Interleukin-1 inhibits glucose-induced Ca2+ uptake by islets of Langerhans

AbstractRecombinant interleukin-1 (rIL-1) is known to inhibit glucose-induced insulin secretion by islets of Langerhans, a novel target tissue of cytokine. We have investigated whether rIL-1 pretreatment affects biochemical mechanisms known to be involved in the regulation of Ca2+ homeostasis during glucose-induced insulin secretion. Glucose-induced Ca2+ uptake by intact islets through the plasma membrane was dramatically inhibited (96%) by rIL-1 (2 nM). rIL-1, however, did not affect Ca2+ uptake by, or Ins 1,4,5-P3-induced Ca2+ efflux from, the endoplasmic reticulum in digitonin-permeabilized islets, although glucose-induced accumulation of inositol trisphosphates was inhibited (38%). These results suggest that perturbation of intracellular Ca2+ homeostasis in islets is involved in inhibition of insulin secretion by rIL-1

Interleukin-1 induces rapid and transient expression of the c-fos proto-oncogene in isolated pancreatic islets and in purified β-cells

AbstractThe effect of interleukin-1β (IL-1) on expression of c-fos mRNA in isolated rat pancreatic islets was examined. Accumulation of c-fos mRNA was demonstrable after 30 min of exposure to IL-1, peaked by 60 min, and declined thereafter. Fluorescence-activated cell sorting (FACS) of dispersed islet cells was employed to localize the accumulation of c-fos mRNA to the β-cell. Cycloheximide did not influence the induction of c-fos mRNA by IL-1. Accumulation of c-fos mRNA therefore appears to be an early signal transduction event in the β-cell and a component of the cellular mechanism(s) by which IL-1 influences β-cell function

Estimating the Effects of Weather, Dry Matter Intake, and Body Weight on Daily Water Intake in Weaned Calves

Objective The purpose of this study was to study the effect of weather, dry matter intake, and body weight on the water requirements of weaned calves and estimating the requirements in a model.Study Description Weaned steers (n=48) were selected to study the effects of the weather, body weight, and dry matter intake on water intake in the winter (n=24) and summer (n=24) months. Calves were provided with ad libitum access to feed and water at the SDSU Cow-Calf Education and Research Facility (CCERF) and measured utilizing an automated feed and water system (Insentec, The Hague, Netherlands). Temperature, humidity, precipitation, wind speed, solar radiation, and air pressure were recorded at a Mesonet automated weather station in Brookings, SD (located 2.4 miles from the SDSU CCERF). Effects of climate data, body weight, and daily dry matter intake on daily water intake will be analyzed utilizing a mixed-effects model

A novel strategy to increase the proliferative potential of adult human β-cells while maintaining their differentiated phenotype

Our previous studies demonstrated that Wnt/GSK-3/β-catenin and mTOR signaling are necessary to stimulate proliferative processes in adult human β-cells. Direct inhibition of GSK-3, that engages Wnt signaling downstream of the Wnt receptor, increases β-catenin nuclear translocation and β-cell proliferation but results in lower insulin content. Our current goal was to engage canonical and non-canonical Wnt signaling at the receptor level to significantly increase human β-cell proliferation while maintaining a β-cell phenotype in intact islets. We adopted a system that utilized conditioned medium from L cells that expressed Wnt3a, R-spondin-3 and Noggin (L-WRN conditioned medium). In addition we used a ROCK inhibitor (Y-27632) and SB-431542 (that results in RhoA inhibition) in these cultures. Treatment of intact human islets with L-WRN conditioned medium plus inhibitors significantly increased DNA synthesis ∼6 fold in a rapamycin-sensitive manner. Moreover, this treatment strikingly increased human β-cell proliferation ∼20 fold above glucose alone. Only the combination of L-WRN conditioned medium with RhoA/ROCK inhibitors resulted in substantial proliferation. Transcriptome-wide gene expression profiling demonstrated that L-WRN medium provoked robust changes in several signaling families, including enhanced β-catenin-mediated and β-cell-specific gene expression. This treatment also increased expression of Nr4a2 and Irs2 and resulted in phosphorylation of Akt. Importantly, glucose-stimulated insulin secretion and content were not downregulated by L-WRN medium treatment. Our data demonstrate that engaging Wnt signaling at the receptor level by this method leads to necessary crosstalk between multiple signaling pathways including activation of Akt, mTOR, Wnt/β-catenin, PKA/CREB, and inhibition of RhoA/ROCK that substantially increase human β-cell proliferation while maintaining the β-cell phenotype

