Oxidative stress, insulin signaling, and diabetes

Oxidative stress has been implicated as a contributor to both the onset and the progression of diabetes and its associated complications. Some of the consequences of an oxidative environment are the development of insulin resistance, β-cell dysfunction, impaired glucose tolerance, and mitochondrial dysfunction, which can lead ultimately to the diabetic disease state. Experimental and clinical data suggest an inverse association between insulin sensitivity and ROS levels. Oxidative stress can arise from a number of different sources, whether disease state or lifestyle, including episodes of ketosis, sleep restriction, and excessive nutrient intake. Oxidative stress activates a series of stress pathways involving a family of serine/threonine kinases, which in turn have a negative effect on insulin signaling. More experimental evidence is needed to pinpoint the mechanisms contributing to insulin resistance in both type 1 diabetics and nondiabetic individuals. Oxidative stress can be reduced by controlling hyperglycemia and calorie intake. Overall, this review outlines various mechanisms that lead to the development of oxidative stress. Intervention and therapy that alter or disrupt these mechanisms may serve to reduce the risk of insulin resistance and the development of diabetes.     

Effect of chromium niacinate and chromium picolinate supplementation on lipid peroxidation, TNF-alpha, IL-6, CRP, glycated hemoglobin, triglycerides, and cholesterol levels in blood of streptozotocin-treated diabetic rats

Chromium (Cr(3+)) supplementation facilitates normal protein, fat, and carbohydrate metabolism, and is widely used by the public in many countries. This study examined the effect of chromium niacinate (Cr-N) or chromium picolinate (Cr-P) supplementation on lipid peroxidation (LP), TNF-alpha, IL-6, C-reactive protein (CRP), glycosylated hemoglobin (HbA(1)), cholesterol, and triglycerides (TG) in diabetic rats. Diabetes (D) was induced in Sprague-Dawley rats by streptozotocin (STZ) (ip, 65 mg/kg BW). Control buffer, Cr-N, or Cr-P (400 microg Cr/kg BW) was administered by gavages daily for 7 weeks. Blood was collected by heart puncture using light anesthesia. Diabetes caused a significant increase in blood levels of TNF-alpha, IL-6, glucose, HbA(1), cholesterol, TG, and LP. Compared with D, Cr-N supplementation lowered the blood levels of TNF-alpha (P=0.04), IL-6 (P=0.02), CRP (P=0.02), LP (P=0.01), HbA(1) (P=0.02), TG (P=0.04), and cholesterol (P=0.04). Compared with D, Cr-P supplementation showed a decrease in TNF-alpha (P=0.02), IL-6 (P=0.02), and LP (P=0.01). Chromium niacinate lowers blood levels of proinflammatory cytokines (TNF-alpha, IL-6, CRP), oxidative stress, and lipids levels in diabetic rats, and appears to be a more effective form of Cr(3+) supplementation. This study suggests that Cr(3+) supplementation can lower the risk of vascular inflammation in diabetes.     

Sodium and potassium absorption by bean stem tissue

The effect of various periods of pretreatment in CaSO₄ solutions (aging) on the absorption of Na and K by bean stem slices was investigated. Freshly sliced tissue absorbed Na over the entire range of concentrations studied (0.02-50 mm). Potassium absorption by fresh tissue was nil at concentrations below 0.5 mm but at higher concentrations was similar to that of Na. When tissue was aged by aerating slices for 20 hr in 0.5 mm CaSO₄, K absorption was substantial over the entire range (0.01-50 mm), with evidence of a dual mechanism of absorption, whereas Na absorption was nil at concentrations below 0.2 mm. The formation of K-absorbing capacity with aging, and the loss of Na-absorbing capacity at low concentrations, were temperature-dependent and did not result from significant changes in rates of efflux of either ion. The absorption of Na by fresh tissue and K by aged tissue was sensitive to antimetabolites, with K uptake the more sensitive. Benzyladenine, an analog of kinetin, suppressed the formation of K-absorbing capability in aged tissue but did not prevent the loss of Naabsorbing capacity. Possible mechanisms for this alteration in ion-specificity of transport mechanisms are discussed.     

