Metformin and exercise reduce muscle FAT/CD36 and lipid accumulation and blunt the progression of high-fat diet-induced hyperglycemia

Derangements in skeletal muscle fatty acid (FA) metabolism associated with insulin resistance in obesity appear to involve decreased FA oxidation and increased accumulation of lipids such as ceramides and diacylglycerol (DAG). We investigated potential lipid-related mechanisms of metformin (Met) and/or exercise for blunting the progression of hyperglycemia/hyperinsulinemia and skeletal muscle insulin resistance in female Zucker diabetic fatty rats (ZDF), a high-fat (HF) diet-induced model of diabetes. Lean and ZDF rats consumed control or HF diet (48 kcal %fat) alone or with Met (500 mg/kg), with treadmill exercise, or with both exercise and Met interventions for 8 wk. HF-fed ZDF rats developed hyperglycemia (mean: 24.4 +/- 2.1 mM), impairments in muscle insulin-stimulated glucose transport, increases in the FA transporter FAT/CD36, and increases in total ceramide and DAG content. The development of hyperglycemia was significantly attenuated with all interventions, as was skeletal muscle FAT/CD36 abundance and ceramide and DAG content. Interestingly, improvements in insulin-stimulated glucose transport and increased GLUT4 transporter expression in isolated muscle were seen only in conditions that included exercise training. Reduced FA oxidation and increased triacylglycerol synthesis in isolated muscle were observed with all ZDF rats compared with lean rats (P < 0.01) and were unaltered by therapeutic intervention. However, exercise did induce modest increases in peroxisome proliferator-activated receptor-gamma coactivator-1alpha, citrate synthase, and beta-hydroxyacyl-CoA dehydrogenase activity. Thus reduction of skeletal muscle FAT/CD36 and content of ceramide and DAG may be important mechanisms by which exercise training blunts the progression of diet-induced insulin resistance in skeletal muscle.     

Consequences of a Metabolic Glucose-Depletion on the Survival and the Metabolism of Cultured Rat Astrocytes

Neurochemical Research - Brain astrocytes are considered to be highly glycolytic, but these cells also produce ATP via mitochondrial oxidative phosphorylation. To investigate how a metabolic...     

Disentangling community functional components in a litter‐macrodetritivore model system reveals the predominance of the mass ratio hypothesis

Recent investigations have shown that two components of community trait composition are important for key ecosystem processes: (i) the community‐weighted mean trait value (CWM), related to the mass ratio hypothesis and dominant trait values in the community, and (ii) functional diversity (FD), related to the complementarity hypothesis and the divergence of trait values. However, no experiments controlling for the inherent dependence between CWM and FD have been conducted so far. We used a novel experimental framework to disentangle the unique and shared effects of CWM and FD in a leaf litter‐macrodetritivore model system. We manipulated isopod assemblages varying in species number, CWM and FD of litter consumption rate to test the relative contribution of these community parameters in the decomposition process. We showed that CWM, but also the combination of CWM and FD, is a main factor controlling litter decomposition. When we tested individual biodiversity components separately, CWM of litter consumption rate showed a significant effect on decomposition, while FD and species richness alone did not. Our study demonstrated that (i) trait composition rather than species diversity drives litter decomposition, (ii) dominant trait values in the community (CWM) play a chief role in driving ecosystem processes, corroborating the mass ratio hypothesis, and (iii) trait dissimilarity can contribute in modulating the overall biodiversity effects. Future challenge is to assess whether the generality of our finding, that is, that dominant trait values (CWM) predominate over trait dissimilarity (FD), holds for other ecosystem processes, environmental conditions and different spatial and temporal scales.     

Locally resolved membrane binding affinity of the N-terminus of α-synuclein

α-Synuclein is abundantly present in Lewy bodies, characteristic of Parkinson's disease. Its exact physiological role has yet to be determined, but mitochondrial membrane binding is suspected to be a key aspect of its function. Electron paramagnetic resonance spectroscopy in combination with site-directed spin labeling allowed for a locally resolved analysis of the protein-membrane binding affinity for artificial phospholipid membranes, supported by a study of binding to isolated mitochondria. The data reveal that the binding affinity of the N-terminus is nonuniform.     

Comparison of muscle activation levels during arm abduction in the plane of the scapula vs. proprioceptive neuromuscular facilitation upper extremity patterns

This study quantified activation of 8 muscles of the shoulder, trunk, and back during standing performance of (a) arm abduction in the plane of the scapula (scaption), (b) proprioceptive neuromuscular facilitation (PNF) diagonal 1 flexion (D1F), and (c) PNF diagonal 2 flexion (D2F) while lifting a dumbbell with the dominant hand. Twelve men (26.1 ± 4.4 years) and 13 women (24.5 ± 1.9 years) volunteered to participate. Electromyographic signals were collected with DE-3.1 double-differential surface electrodes at a sampling frequency of 1,000 Hz. Electromyographic signals were normalized to peak activity in the maximum voluntary isometric contraction (MVIC) trial and expressed as a percentage. One-way repeated-measures analysis of variance with Bonferroni corrections (α = 0.05) examined muscle activation patterns across the 3 conditions. For the middle trapezius, average activation was greater (p < 0.001) for D2F (70.5 ± 23.4% MVIC) than D1F (46.4 ± 19.6% MVIC). Lower trapezius average activation was greater (p < 0.001) for D2F (55.3 ± 23.8% MVIC) than D1F (40.1 ± 16% MVIC). The anterior deltoid showed greater activation (p = 0.009) for scaption (92.4 ± 26% MVIC) than D1F (74.4 ± 21.4% MVIC). The erector spinae showed greater activation for D2F (34.2 ± 12% MVIC; p < 0.001) and D1F (41.7 ± 21.4% MVIC; p < 0.001) than scaption (14.5 ± 12.3% MVIC). During D2F and scaption, all 6 muscles of the shoulder complex demonstrated very high activation levels (>60% MVIC) with the exception of the lower trapezius (55% MVIC). In contrast, erector spinae and external oblique muscles exhibited moderate activation (21-40% MVIC) during arm elevation. The 6 muscles of the shoulder complex displayed high to very high muscle activation at a level appropriate for strength training during all 3 exercise conditions.     

