Glucose uptake and glycogen synthesis in normal and chronically active muscles

1993 ◽  
Vol 264 (3) ◽  
pp. E328-E333
Author(s):  
R. J. Talmadge ◽  
H. Silverman

The hindlimb muscles of the C57Bl6J dy2J/dy2J (dy2J) mouse suffer from a chronic neural stimulation (pseudomyotonia), resulting in increased contractile activity. In response to the increased contractile activity, these muscles store increased amounts of glycogen. In this study, glucose uptake and glycogenesis (glycogen synthesis from glucose) were analyzed in chronically active and normal muscles. In vivo experiments demonstrate increased 3-O-methylglucose (3-MG) uptake rates and glycogenesis by chronically active dy2J gastrocnemius muscles (Gast) vs. normal control Gast. The chronically active diaphragm muscle (Dia) showed the highest rates of 3-MG uptake, as well as glycogenesis in vivo when compared with other skeletal muscles. No differences were observed between dy2J and control Dia. The levels of blood glucose were similar between dy2J and control animals. In vitro experiments demonstrated an increased sensitivity and responsiveness to insulin for glucose uptake in the dy2J soleus muscle (Sol). Glycogenesis by dy2J Sol was elevated only at the highest insulin concentration tested (10,000 microU/ml). In contrast, the dy2J extensor digitorum longus muscle had an increased sensitivity and responsiveness to insulin for both glucose uptake and glycogenesis. This study demonstrates that chronically active muscles have elevated capacities for glucose uptake and glycogenesis and may help to explain the elevated glycogen levels in the dy2J hindlimb muscles.

2020 ◽  
pp. 155335062097800
Author(s):  
Ian A. Makey ◽  
Nitin A. Das ◽  
Samuel Jacob ◽  
Magdy M. El-Sayed Ahmed ◽  
Colleen M. Makey ◽  
...  

Background. Retained hemothorax (RH) is a common problem in cardiothoracic and trauma surgery. We aimed to determine the optimum agitation technique to enhance thrombus dissolution and drainage and to apply the technique to a porcine-retained hemothorax. Methods. Three agitation techniques were tested: flush irrigation, ultrasound, and vibration. We used the techniques in a benchtop model with tissue plasminogen activator (tPA) and pig hemothorax with tPA. We used the most promising technique vibration in a pig hemothorax without tPA. Statistics. We used 2-sample t tests for each comparison and Cohen d tests to calculate effect size (ES). Results. In the benchtop model, mean drainages in the agitation group and control group and the ES were flush irrigation, 42%, 28%, and 2.91 ( P = .10); ultrasound, 35%, 27%, and .76 ( P = .30); and vibration, 28%, 19%, and 1.14 ( P = .04). In the pig hemothorax with tPA, mean drainages and the ES of each agitation technique compared with control (58%) were flush irrigation, 80% and 1.14 ( P = .37); ultrasound, 80% and 2.11 ( P = .17); and vibration, 95% and 3.98 ( P = .06). In the pig hemothorax model without tPA, mean drainages of the vibration technique and control group were 50% and 43% (ES = .29; P = .65). Discussion. In vitro studies suggested flush irrigation had the greatest effect, whereas only vibration was significantly different vs the respective controls. In vivo with tPA, vibration showed promising but not statistically significant results. Results of in vivo experiments without tPA were negative. Conclusion. Agitation techniques, in combination with tPA, may enhance drainage of hemothorax.


2001 ◽  
Vol 21 (5) ◽  
pp. 1633-1646 ◽  
Author(s):  
Tsutomu Wada ◽  
Toshiyasu Sasaoka ◽  
Makoto Funaki ◽  
Hiroyuki Hori ◽  
Shihou Murakami ◽  
...  