Performance analysis of co-firing waste materials in an advanced pressurized fluidized-bed combustor

The co-firing of waste materials with coal in utility scale power plants has emerged as an effective approach to produce energy and manage municipal wastes. Leading this approach is the atmospheric fluidized-bed combustor (AFBC). It has demonstrated its commercial acceptance in the utility market as a reliable source of power by burning a variety of waste and alternative fuels. The application of pressurized fluidized-bed combustor (PFBC) technology, although relatively new, can provide significant enhancements to the efficient production of electricity while maintaining the waste management benefits of AFBC. A study was undertaken to investigate the technical and economical feasibility of co-firing a PFBC with coal and municipal and industrial wastes. Focus was placed on the production of electricity and the efficient disposal of wastes for application in central power station and distributed locations. Issues concerning waste material preparation and feed, PFBC operation, plant emissions, and regulations are addressed. The results and conclusions developed are generally applicable to current and advanced PFBC design concepts. Wastes considered for co-firing include municipal solid waste (MSW), sewage sludge, and industrial de-inking sludge. Conceptual designs of two power plants rated at 250 MWe and 150 MWe were developed. Heat and material balances were completed for each plant along with environmental issues. With the PFBC`s operation at high temperature and pressure, efforts were centered on defining feeding systems capable of operating at these conditions. Air emissions and solid wastes were characterized to assess the environmental performance comparing them to state and Federal regulations. This paper describes the results of this investigation, presents conclusions on the key issues, and provides recommendations for further evaluation

Measuring individual overpotentials in an operating solid-oxide electrochemical cell

We use photo-electrons as a non-contact probe to measure local electrical potentials in a solid-oxide electrochemical cell. We characterize the cell in operando at near-ambient pressure using spatially-resolved X-ray photoemission spectroscopy. The overpotentials at the interfaces between the Ni and Pt electrodes and the yttria-stabilized zirconia (YSZ) electrolyte are directly measured. The method is validated using electrochemical impedance spectroscopy. Using the overpotentials, which characterize the cell's inefficiencies, we compare without ambiguity the electro-catalytic efficiencies of Ni and Pt, finding that on Ni H_2O splitting proceeds more rapidly than H2 oxidation, while on Pt, H2 oxidation proceeds more rapidly than H2O splitting.Comment: corrected; Phys. Chem. Chem. Phys., 201

β-cell metabolic alterations under chronic nutrient overload in rat and human islets

The aim of this study was to assess multifactorial β-cell responses to metabolic perturbations in primary rat and human islets. Treatment of dispersed rat islet cells with elevated glucose and free fatty acids (FFAs, oleate:palmitate = 1:1 v/v) resulted in increases in the size and the number of lipid droplets in β-cells in a time- and concentration-dependent manner. Glucose and FFAs synergistically stimulated the nutrient sensor mammalian target of rapamycin complex 1 (mTORC1). A potent mTORC1 inhibitor, rapamycin (25 nM), significantly reduced triglyceride accumulation in rat islets. Importantly, lipid droplets accumulated only in β-cells but not in α-cells in an mTORC1-dependent manner. Nutrient activation of mTORC1 upregulated the expression of adipose differentiation related protein (ADRP), known to stabilize lipid droplets. Rat islet size and new DNA synthesis also increased under nutrient overload. Insulin secretion into the culture medium increased steadily over a 4-day period without any significant difference between glucose (10 mM) alone and the combination of glucose (10 mM) and FFAs (240 μM). Insulin content and insulin biosynthesis, however, were significantly reduced under the combination of nutrients compared with glucose alone. Elevated nutrients also stimulated lipid droplet formation in human islets in an mTORC1-dependent manner. Unlike rat islets, however, human islets did not increase in size under nutrient overload despite a normal response to nutrients in releasing insulin. The different responses of islet cell growth under nutrient overload appear to impact insulin biosynthesis and storage differently in rat and human islets