Insulin-induced translocation of CD36 to the plasma membrane is reversible and shows similarity to that of GLUT4

In cardiac and skeletal muscles, insulin regulates the uptake of long-chain fatty acid (LCFA) via the putative LCFA transporter CD36. Biochemical studies propose an insulin-induced translocation of CD36 from intracellular pools to the plasma membrane (PM), similar to glucose transporter 4 (GLUT4) translocation. To characterize insulin-induced CD36 translocation in intact cells, Chinese hamster ovary (CHO) cells stably expressing CD36 or myc-tagged GLUT4 (GLUT4myc) were created. Immuno-fluorescence microscopy revealed CD36 to be located both intracellularly (in--at least partially--different compartments than GLUT4myc) and at the PM. Upon stimulation with insulin, CD36 translocated to a PM localization similar to that of GLUT4myc; the increase in PM CD36 content, as quantified by surface-protein biotinylation, amounted to 1.7-fold. The insulin-induced CD36 translocation was shown to be phosphatidylinositol-3 kinase-dependent, and reversible (as evidenced by insulin wash-out) in a similar time frame as that for GLUT4. The expression of GLUT4myc in non-stimulated cells, and the insulin-induced increase in PM GLUT4myc correlated with increased deoxyglucose uptake. By contrast, CD36 expression in non-stimulated cells and the insulin-induced increase in PM CD36 were not paralleled by a rise in LCFA uptake, suggesting that in these cells, such increase requires additional proteins, or a protein activation step. Taken together, this study is the first to present morphological evidence for CD36 translocation, and shows this process to resemble GLUT4 translocation.     

Septal pore cap protein SPC18, isolated from the basidiomycetous fungus Rhizoctonia solani, also resides in pore plugs

The hyphae of filamentous fungi are compartmentalized by septa that have a central pore. The fungal septa and septum-associated structures play an important role in maintaining cellular and intrahyphal homeostasis. The dolipore septa in the higher Basidiomycota (i.e., Agaricomycotina) are associated with septal pore caps. Although the ultrastructure of the septal pore caps has been studied extensively, neither the biochemical composition nor the function of these organelles is known. Here, we report the identification of the glycoprotein SPC18 that was found in the septal pore cap-enriched fraction of the basidiomycetous fungus Rhizoctonia solani. Based on its N-terminal sequence, the SPC18 gene was isolated. SPC18 encodes a protein of 158 amino acid residues, which contains a hydrophobic signal peptide for targeting to the endoplasmic reticulum and has an N-glycosylation motif. Immunolocalization showed that SPC18 is present in the septal pore caps. Surprisingly, we also observed SPC18 being localized in some plugs. The data reported here strongly support the hypothesis that septal pore caps are derived from endoplasmic reticulum and are involved in dolipore plugging and, thus, contribute to hyphal homeostasis in basidiomycetous fungi.     

Unique occurrence of pectin-like fibrillar cell wall deposits in xylem fibres of poplar

Using light and electron microscopic techniques, we studied the unique occurrence of fibrillar cell wall deposits in mature xylem fibres from poplar. These cell wall deposits lined the lumen-facing side of the wall, mainly in fibres next to vessel elements. Different lines of evidence point to the pectin-like nature of these fibrillar cell wall deposits. First, specific staining by Alcian Blue 8GX, a dye with high affinity for pectic substances. Second, the strongly reduced staining of the cell wall deposits in microscopic sections treated with pectolytic enzyme. Third, concomitant staining of pits, which are known to consist mainly of pectic substances. Given the pectin-like nature of the fibrillar cell wall deposits as well as their preferred occurrence in fibres neighbouring water-conducting vessel elements, a function for the fibrillar cell wall deposits in lateral water diffusion and stem water storage is hypothesised. The hypothesis is supported by the increased abundance of these cell wall deposits in wood tissue of a drought-sensitive poplar species.     

Cytological study of ischemic damage in rat kidney

Reparative regeneration in different periods following nephrectomy and the application of low-dose radiation has been studied by means of light and electron microscopy. Experimentally induced ischemia resulted in the destruction of renal corpuscles, the perishing of tubular epithelial cells, and the proliferation of connective tissue. Reparative regeneration is based on aseptic inflammation and its phase duration depends on the extent of organ injury. In nephrectomized rats, reparative regeneration is accompanied by necrosis and the deposition of calcium in the cortical substance. Calcium plays an important role in kidney metabolism and its increased content is characteristic of degenerative changes. The experiments showed that the use of low-dose radiation does not accelerate the process of reparative regeneration in rat kidney.