The regulation of mitochondrial DNA copy number in glioblastoma cells

As stem cells undergo differentiation, mitochondrial DNA (mtDNA) copy number is strictly regulated in order that specialized cells can generate appropriate levels of adenosine triphosphate (ATP) through oxidative phosphorylation (OXPHOS) to undertake their specific functions. It is not understood whether tumor-initiating cells regulate their mtDNA in a similar manner or whether mtDNA is essential for tumorigenesis. We show that human neural stem cells (hNSCs) increased their mtDNA content during differentiation in a process that was mediated by a synergistic relationship between the nuclear and mitochondrial genomes and results in increased respiratory capacity. Differentiating multipotent glioblastoma cells failed to match the expansion in mtDNA copy number, patterns of gene expression and increased respiratory capacity observed in hNSCs. Partial depletion of glioblastoma cell mtDNA rescued mtDNA replication events and enhanced cell differentiation. However, prolonged depletion resulted in impaired mtDNA replication, reduced proliferation and induced the expression of early developmental and pro-survival markers including POU class 5 homeobox 1 (OCT4) and sonic hedgehog (SHH). The transfer of glioblastoma cells depleted to varying degrees of their mtDNA content into immunocompromised mice resulted in tumors requiring significantly longer to form compared with non-depleted cells. The number of tumors formed and the time to tumor formation was relative to the degree of mtDNA depletion. The tumors derived from mtDNA depleted glioblastoma cells recovered their mtDNA copy number as part of the tumor formation process. These outcomes demonstrate the importance of mtDNA to the initiation and maintenance of tumorigenesis in glioblastoma multiforme.     

Nitrate Absorption by Barley: II. Influence of Nitrate Reductase Activity

The influence of protein synthesis and nitrate reductase activity on nitrate absorption by barley (Hordeum vulgare L.) was investigated. Cycloheximide decreased nitrate absorption. Pretreatment studies showed that cycloheximide affects either energy transfer or nitrate reductase activity or both.     

Pulmonary aspiration in preschool children with cystic fibrosis

Pulmonary aspiration of gastric refluxate (PAGR) has been demonstrated in association with pulmonary inflammation in school aged children with Cystic Fibrosis (CF). We sought to determine if similar findings were present in preschool children. Pepsin was measured in Broncho-alveolar lavage (BAL) fluid collected from clinically stable preschool children with CF and controls. Elevated pepsin levels were found in a subgroup of children with CF, but this was not found to be associated with pulmonary infection, pulmonary inflammation or respiratory or gastrointestinal symptoms.     

Simulated Effects of Stream Restoration on the Distribution of Wet‐Meadow Vegetation

Meadow restoration efforts typically involve the modification of stream channels to re‐establish hydrologic conditions necessary for the maintenance of native vegetation. To predict change in the distribution of common meadow plant species in response to meadow restoration, a hydrologic model was loosely coupled to a suite of individual plant species distribution models. The approach was tested on a well‐documented meadow/stream restoration project on Bear Creek, a tributary to the Fall River in northeastern California, U.S.A. We developed a surface‐water and groundwater hydrologic model for the meadow. Vegetation presence and absence data from 170 plots were combined with simulated water‐table depth time series to develop habitat‐suitability models for 11 herbaceous plant species. In each model, the habitat suitability is predicted as a function of growing‐season, water‐table depth, and range. The hydrologic model was used to simulate water‐table depth time series for the pre‐ and post‐restoration conditions. These results were used to predict the spatial distribution of habitat suitability for the 11 herbaceous plant species. Model results indicate that restoration changed water levels throughout the study area, extending well beyond the near‐stream region. Model results also indicate an increase in the spatial distribution of suitable habitat for mesic vegetation and a concomitant decrease in the spatial distribution of suitable habitat for xeric vegetation. The methods utilized in this study could be used to improve setting of objective and performance measures in restoration projects in similar environments, in addition to providing a quantitative, science‐based approach to guide riparian restoration and active revegetation efforts.