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Does immune-tolerance treatment with Alum-formulated GAD65 protect insulin-production in the pancreatic islet β cells?

Type 1 diabetes is a serious chronic disease in which the pancreatic islet beta cells are destroyed by autoimmunity specifically directed to intracellular autoantigens. Still undefined environmental factors are likely to initiate the disease process. One of the autoantigens is glutamic acid decarboxylase (GAD65) and attempts are made to induce immunological tolerance against this autoantigen. Alum

Continuous full filling capillary electrochromatography-electrospraying chromatographic nanoparticles

The influence of instrumental parameters affecting the ionization in continuous full filling capillary electrochromatography/electrospray ionization mass spectrometry (CFF-CEC/ESI-MS) was investigated. The investigated parameters were the BGE and sheath liquid ion strength and organic modifier content, the nebulizer gas pressure, and the concentration of nanoparticles in the BGE. It was found that

Optogenetic Control of Pancreatic Islets.

In light of the emerging diabetes epidemic, new experimental approaches in islet research are needed to elucidate the mechanisms behind pancreatic islet dysfunction and to facilitate the development of more effective therapies. Optogenetics has created numerous new experimental tools enabling us to gain insights into processes little was known about before. The spatial and temporal precision that

Calcium Modulation of Exocytosis-Linked Plasma Membrane Potential Oscillations in INS-1 832/13 Cells.

In the presence of high glucose or pyruvate, INS-1 832/13 insulinoma cells undergo stochastic oscillations in plasma membrane potential (Δψp) leading to associated fluctuations in cytosolic free Ca(2+) concentration ([Ca(2+)]c). Oscillations are not driven by upstream metabolic fluctuations, but rather by autonomous ionic mechanisms, the details of which are unclear. We have investigated the natur

Streptococcal M1 protein triggers chemokine formation, neutrophil infiltration, and lung injury in an NFAT-dependent manner.

Streptococcus pyogenes of the M1 serotype can cause STSS, which is associated with significant morbidity and mortality. The purpose of the present study was to examine the role of NFAT signaling in M1 protein-induced lung injury. NFAT-luc mice were treated with the NFAT inhibitor A-285222 before administration of the M1 protein. Neutrophil infiltration, edema, and CXC chemokines were quantified in

Glucagon-Like Peptide 1 Stimulates Insulin Secretion via Inhibiting RhoA/ROCK Signaling and Disassembling Glucotoxicity-Induced Stress Fibers

Chronic hyperglycemia leads to pancreatic beta-cell dysfunction characterized by diminished glucose-stimulated insulin secretion (GSIS), but the precise cellular processes involved are largely unknown. Here we show that pancreatic beta-cells chronically exposed to a high glucose level displayed substantially increased amounts of stress fibers compared with beta-cells cultured at a low glucose leve

An atlas of G-protein coupled receptor expression and function in human subcutaneous adipose tissue.

G-protein coupled receptors (GPCRs) are involved in the regulation of adipose tissue function, but the total number of GPCRs expressed by human subcutaneous adipose tissue, as well as their function and interactions with drugs, is poorly understood. We have constructed an atlas of all GPCRs expressed by human subcutaneous adipose tissue: the 'adipose tissue GPCRome', to support the exploration of

Neuropeptide Y is a minor autoantigen in newly diagnosed type 1 diabetes patients.

Autoantibodies (A) against Neuropeptide Y (NPY), was reported in 9% newly diagnosed type 1 diabetes (T1D) patients. A single nucleotide polymorphism (SNP) at rs16139 (T1128C) within the NPY-gene identified an amino acid substitution from leucine (L) to proline (P) (L7P) associated with both glucose tolerance and type 2 diabetes. We aimed to determine: (i) the influence of autoantibodies to leucine

Recruited brain tumor-derived mesenchymal stem cells contribute to brain tumor progression.