ABSTRACT Phosphatidylinositol (PI) 3-kinase plays an important role in various metabolic actions of insulin including glucose uptake and glycogen synthesis. Although PI 3-kinase primarily functions as a lipid kinase which preferentially phosphorylates the D-3 position of phospholipids, the effect of hydrolysis of the key PI 3-kinase product PI 3,4,5-triphosphate [PI(3,4,5)P3] on these biological responses is unknown. We recently cloned rat SH2-containing inositol phosphatase 2 (SHIP2) cDNA which possesses the 5′-phosphatase activity to hydrolyze PI(3,4,5)P3 to PI 3,4-bisphosphate [PI(3,4)P2] and which is mainly expressed in the target tissues of insulin. To study the role of SHIP2 in insulin signaling, wild-type SHIP2 (WT-SHIP2) and 5′-phosphatase-defective SHIP2 (ΔIP-SHIP2) were overexpressed in 3T3-L1 adipocytes by means of adenovirus-mediated gene transfer. Early events of insulin signaling including insulin-induced tyrosine phosphorylation of the insulin receptor β subunit and IRS-1, IRS-1 association with the p85 subunit, and PI 3-kinase activity were not affected by expression of either WT-SHIP2 or ΔIP-SHIP2. Because WT-SHIP2 possesses the 5′-phosphatase catalytic region, its overexpression marked by decreased insulin-induced PI(3,4,5)P3 production, as expected. In contrast, the amount of PI(3,4,5)P3 was increased by the expression of ΔIP-SHIP2, indicating that ΔIP-SHIP2 functions in a dominant-negative manner in 3T3-L1 adipocytes. Both PI(3,4,5)P3 and PI(3,4)P2 were known to possibly activate downstream targets Akt and protein kinase Cλ in vitro. Importantly, expression of WT-SHIP2 inhibited insulin-induced activation of Akt and protein kinase Cλ, whereas these activations were increased by expression of ΔIP-SHIP2 in vivo. Consistent with the regulation of downstream molecules of PI 3-kinase, insulin-induced 2-deoxyglucose uptake and Glut4 translocation were decreased by expression of WT-SHIP2 and increased by expression of ΔIP-SHIP2. In addition, insulin-induced phosphorylation of GSK-3β and activation of PP1 followed by activation of glycogen synthase and glycogen synthesis were decreased by expression of WT-SHIP2 and increased by the expression of ΔIP-SHIP2. These results indicate that SHIP2 negatively regulates metabolic signaling of insulin via the 5′-phosphatase activity and that PI(3,4,5)P3 rather than PI(3,4)P2 is important for in vivo regulation of insulin-induced activation of downstream molecules of PI 3-kinase leading to glucose uptake and glycogen synthesis.


Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 3567-3567
Author(s):  
Tatiana Ulyanova ◽  
Gregory V. Priestley ◽  
Yi Jiang ◽  
Stephen Padilla ◽  
Thalia Papayannopoulou

