Intracellular Ca2+ regulating proteins in vascular smooth muscle cells are altered with type 1 diabetes due to the direct effects of hyperglycemia

<p>Abstract</p> <p>Background</p> <p>Diminished calcium (Ca²⁺) transients in response to physiological agonists have been reported in vascular smooth muscle cells (VSMCs) from diabetic animals. However, the mechanism responsible was unclear.</p> <p>Methodology/Principal Findings</p> <p>VSMCs from autoimmune type 1 Diabetes Resistant Bio-Breeding (DR-BB) rats and streptozotocin-induced rats were examined for levels and distribution of inositol trisphosphate receptors (IP₃R) and the SR Ca²⁺pumps (SERCA 2 and 3). Generally, a decrease in IP₃R levels and dramatic increase in ryanodine receptor (RyR) levels were noted in the aortic samples from diabetic animals. Redistribution of the specific IP₃R subtypes was dependent on the rat model. SERCA 2 was redistributed to a peri-nuclear pattern that was more prominent in the DR-BB diabetic rat aorta than the STZ diabetic rat. The free intracellular Ca²⁺in freshly dispersed VSMCs from control and diabetic animals was monitored using ratiometric Ca²⁺sensitive fluorophores viewed by confocal microscopy. In control VSMCs, basal fluorescence levels were significantly higher in the nucleus relative to the cytoplasm, while in diabetic VSMCs they were essentially the same. Vasopressin induced a predictable increase in free intracellular Ca²⁺in the VSMCs from control rats with a prolonged and significantly blunted response in the diabetic VSMCs. A slow rise in free intracellular Ca²⁺in response to thapsigargin, a specific blocker of SERCA was seen in the control VSMCs but was significantly delayed and prolonged in cells from diabetic rats. To determine whether the changes were due to the direct effects of hyperglycemica, experiments were repeated using cultured rat aortic smooth muscle cells (A7r5) grown in hyperglycemic and control conditions. In general, they demonstrated the same changes in protein levels and distribution as well as the blunted Ca²⁺responses to vasopressin and thapsigargin as noted in the cells from diabetic animals.</p> <p>Conclusions/Significance</p> <p>This work demonstrates that the previously-reported reduced Ca²⁺signaling in VSMCs from diabetic animals is related to decreases and/or redistribution in the IP₃R Ca²⁺channels and SERCA proteins. These changes can be duplicated in culture with high glucose levels.</p

Time-Dependent Alterations in Rat Macrovessels with Type 1 Diabetes

Vascular complications are associated with the progressive severity of diabetes, resulting in significant morbidity and mortality. This study quantifies functional vascular parameters and macrovascular structure in a rat model of type 1 diabetes. While there was no difference in the systemic arterial elastance (Ea) with 50 days of diabetes, changes were noted in the aorta and femoral artery including increased tunica media extracellular matrix content, decreased width of both the media and individual smooth muscle cell layers, and increased incidence of damaged mitochondria. Extracellular matrix proteins and elastin levels were significantly greater in the aorta of diabetic animals. These differences correlated with diminished matrix metalloprotease activity in the aorta of the diabetic animals. In conclusion, diabetes significantly altered the structure and ultrastructure of the aorta and femoral artery before systemic changes in arterial elastance could be detected

Evaluation of emmer wheat genetics resources aimed at dietary food production

Emmer wheat cultivated by organic farmers is used as a component of some bio (organic) food products. Its positive influence on consumer health is caused by grain composition. In the set of 8 emmer wheat accessions, the main grain components, bread making characteristics and contents of health supporting chemical substances such as total dietary fibre content and its components, content of total polyphenols plus catechin and ferulic acid contents, vitamins of the B group and E plus total content of carotenoids were evaluated by standard methods

Resistance exercise training lowers HbA1c more than aerobic training in adults with type 2 diabetes