The identity of the cells that contribute to brain tumor structure and progression remains unclear. Mesenchymal stem cells (MSCs) have recently been isolated from normal mouse brain. Here, we report the infiltration of MSC-like cells into the GL261 murine glioma model. These Brain Tumor derived Mesenchymal Stem Cells (BT-MSCs) are defined with the phenotype (Lin-Sca-1+CD9+CD44+CD166+/-) and have m

Antibodies to influenza virus A/H1N1 hemagglutinin in type 1 diabetes children diagnosed before, during and after the Swedish A(H1N1)pdm09 vaccination campaign 2009-2010.

We determined A/H1N1-HA antibodies in relation to HLA-DQ genotypes and islet autoantibodies at clinical diagnosis in 1141 incident 0.7-18 years old type 1 diabetes patients diagnosed April 2009 - December 2010. Antibodies to (35) S-methionine-labeled A/H1N1 hemagglutinin were determined in a radiobinding assay in patients diagnosed before (n=325), during (n=355) and after (n=461) the October 2009

ADP receptor P2Y(13) induce apoptosis in pancreatic beta-cells.

Pancreatic beta-cell loss represents a key factor in the pathogenesis of diabetes. Since the influence of purinergic signaling in beta-cell apoptosis has not been much investigated, we examined the role of the ADP receptor P2Y(13) using the pancreatic insulinoma-cell line MIN6c4 as a model system. Real time-PCR revealed high expression of the ADP receptors P2Y(1) and P2Y(13). Adding the ADP analog

Excess mortality in middle-aged men with diabetes aged 15-34 years at diagnosis.

The aim of this study is to assess mortality risk and the excess of risk in patients with diabetes. Patients were 15-34 years old at diagnosis of diabetes mellitus (n = 879) in 1992 and 1993 in this national cohort from Sweden. Healthy controls were matched for gender and birth on the same day as the index cases (n = 837). The civic registration number was used to link patients and controls to the

Cocaine- and amphetamine-regulated transcript is expressed in adipocytes and regulate lipid- and glucose homeostasis.

Cocaine- and amphetamine-regulated transcript (CART) is a regulatory peptide expressed in the nervous system and in endocrine cells, e.g. in pancreatic islets. CART deficient mice exhibit islet dysfunction, impaired insulin secretion and increased body weight. A mutation in the CART gene in humans is associated with reduced metabolic rate, obesity and diabetes. Furthermore, CART is upregulated in

First Report on Metastasizing Small Bowel Carcinoids in First-Degree Relatives in Three Generations

Background/Aims: There is an established association between the multiple endocrine neoplasia type 1 (MEN 1) syndrome and foregut carcinoids. Some registry studies also indicate that offspring to carcinoid patients run an increased risk of developing a carcinoid tumor themselves. However, there are only scattered reports of gastrointestinal carcinoids in two generations. The aim of this study was

Development of a gas chromatography/mass spectrometry based metabolomics protocol by means of statistical experimental design

Metabolomics is a growing research field where new protocols are rapidly developed and new applications discovered. Common applications include biomarker discovery and elucidation of drug metabolism. However, the development of such protocols rarely includes a systematic optimization followed by validation with real samples. Here a GC/MS-based protocol using methoximation followed by silylation wi

Matrix Metalloproteinases - keys to healthier blood vessels in diabetes?

In this issue of J Endocrinol, Schuyler et al. show that intimal lesions in atherosclerosis-prone diabetic apoE-/- mice are reduced by insulin treatment. An increase of metalloproteinase-9 expression was observed in untreated diabetic apoE-/- mice; this was absent in insulin-treated mice. The study suggests that hindering of tissue-remodeling metalloproteinases may account for the beneficial effec

Long-term sustained autoimmune response to beta cell specific zinc transporter (ZnT8, W, R, Q) in young adult patients with preserved beta cell function at diagnosis of diabetes.

The aim of this study was to examine whether autoantibodies to: ZnT8-Tryptophan (ZnT8WA), ZnT8-Arginine (ZnT8RA) or ZnT8-Glutamine (ZnT8QA) correlated with C-peptide or other autoantibodies and to assess diagnostic sensitivity of ZnT8WRQA. Specimens from 270 newly diagnosed diabetic subjects (age 15--34 years) and after five 5 years duration of disease were examined. Four linear regression models