Abstract Previous experiments in vitro have emphasized the important role of a5b1 integrin/fibronectin interactions in terminal stages of erythroid differentiation (JCB1987, 105:3105), whereas in vivo experiments with genetically deficient mice (JI2000, 165:4667) and recent in vitro ones emphasized the important contribution of a4b1 integrin in the expansion of fetal erythroid progenitors (JCB2007, 177:871) or for optimal responses post stress in adult animals (MCB2003, 23:9349). However, no abnormalities in erythropoiesis were reported in a model of conditional ablation of b1 integrins post-transplantation (Blood2006, 108:1857). Therefore, it has not been clear to what extent each of the two major b1 integrins (a4b1 and a5b1) alone or in combination is critical for expansion and/or terminal erythroid differentiation of adult cells at homeostasis and/or after stress. We have made detailed and parallel observations comparing erythropoiesis in two genetic models with conditional ablation of b1 or a4 integrins at homeostasis and after phenylhydrazine (PHZ)-mediated stress. Basal erythropoiesis in b1-, a4-deficient and control mice as assessed by hematocrit levels and total nucleated erythroid cells (Ter119+) in BM and spleen was similar. Furthermore, both b1 and a4-deficient mice showed an increase in circulating progenitors (1275±230 CFC/ml PB, 2446±256 CFC/ml PB, respectively) over controls (338±113 CFC/ml PB). However, post PHZ-induced hemolytic stress there was a dramatic difference in outcomes of b1-deficient, but modest differences in a4-deficient mice compared to controls. Survival of b1-deficient mice by day 6 post PHZ was 33% compared to 100% in a4-deficient and control groups. In b1-deficient animals, no significant increase in spleen cellularity (153±26×106 and194±64×106 cells/spleen at day 0 and 6 post PHZ, respectively) was detected and the expansion of total erythroid precursors (CD71hi,Ter119+) in the spleen was minimal (from 2.08×106 to 10.8×106 cells/spleen at day 6). In contrast, in a4-deficient and control mice by the same time spleen cellularity increased respectively by 3 and 8 fold, and erythroid precursors expanded by 400 and 2,500 fold. Of interest, BM response to PHZ was not significantly different among all groups. To test whether the splenic response was cell-autonomous or environmentally controlled we compared PHZ response in wild type recipients reconstituted with b1-ablated (Cre+b1D/D) or with control (Cre-b1f/f) BM cells. Recipients of b1-ablated cells had an impaired response compared to recipients of control cells, which was somewhat intermediate to that seen in non-transplanted b1-deficient animals; by day 6 post PHZ, spleen cellularity was 300±24×106 cells/spleen and erythroid precursors expanded by 130 fold in recipients of b1-ablated BM cells compared to 859±159×106 cells/spleen and 900 fold precursor increase in control recipients. These data suggest that both erythroid and their environmental cells were responsible for the reduced survival and poor spleen response in b1-deficient mice. The target environmental cells (fibroblasts, endothelial cells, macrophages) and/or matrix involved will be the focus of future studies. It is of interest that in contrast to splenic response, the increased release of progenitors from BM seen in animals reconstituted with b1D/D cells was as high as that seen in non-transplanted b1- deficient animals and with the same qualitative characteristics, suggesting this alteration in biodistribution of progenitors is cell autonomous. Taken together, our data suggest that a combined expression of b1 integrins in erythroid and cells in their microenvironment is critical for survival and optimal splenic response to a PHZ-induced stress in adult mice; release of progenitors seen at homeostasis in both b1 and a4 models is cell autonomous with a preferential erythroid progenitor release from BM seen only in b1-deficient but not in a4-deficient mice; in contrast to results with fetal liver cells showing a critical role of a4b1 but not a5b1 integrin for proliferative expansion of erythroid cells, in adults a5b1 expression in erythroid and environmental cells in the spleen assumes a more critical role. Our data expand the current knowledge on the distinct dependency of a4b1 vs a5b1 integrins in basal vs stress erythropoiesis and bridge previously divergent information from in vitro and in vivo experiments.


1980 ◽  
Vol 239 (3) ◽  
pp. R326-R331
Author(s):  
S. A. Halbert ◽  
R. J. Bourdage ◽  
J. L. Boling ◽  
J. A. Ringo ◽  
R. J. Blandau

An optoelectronic instrument to record oviductal muscular activity in chronically instrumented animals was evaluated in in vitro and in vivo experiments. The intensity of red light transmitted through the oviduct was modulated by contractions of the oviductal wall producing an optical analog of the mechanical events. Accuracy of the analog was tested by Fourier analysis of signals from mechanical and optoelectronic transducers placed at the same site on the oviduct; the results validated the use of the optical device as a contraction event sensor. Contractions of the tubal mesenteries had less effect on the optical signal than on signals from extraluminal mechanical transducers. Optical and photographic recordings of luminal transport in exposed oviducts showed a correspondence of intraluminal movements to events in the optical contraction signal. This instrument does not alter tubal function, and thus it is an especially useful experimental tool to investigate the role of oviductal muscular activity in fertility.