<p>Abstract</p> <p>Background</p> <p>The aim of this study was to compare the effects of 10 weeks of resistance or treadmill exercises on glycemic indices levels prior to and immediately following exercise in adults with type 2 diabetes.</p> <p>Research Design and Method</p> <p>Twenty inactive subjects (mean age 53.5 years) with type 2 diabetes enrolled in the study. Baseline HbA1c, blood glucose levels, heart rate, and blood pressure were measured for each subject prior to the initiation of the exercise program. Subsequently, subjects were matched to age, waist circumference and sex and assigned to either isocaloric resistance or treadmill exercise groups, which met 3 times per week for 10 weeks.</p> <p>Results</p> <p>Both groups showed a reduction in pre and post-exercise blood glucose and HbA1c values. There was no change in resting blood pressure or heart rate in either group during the course of the 10 week intervention. The group receiving resistance exercises showed significant differences in the daily pre-exercise plasma glucose readings between the beginning and end of the exercise protocol (p < 0.001). There were significant improvements in the mean HbA1c reading pre and post training in both groups (p < 0.001). However, the greater reduction was noted in the resistance exercise group, and at 10 weeks their HbA1c levels were significantly lower than the group that received treadmill exercises (p < 0.006).</p> <p>Conclusion</p> <p>Ten weeks of resistance exercises were associated with a significantly better glycemic control in adults with type 2 diabetes compared to treadmill exercise.</p

In-situ spectroscopy of intrinsic Bi2Te3 topological insulator thin films and impact of extrinsic defects

Combined in-situ x-ray photoemission spectroscopy, scanning tunnelling spectroscopy and angle resolved photoemission spectroscopy of molecular beam epitaxy grown Bi2Te3 on lattice mismatched substrates reveal high quality stoichiometric thin films with topological surface states without a contribution from the bulk bands at the Fermi energy. The absence of bulk states at the Fermi energy is achieved without counter doping. We observe that the surface morphology and electronic band structure of Bi2Te3 are not affected by in-vacuo storage and exposure to oxygen, whereas major changes are observed when exposed to ambient conditions. These films help define a pathway towards intrinsic topological devices.Comment: 8 pages, 5 figure

Pancreatic islet transplantation to treat diabetes - defining molecular tools to select suitable islets [abstract]

Comparative Medicine - OneHealth and Comparative Medicine Poster SessionA complete understanding of pancreatic islet biology is essential to the development of preventive or curative interventions for diabetes. It has been known that subpopulations of islets of different sizes exist; however, whether they are biologically and functionally unique has not been investigated. As an example, our work comparing the biology of large versus small islets isolated from rats showed that small islets were superior to large islets in in vitro function and in transplantation outcomes. These results provided the stimulus for an improved approach to islet transplantation in humans. The work also led to new questions regarding the basic physiology of healthy islets. Through collaboration between our University of Kansas Medical Center and Children's Mercy Hospital teams, we determined that small islets secrete higher amount of insulin in vitro when compared to the large islets. We sought to identify whether the islet subpopulations showed differences at the molecular level and thus we investigated their protein expression profiles using two-dimensional polyacrylamide gel electrophoresis (2D PAGE). We found that the protein repertoire in the small and large islets differed significantly. Specifically, some proteins were found only in one type of islets, small or large, while they were missing or their expression levels were different in the other subpopulation. We identified some of the proteins by liquid chromatography - mass spectrometry. Immunofluorescence performed on small and large islets in pancreatic sections, with antibodies against identified proteins, confirmed that the proteins were present in one subpopulation of islets. Of these proteins, at least one was unique to large islets and can potentially be used as a marker to distinguish in vivo between islets that are high-insulin producers and those that fail to secrete significant amounts in insulin. Our long-term goal is to monitor the fate of the different islet populations during diabetes development. In addition, markers like this can be used to determine the best islet subpopulation for transplantation. The data support our hypothesis that integral differences exist between small and large islets that might determine the islets' unique properties under normal conditions and during the development of diabetes. These differences may also influence islet subpopulation behavior in transplantation affecting the outcome