Endoplasmic reticulum stress increases glucose production in vivo via effects on liver glycogenolysis and glucose-6-phosphatase activity

Recent evidence suggests that endoplasmic reticulum (ER) stress can induce impairments in both insulin secretion and insulin action. The aim of the present study was to examine the effects of ER stress on glucose production in vivo. Fasted rats were anesthetized and catheters were placed in the carotid artery, jugular vein, and jejunal vein. A pancreatic clamp was performed in which somatostatin was infused to inhibit pancreatic insulin and glucagon secretion. These hormones were then replaced at basal levels. To examine the effects of ER stress on glucose production, 6,6-2H2 Glucose was infused in the absence (CON, n =4) or presence of jejunal vein tunicamycin delivery (TUN, n =6). TUN induces ER stress through inhibition of protein glycosylation. Arterial insulin, glucagon, corticosterone, and free fatty acid concentrations were constant throughout experiments and were not different between groups. Glucose concentration and production increased by 76.2+-24.2 mg/dl and 2.6+-1.2 mg/kg/min (mean+-SDEV), respectively, in TUN, but did not change in CON. Liver glucose-6-phosphatase (G6Pase) and phosphoenopyruvate carboxykinase mRNA were not different between groups. Liver, but not kidney, G6Pase activity (nmoles/mg protein/30min) was increased in TUN (7.2+-2.1) vs. CON (0.2+-0.3). Liver glycogen concentration was reduced by 62% in TUN vs. CON. These data suggest that experimental induction of ER stress can increase the production of glucose in vivo, in part, via activation of hepatic glycogenolysis and G6Pase.College Honors

Saturated Fatty Acid-Induced Cytotoxicity in Liver Cells Does Not Involve Phosphatase and Tensin Homologue Deleted on Chromosome 10

Liver specific deletion of the tumor suppressor phosphatase and tensin homologue deleted on chromosome 10 (PTEN) induces steatosis and hypersensitivity to insulin. Saturated fatty acids, which induce endoplasmic reticulum stress and cell death, appear to increase PTEN, whereas unsaturated fatty acids which do not induce endoplasmic reticulum stress or cell death reduce this protein. In the present study, the role of PTEN in saturated fatty acid-induced cytotoxicity was examined in H4IIE and HepG2 liver cells. Palmitate and stearate increased the expression of PTEN, whereas the unsaturated fatty acids, oleate and linoleate, reduced PTEN expression in both cell types. SiRNA-mediated knockdown of PTEN did not increase liver cell triglyceride stores or reduce palmitate- or stearate-mediated ER stress or apoptosis. These results suggest that PTEN does not play a significant role in saturated fatty acid-induced cytotoxicity in these liver cell models and in the absence of insulin

Microstructure and mechanical properties of Zr-Cu-Al bulk metallic glasses

Zr49Cu46Al5 and Zr48.5Cu46.5Al5 bulk metallic glasses(BMGs) with diameter of 5 mm were prepared through water-cooled copper mold casting. The phase structures of the two alloys were identified by X-ray diffractometry(XRD). The thermal stability was examined by differential scanning calorimetry(DSC). Zr49Cu46Al5 alloy shows a glass transition temperature, T, of about 689 K, an crystallization temperature, T-x, of about 736 K. The Zr48.5Cu46.5Al5 alloy shows no obvious exothermic peak. The microstructure of the as-cast alloys was analyzed by transmission electron microscopy(TEM). The aggregations of CuZr and CuZr2 nanocrystals with grain size of about 20 nm are observed in Zr49Cu46Al5 nanocrystalline composite, while the Zr48.5Cu46.5Al5 alloy containing many CuZr martensite plates is crystallized seriously. Mechanical properties of bulk Zr49Cu46Al5 nanocrystalline composite and Zr48.5Cu46.5Al5 alloy measured by compression tests at room temperature show that the work hardening ability of Zr48.5Cu46.5Al5 alloy is larger than that of Zr48.5Cu46.5Al5 alloy

Indentation Creep Behavior in Ce-Based Bulk Metallic Glasses at Room Temperature

The room temperature creep behaviors of Ce-based bulk metallic glasses were examined by the use of nanoindentation. The creep rate and creep rate sensitivity of Ce-based BMGs were derived from indentation creep curves. The low creep rate sensitivity of Ce-based BMGs indicates that the room temperature creep is dominated by localized shear flow. The experimental creep curves can be described by a generalized Kelvin model. Furthermore, the creep retardation spectrum is calculated for the Ce-based metallic glasses. The results showed that creep retardation spectrum consists of two relatively separated peaks with the well defined characteristic relaxation times

Compositional Changes of the High-Fat Diet-Induced Gut Microbiota upon Consumption of Common Pulses

The gut microbiome is involved in the host’s metabolism, development, and immunity, which translates to measurable impacts on disease risk and overall health. Emerging evidence supports pulses, i.e., grain legumes, as underutilized nutrient-dense, culinarily versatile, and sustainable staple foods that promote health benefits through modulating the gut microbiota. Herein, the effects of pulse consumption on microbial composition in the cecal content of mice were assessed. Male mice were fed an obesogenic diet formulation with or without 35% of the protein component comprised by each of four commonly consumed pulses—lentil (Lens culinaris L.), chickpea (Cicer arietinum L.), common bean (Phaseolus vulgaris L.), or dry pea (Pisum sativum L.). Mice consuming pulses had distinct microbial communities from animals on the pulse-free diet, as evidenced by β-diversity ordinations. At the phylum level, animals consuming pulses showed an increase in Bacteroidetes and decreases in Proteobacteria and Firmicutes. Furthermore, α-diversity was significantly higher in pulse-fed animals. An ecosystem of the common bacteria that were enhanced, suppressed, or unaffected by most of the pulses was identified. These compositional changes are accompanied by shifts in predicted metagenome functions and are concurrent with previously reported anti-obesogenic physiologic outcomes, suggestive of microbiota-associated benefits of pulse consumption