2018 ◽  
Vol 1 (2) ◽  
pp. 96-103 ◽  
Author(s):  
John M. McPartland ◽  
Steve G. Naraine

The mechanism by which Cannabis sativa dispersed from its center of origin remains an open question. The literature provides many hypotheses, which we review for the first time, but experiments are few. Darwin was interested in zoochory – the transport of plants by animals. He demonstrated endozoochory (transport of seeds via animal digestive systems) of C. sativa achenes (seeds) by carrier pigeons, but he did not quantify achene survival rates. We assessed mammalian endozoochory in a triplicate experiment: feeding C. sativa achenes into a simulated gastrointestinal system, a dog, and a human. The in vitro system subjected achenes to sequential digestive enzymes. Achenes were planted in potting soil and monitored for emergence under growroom conditions. The in vivo experiments added achenes to a normal morning meal (dog food or granola). Feces were collected for daily instillation into an outdoor garden and monitored for seedling emergence for 16 days. Control achenes were planted directly into soil without ingestion. In the in vitro study, 34.7% of the digested achenes emerged as seedlings. The in vivo emergence rates were 10.3, 1.3, and 76.0% for the dog, human, and control conditions. The three groups differed significantly (χ2 = 1,264.93, p < 0.0001). Achene survival was greatest under in vitro conditions, which lacked a mastication step, compared to dog (minimal chewing) and human (maximal chewing) conditions. Although C. sativa lacks evolutionary traits for classic endozoochory (i.e., a fleshy fruit), it seems well adapted to this manner of seed dispersal.


1992 ◽  
Vol 263 (3) ◽  
pp. E556-E561 ◽  
Author(s):  
R. R. Russell ◽  
V. T. Nguyen ◽  
J. M. Mrus ◽  
H. Taegtmeyer

We have previously reported that the nutritional state in vivo results in differential insulin responses by the perfused heart in vitro. To further assess the effects of insulin on glucose uptake at physiological work loads, hearts from fed and fasted (16-20 h) rats were perfused with buffer containing 2-[18F]fluoro-2-deoxy-D-glucose (2-FDG) and glucose (10 mM) alone or plus lactate (10 mM) as a competing substrate, with insulin (10 mU/ml) added after a control period. When glucose was the only substrate, the addition of insulin decreased the fractional rate of 2-FDG uptake in hearts from either fed or fasted rats. The effect of insulin on increasing myocardial 2-FDG uptake was immediate and sustained only in hearts from fasted rats in the presence of lactate, despite no change in cardiac work. At the same time, the increase in 2-FDG uptake and phosphorylation was associated with an increase in the tissue content of glycogen in hearts from fasted rats. We conclude that lactate unmasks insulin sensitivity in heart muscle at physiological work loads but that this unmasking of insulin-mediated glucose uptake is dependent on the nutritional state of the animal. The glucose up as a result of insulin stimulation is preferentially utilized for glycogen repletion and does not enter the glycolytic pathway. This observation also suggests that myocardial glycogen synthesis in vitro is affected by the nutritional state in vivo and that lactate provides a substrate for oxidative phosphorylation while glucose is preferentially utilized for glycogen synthesis.


1991 ◽  
Vol 275 (2) ◽  
pp. 477-483 ◽  
Author(s):  
P A MacLennan ◽  
A McArdle ◽  
R H Edwards

1. mdx mice do not express dystrophin, the product of the gene which is defective in Duchenne and Becker muscular dystrophy. We have previously shown that protein-synthetic rates (ks) are increased in mdx mouse muscles [MacLennan & Edwards (1990) Biochem. J. 268, 795-797]. 2. The tumour-promoting stereoisomer of phorbol 12,13-didecanoate (4 beta-PDD) acutely increased the ks of muscles from mdx and wild-type (C57BL/10) mice incubated in vitro in the absence of insulin. The effects of 4 beta-PDD are presumably mediated by activation of protein kinase C (PKC). 3. The muscle glycogen concentrations of mdx mice were higher than those of C57BL/10 mice. Studies performed in vivo and in vitro suggested that the effect might be at least partially due to increased rate of glycogen synthesis in mdx muscle. 4. 4 beta-PDD increased the glycogen-synthetic rates rates of C57BL/10, but not mdx, muscles incubated in vitro in the absence of insulin. 5. In muscles from both species incubated in the absence of insulin, treatment with 4 beta-PDD also induced increased rates of glucose uptake and lactate production. Kinetic studies of C57BL/10 and mdx muscles suggested that 4 beta-PDD raised the Vmax. of glucose uptake, but did not alter the Km for the process. 6. The possible role of PKC in controlling the protein and carbohydrate metabolism of normal and mdx mouse muscles is discussed.


