluated against genetic analysis of the same fish, and compared to results of both a visual identification of the two species and a separation based on a linear discriminant analysis on standardised values of fish length, fish weight and otolith weight. It was concluded that the objective otolith shape analysis using the Shape R package analysis achieve a reasonable classification success, however with a clear bias towards S. mentella. Classification using the otolith weight achieved a slightly higher success than the shape analysis making it a promising method. Furthermore, the method is at the same time both objective, less time consuming than the otolith shape analysis and less expensive than genetic analysis. However, the visual classification method of the whole fish had the highest success rate of the three tested methods, which despite the need for trained technicians makes it the most successful method.

Background: Cyclooxygenase (COX) activity is increased in endoscopic normal colonic mucosa from patients with colorectal neoplasia (CRN). COX-2 is thought to be the predominant COX isozyme involved in neoplasia. Meanwhile, relative contributions of COX-1 and COX-2 isoforms are unknown. Knowledge about their mutual activity in colonic mucosa is important for diagnostics and targeted therapy for CRN. The aim of this study was to assess the relative function, expression and localization of COX-1 and COX-2 enzymes in colonic non-neoplastic human mucosa and thereby to potentially reveal a mucosal disease predisposition for better treatment. Methods: Biopsies were pinched from normal appearing colonic mucosa in patients undergoing endoscopy. Ussing chamber technique was applied for an indirect assessment of epithelial activity, RT-qPCR for expression and immunohistochemistry for localization of COX-1 and COX-2 enzymes in patients without (ctrls) and with a history of CRN (CRN-pts). Results: Combined COX-1 and COX-2 activity was higher in CRN-pts, p=0.036. COX-2 was primarily localized in absorptive cells, while COX-1 appeared to be restricted to nonenteroendocrine tuft cells of the colonic epithelium. Conclusions: In biopsies from endoscopic normal appearing colonic mucosa, combined activity of COX-1 and COX-2 enzymes is increased in CRN-pts compared with ctrls. This indicates that COX-1 and COX-2 together contribute to an increased proliferation process. Of note, in colonic epithelial cell lining, the COX-1 enzyme seems localized in tuft cells.

The ADAMTS9 rs4607103 C allele is one of the few gene variants proposed to increase the risk of type 2 diabetes through an impairment of insulin sensitivity. We show that the variant is associated with increased expression of the secreted ADAMTS9 and decreased insulin sensitivity and signaling in human skeletal muscle. In line with this, mice lacking Adamts9 selectively in skeletal muscle have improved insulin sensitivity. The molecular link between ADAMTS9 and insulin signaling was characterized further in a model where ADAMTS9 was overexpressed in skeletal muscle. This selective overexpression resulted in decreased insulin signaling presumably mediated through alterations of the integrin β1 signaling pathway and disruption of the intracellular cytoskeletal organization. Furthermore, this led to impaired mitochondrial function in mouse muscle—an observation found to be of translational character because humans carrying the ADAMTS9 risk allele have decreased expression of mitochondrial markers. Finally, we found that the link between ADAMTS9 overexpression and impaired insulin signaling could be due to accumulation of harmful lipid intermediates. Our findings contribute to the understanding of the molecular mechanisms underlying insulin resistance and type 2 diabetes and point to inhibition of ADAMTS9 as a potential novel mode of treating insulin resistance.

Transcriptional changes control β-cell survival in response to inflammatory stress. Posttranslational modifications of histone and non-histone transcriptional regulators activate or repress gene transcription, but the link to cell-fate signaling is unclear. Inhibition of lysine deacetylases (KDACs) protects β cells from cytokine-induced apoptosis and reduces type 1 diabetes incidence in animals. We hypothesized that also lysine demethylases (KDMs) regulate β-cell fate in response to inflammatory stress. Expression of the demethylase Kdm6B was upregulated by proinflammatory cytokines suggesting a possible role in inflammation-induced β-cell destruction. Inhibition of KDM6 demethylases using the selective inhibitor GSK-J4 protected insulin-producing cells and human and mouse islets from cytokine-induced apoptosis by blunting nuclear factor (NF)-κB signaling and endoplasmic reticulum (ER) stress response gene expression. GSK-J4 furthermore increased expression of insulin gene and glucose-stimulated insulin secretion. Expression of genes regulating purinergic and cytokine ligand-receptor interactions was downregulated following GSK-J4 exposure, while expression of genes involved in cell maintenance and survival was upregulated. These data suggest that KDMs are important regulators of inflammation-induced β-cell dysfunction and death.

