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Evidence for Presence and Functional Effects of Kv1.1 Channels in beta-Cells: General Survey and Results from mceph/mceph Mice

Background: Voltage-dependent K+ channels (Kv) mediate repolarisation of beta-cell action potentials, and thereby abrogate insulin secretion. The role of the Kv1.1 K+ channel in this process is however unclear. We tested for presence of Kv1.1 in different species and tested for a functional role of Kv1.1 by assessing pancreatic islet function in BALB/cByJ (wild-type) and megencephaly (mceph/mceph)

Genetic variants for liver fat accumulation and circulating triglyceride levels

Non-alcoholic fatty liver disease (NAFLD), obesity and type 2 diabetes(T2D) are strongly associated and today their prevalence reaches epidemic proportions. NAFLD has a multi-factorial aetiology, both genetic and environmental factors are equally important. The aim of this thesis was to investigate genetic factors associating with NAFLD and circulating triglyceride (TG) levels in overweight or obe

Evaluation of the aldose reductase inhibitor fidarestat on ischemia-reperfusion injury in rat retina

This study evaluated the effects of retinal ischemia-reperfusion (IR) injury and pre-treatment with the potent and specific aldose reductase inhibitor fidarestat on apoptosis, aldose reductase and sorbitol dehydrogenase expression, sorbitol pathway intermediate concentrations, and oxidative-nitrosative stress. Female Wistar rats were pre-treated with either vehicle (N-methyl-D-elucamine) or fidare

Cost-effectiveness of insulin detemir compared with NPH insulin in people with type 2 diabetes in Denmark, Finland, Norway, and Sweden.

Abstract Objective: To assess the cost-effectiveness of insulin detemir compared with Neutral Protamine Hagedorn (NPH) insulin when initiating insulin treatment in people with type 2 diabetes mellitus (T2DM) in Denmark, Finland, Norway, and Sweden. Methods: Efficacy and safety data were derived from a 20-week multi-centre randomized controlled head-to-head clinical trial comparing insulin detemir

Decline in Titers of Anti-Idiotypic Antibodies Specific to Autoantibodies to GAD65 (GAD65Ab) Precedes Development of GAD65Ab and Type 1 Diabetes.

The humoral Idiotypic Network consisting of antibodies and their anti-idiotypic antibodies (anti-Id) can be temporarily upset by antigen exposure. In the healthy immune response the original equilibrium is eventually restored through counter-regulatory mechanisms. In certain autoimmune diseases however, autoantibody levels exceed those of their respective anti-Id, indicating a permanent disturbanc

Loss of Function of the Melanocortin 2 Receptor Accessory Protein 2 Is Associated with Mammalian Obesity

Melanocortin receptor accessory proteins (MRAPs) modulate signaling of melanocortin receptors in vitro. To investigate the physiological role of brain-expressed melanocortin 2 receptor accessory protein 2 (MRAP2), we characterized mice with whole-body and brain-specific targeted deletion of Mrap2, both of which develop severe obesity at a young age. Mrap2 interacts directly with melanocortin 4 rec

Metabolomic analyses reveal profound differences in glycolytic and tricarboxylic acid cycle metabolism in glucose-responsive and -unresponsive clonal beta-cell lines

Insulin secretion from pancreatic beta-cells is controlled by complex metabolic and energetic changes provoked by exposure to metabolic fuels. Perturbations in these processes lead to impaired insulin secretion, the ultimate cause of T2D (Type 2 diabetes). To increase our understanding of stimulus secretion coupling and metabolic processes potentially involved in the pathogenesis of T2D, a compreh

Immune therapy in type 1 diabetes mellitus.

Type 1 diabetes mellitus (T1DM) is an autoimmune disorder directed against the β cells of the pancreatic islets. The genetic risk of the disease is linked to HLA-DQ risk alleles and unknown environmental triggers. In most countries, only 10-15% of children or young adults newly diagnosed with T1DM have a first-degree relative with the disease. Autoantibodies against insulin, GAD65, IA-2 or the ZnT

Glutamate dehydrogenase, insulin secretion and Type 2 Diabetes. A new means to protect the pancreatic β-cell?

In this issue of Journal of Endocrinology, Dr Han and colleagues report a protective effect of the glutamate dehydrogenase-activator BCH under diabetes-like conditions that impair β-cell function in both a pancreatic β-cell line and in db/db mice. Based on these observations, the authors suggest that BCH could serve as novel treatment modality in Type 2 Diabetes. The present commentary discusses t

Decreased cord-blood phospholipids in young age at onset type 1 diabetes.

Children developing type 1 diabetes may have risk markers already in their umbilical cord blood. It is hypothesized that the risk for type 1 diabetes at an early age may be increased by a pathogenic pregnancy and be reflected in altered cord-blood composition. In this study metabolomics was used to test if the cord-blood lipidome was affected in children diagnosed with type 1 diabetes before eight

Fracture Mechanics of Collagen Fibrils: Influence of Natural Cross-Links

Tendons are important load-bearing structures, which are frequently injured in both sports and work. Type I collagen fibrils are the primary components of tendons and carry most of the mechanical loads experienced by the tissue, however, knowledge of how load is transmitted between and within fibrils is limited. The presence of covalent enzymatic cross-links between collagen molecules is an import

Children followed in the TEDDY study are diagnosed with type 1 diabetes at an early stage of disease.

The Environmental Determinants of Diabetes in the Young (TEDDY) study is designed to identify environmental exposures triggering islet autoimmunity and type 1 diabetes (T1D) in genetically high-risk children. We describe the first 100 participants diagnosed with T1D, hypothesizing that (i) they are diagnosed at an early stage of disease, (ii) a high proportion are diagnosed by an oral glucose tole

Stable Peptide of the Endogenous Opioid Enkephalin Precursor and Breast Cancer Risk.

In experimental studies, enkephalins (ENKs) and related opioids have been implicated as negative regulators of breast cancer development by enhancing immune-mediated tumoral defense as well as directly inhibiting cancer cells. We hypothesized that plasma levels of ENKs are predictive of the long-term breast cancer risk. Therefore, our objective was to measure pro-ENK A, a surrogate for mature ENK,

Rare variants in PPARG with decreased activity in adipocyte differentiation are associated with increased risk of type 2 diabetes

Peroxisome proliferator-activated receptor gamma (PPARG) is a master transcriptional regulator of adipocyte differentiation and a canonical target of antidiabetic thiazolidinedione medications. In rare families, loss-of-function (LOF) mutations in PPARG are known to cosegregate with lipodystrophy and insulin resistance; in the general population, the common P12A variant is associated with a decrea

Milk feeding and first complementary foods during the first year of life in the TEDDY study

The aim was to describe milk feeding patterns and first weaning foods during the first year of life in a large prospective birth cohort of infants with increased genetic risk for Type 1 diabetes (T1D) recruited in 4 different countries: the United States, Finland, Germany, and Sweden. All enrolled children with dietary information (n = 8,673) were included in the analyses; 1,307 (15%) children who

Impaired vibrotactile sense in children and adolescents with type 1 diabetes – Signs of peripheral neuropathy

Objective To investigate whether multi-frequency vibrometry can identify individuals with elevated vibration perception thresholds (VPTs), reflecting impaired vibrotactile sense, among children and adolescents with type 1 diabetes. Methods In 72 pediatric patients with type 1 diabetes, VPTs were evaluated for seven frequencies on two sites of the hand, and five frequencies on two sites of the foot