2021 ◽  
Vol 10 (1) ◽  
pp. 18
Author(s):  
Po-Kai Pan ◽  
Tsung-Meng Wu ◽  
Chiu-Ming Wen ◽  
Yin-Yu Chen ◽  
Yu-Sheng Wu

Sarcodia suieae acetyl-xylogalactan was reported to induce macrophage polarisation, and could positively regulate macrophage activation. In this study, we evaluated the effect of Sarcodia suieae acetyl-xylogalactan on the Nile tilapia. First, we assessed the influence of acetyl-xylogalactan on the survival, glucose uptake, and phagocytic activity of tilapia head kidney (THK) melanomacrophage, and observed increased proliferation of these cells in the MTT assay after 12 and 24 h of treatment. Glucose uptake increased in THK melanomacrophage treated with 20 and 30 μg acetyl-xylogalactan for 24 h. Their phagocytic activity was positively enhanced following exposure to acetyl-xylogalactan. Nile tilapia were fed with acetyl-xylogalactan for 4 weeks. At the end of the experiment, Nile tilapia were sacrificed, and the lipopolysaccharide-induced liver and head-kidney apoptosis was examined under reducing conditions in comparison with controls. The phagocytic activities of liver and head-kidney cells were enhanced after 4 weeks of feeding. Blood biochemical analysis revealed a reduction in glutamic oxaloacetic transaminase (GOT) and glutamic pyruvic transaminase (GPT) levels after 4 weeks of feeding. Combined with in vitro and in vivo experiments results, the extracted S. suieae acetyl-xylogalactan could directly induce THK melanomacrophage proliferation, glucose uptake, and phagocytic activity. Acetyl-xylogalactan was able to induce Nile tilapia liver and head-kidney resident macrophage activity, and reduced LPS-induced liver and head-kidney cell apoptosis. S. suieae acetyl-xylogalactan may modulate Nile tilapia macrophage activation by polarising them into M1 macrophages to improve the Nile tilapia nonspecific immune response.


2018 ◽  
Vol 2018 ◽  
pp. 1-15 ◽  
Author(s):  
Ching-Ping Yang ◽  
Ming-Yuh Shiau ◽  
Yi-Ren Lai ◽  
Kuo-Ting Ho ◽  
Chiao-Wan Hsiao ◽  
...  

Type 2 diabetes mellitus (T2DM), with dysregulated hepatic gluconeogenesis as the major cause of fasting hyperglycemia, is closely associated with chronic inflammation. We previously demonstrated interleukin-4 (IL-4) improves insulin sensitivity and glucose tolerance while reducing lipid deposits. The present study examined the in vitro effects of IL-4 on insulin signaling molecules, glucose uptake, and lipid metabolism in hepatocytes, as well as in vivo effects on hepatic adiposity, for elucidating the roles of IL-4 in hepatic energy metabolism. Potential interaction between IL-4 and insulin in regulating hepatic metabolism was also investigated. Our results showed that IL-4 enhanced Akt and GSK-3α/β phosphorylations, which in turn promoted glycogen synthesis. IL-4 not only potentiated basal glucose uptake by upregulating glucose transporter 2 expression but also promoted insulin-induced glucose uptake. Additionally, IL-4 increased triglyceride contents through facilitating free fatty acid uptake and expression/activity of lipogenic enzymes. The major effects of IL-4 on the liver were to promote energy storage by boosting insulin-stimulated glucose uptake and lipid synthesis. This study provides evidence to implicate the novel roles of IL-4 in mediating hepatic glucose and lipid metabolism, interactions between immune responses and metabolic homeostasis, and the involvement of IL-4 in metabolic abnormalities.


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