Background Intracellular signaling through cyclic nucleotides, both cyclic AMP and cyclic GMP, is altered in colorectal cancer. Accordingly, it is hypothesized that an underlying mechanism for colorectal neoplasia involves altered function of phosphodiesterases (PDEs), which affects cyclic nucleotide degradation. Here we present an approach to evaluate the function of selected cyclic nucleotide-PDEs in colonic endoscopic biopsies from non-neoplastic appearing mucosa. Methods Biopsies were obtained from patients with and without colorectal neoplasia. Activities of PDEs were characterized functionally by measurements of transepithelial ion transport and their expression and localization by employing real-time qPCR and immunohistochemistry. Results In functional studies PDE subtype-4 displayed lower activity in colorectal neoplasia patients (p = 0.006). Furthermore, real-time qPCR analysis showed overexpression of subtype PDE4B (p = 0.002) and subtype PDE5A (p = 0.02) in colorectal neoplasia patients. Finally, immunohistochemistry for 7 PDE isozymes demonstrated the presence of all 7 isozymes, albeit with weak reactions, and with no differences in localization between colorectal neoplasia and control patients. Of note, quantification of PDE subtype immunostaining revealed a lower amount of PDE3A (p = 0.04) and a higher amount of PDE4B (p = 0.02) in samples from colorectal neoplasia patients. Conclusion In conclusion, functional data indicated lower activity of PDE4 subtypes while expressional and abundance data indicated a higher expression of PDE4B in patients with colorectal neoplasia. We suggest that cyclic nucleotide-PDE4B is overexpressed as a malfunctioning protein in non-neoplastic appearing colonic mucosa from patients with colorectal neoplasia. If a predisposition of reduced PDE4B activity in colonic mucosa from colorectal neoplasia patients is substantiated further, this subtype could be a potential novel early diagnostic risk marker and may even be a target for future medical preventive treatment of colorectal cancer. Electronic supplementary material The online version of this article (doi:10.1186/s12885-016-2980-z) contains supplementary material, which is available to authorized users.

Disease is conventionally viewed as the chaotic inappropriate outcome of deranged tissue function resulting from aberrancies in cellular processes. Yet the patho-biology of cellular dysfunction and death encompasses a coordinated network no less sophisticated and regulated than maintenance of homeostatic balance. Cellular demise is far from passive subordination to stress but requires controlled coordination of energy-requiring activities including gene transcription and protein translation that determine the graded transition between defensive mechanisms, cell cycle regulation, dedifferentiation and ultimately to the activation of death programmes. In fact, most stressors stimulate both homeostasis and regeneration on one hand and impairment and destruction on the other, depending on the ambient circumstances. Here we illustrate this bimodal ambiguity in cell response by reviewing recent progress in our understanding of how the pancreatic β cell copes with inflammatory stress by changing gene transcription and protein translation by the differential and interconnected action of reactive oxygen and nitric oxide species, microRNAs and posttranslational protein modifications.

Dietary advice is the cornerstone in first-line treatment of metabolic diseases. Nutritional interventions directed at these clinical conditions mainly aim to (a) improve insulin resistance by reducing energy-dense macronutrient intake to obtain weight loss and (b) reduce fluctuations in insulin secretion through avoidance of rapidly absorbable carbohydrates. However, even in the majority of motivated patients selected for clinical trials, massive efforts using this approach have failed to achieve lasting efficacy. Less attention has been given to the role of micronutrients in metabolic diseases. Here, we review the evidence that highlights (a) the importance of iron in pancreatic beta-cell function and dysfunction in diabetes and (b) the integrative pathophysiological effects of tissue iron levels in the interactions among the beta cell, gut microbiome, hypothalamus, innate and adaptive immune systems, and insulin-sensitive tissues. We propose that clinical trials are warranted to clarify the impact of dietary or pharmacological iron reduction on the development of metabolic disorders.

An insufficient functional β-cell mass is a prerequisite to develop diabetes. Thus, means to protect or restore β-cell mass are important goals in diabetes research. Inflammation and proinflammatory cytokines play important roles in β-cell dysfunction and death, and recent data show that 2 miRNAs, miR-21 and miR-34a, may be involved in mediating cytokine-induced β-cell dysfunction. Therefore, manipulation of miR-21 and miR-34a levels may potentially be beneficial to β cells. To study the effect of long-term alterations of miR-21 or miR-34a levels upon net β-cell number, we stably overexpressed miR-21 and knocked down miR-34a, and investigated essential cellular processes. miRNA expression was manipulated using Lentiviral transduction of the β-cell line INS-1. Stable cell lines were generated, and cell death, NO synthesis, proliferation, and total cell number were monitored in the absence or presence of cytokines.Overexpression of miR-21 decreased net β-cell number in the absence of cytokines, and increased apoptosis and NO synthesis in the absence and presence of cytokines. Proliferation was increased upon miR-21 overexpression. Knockdown of miR-34a increased net β-cell number in the absence of cytokines, and reduced apoptosis and NO synthesis in the absence and presence of cytokines. Proliferation was decreased upon miR-34a knockdown.As overexpression of miR-21 increased proliferation, but also apoptosis and NO synthesis, the potential of miR-21 as a therapeutic agent to increase β-cell survival is doubtful. Knockdown of miR-34a slightly decreased proliferation, but as apoptosis and NO synthesis were highly reduced, miR-34a may be further investigated as a therapeutic target to reduce β-cell death and dysfunction.