Initiating aerobic exercise with low glycogen content reduces markers of myogenesis but not mTORC1 signaling.

BACKGROUND: The effects of low muscle glycogen on molecular markers of protein synthesis and myogenesis before and during aerobic exercise with carbohydrate ingestion is unclear. The purpose of this study was to determine the effects of initiating aerobic exercise with low muscle glycogen on mTORC1 signaling and markers of myogenesis. METHODS: Eleven men completed two cycle ergometry glycogen depletion trials separated by 7-d, followed by randomized isocaloric refeeding for 24-h to elicit low (LOW; 1.5 g/kg carbohydrate, 3.0 g/kg fat) or adequate (AD; 6.0 g/kg carbohydrate, 1.0 g/kg fat) glycogen. Participants then performed 80-min of cycle ergometry (64 ± 3% VO2peak) while ingesting 146 g carbohydrate. mTORC1 signaling (Western blotting) and gene transcription (RT-qPCR) were determined from vastus lateralis biopsies before glycogen depletion (baseline, BASE), and before (PRE) and after (POST) exercise. RESULTS: Regardless of treatment, p-mTORC1Ser2448, p-p70S6KSer424/421, and p-rpS6Ser235/236 were higher (P < 0.05) POST compared to PRE and BASE. PAX7 and MYOGENIN were lower (P < 0.05) in LOW compared to AD, regardless of time, while MYOD was lower (P < 0.05) in LOW compared to AD at PRE, but not different at POST. CONCLUSION: Initiating aerobic exercise with low muscle glycogen does not affect mTORC1 signaling, yet reductions in gene expression of myogenic regulatory factors suggest that muscle recovery from exercise may be reduced.

A 3-day dietary manipulation affects muscle glycogen and results in modifications of carbohydrate and fat metabolism during exercise when hyperglycaemic.

PURPOSE: The effect of hyperglycaemia on exercise with low and elevated muscle glycogen on glucose utilization (GUR), carbohydrate and fat oxidation, hormonal and metabolite responses, as well as rating of perceived exertion (RPE) were explored. METHODS: Five healthy trained males were exercised for 90 min at 70% V̇O2max in two trials, while glucose was infused intravenously at rates to "clamp" blood glucose at 12 mM. On one occasion, participants were 'loaded' with carbohydrate (CHO-L), whilst on a separate occasion, participants were glycogen depleted (CHO-D). Prior exercise and dietary manipulations produced the 'loaded' and 'depleted' states. RESULTS: The CHO-L and CHO-D conditions resulted in muscle glycogen concentrations of 377 and 159 mmol/g dw, respectively. Hyperglycaemia elevated plasma insulin concentrations with higher levels for CHO-L than for CHO-D (P < 0.01). Conversely, CHO-D elevated plasma adrenaline and noradrenaline higher than CHO-L (P < 0.05). Plasma fat metabolites (NEFA, ß-hydroxybutyrate, and glycerol) were higher under CHO-D than CHO-L (P < 0.01). The resultant was that the rates of total carbohydrate and fat oxidation were elevated and depressed for loaded CHO-L vs CHO-D respectively (P < 0.01), although no difference was found for GUR (P > 0.05). The RPE over the exercise period was higher for CHO-D than CHO-L (P < 0.05). CONCLUSION: Hyperglycaemia during exercise, when muscle glycogen is reduced, attenuates insulin but promotes catecholamines and fat metabolites. The effect is a subsequent elevation of fat oxidation, a reduction in CHO oxidation without a concomitant increase in GUR, and an increase in RPE.

Single-Cell Analysis for Glycogen Localization and Metabolism in Cultured Astrocytes.

Cerebral glycogen is principally localized in astrocytes rather than in neurons. Glycogen metabolism has been implicated in higher brain functions, including learning and memory, yet the distribution patterns of glycogen in different types of astrocytes have not been fully described. Here, we applied a method based on the incorporation of 2-NBDG, a D-glucose fluorescent derivative that can trace glycogen, to investigate glycogen's distribution in the brain. We identified two types of astrocytes, namely, 2-NBDGI (glycogen-deficient) and 2-NBDGII (glycogen-rich) cells. Whole-cell patch-clamp and fluorescence-activated cell sorting (FACS) were used to separate 2-NBDGII astrocytes from 2-NBDGI astrocytes. The expression levels of glycogen metabolic enzymes were analyzed in 2-NBDGI and 2-NBDGII astrocytes. We found unique glycogen metabolic patterns between 2-NBDGI and 2-NBDGII astrocytes. We also observed that 2-NBDGII astrocytes were mainly identified as fibrous astrocytes but not protoplasmic astrocytes. Our data reveal cell type-dependent glycogen distribution and metabolism patterns, suggesting diverse functions of these different astrocytes.

Retinal ischemia induces α-SMA-mediated capillary pericyte contraction coincident with perivascular glycogen depletion.

Increasing evidence indicates that pericytes are vulnerable cells, playing pathophysiological roles in various neurodegenerative processes. Microvascular pericytes contract during cerebral and coronary ischemia and do not relax after re-opening of the occluded artery, causing incomplete reperfusion. However, the cellular mechanisms underlying ischemia-induced pericyte contraction, its delayed emergence, and whether it is pharmacologically reversible are unclear. Here, we investigate i) whether ischemia-induced pericyte contractions are mediated by alpha-smooth muscle actin (α-SMA), ii) the sources of calcium rise in ischemic pericytes, and iii) if peri-microvascular glycogen can support pericyte metabolism during ischemia. Thus, we examined pericyte contractility in response to retinal ischemia both in vivo, using adaptive optics scanning light ophthalmoscopy and, ex vivo, using an unbiased stereological approach. We found that microvascular constrictions were associated with increased calcium in pericytes as detected by a genetically encoded calcium indicator (NG2-GCaMP6) or a fluoroprobe (Fluo-4). Knocking down α-SMA expression with RNA interference or fixing F-actin with phalloidin or calcium antagonist amlodipine prevented constrictions, suggesting that constrictions resulted from calcium- and α-SMA-mediated pericyte contractions. Carbenoxolone or a Cx43-selective peptide blocker also reduced calcium rise, consistent with involvement of gap junction-mediated mechanisms in addition to voltage-gated calcium channels. Pericyte calcium increase and capillary constrictions became significant after 1 h of ischemia and were coincident with depletion of peri-microvascular glycogen, suggesting that glucose derived from glycogen granules could support pericyte metabolism and delay ischemia-induced microvascular dysfunction. Indeed, capillary constrictions emerged earlier when glycogen breakdown was pharmacologically inhibited. Constrictions persisted despite recanalization but were reversible with pericyte-relaxant adenosine administered during recanalization. Our study demonstrates that retinal ischemia, a common cause of blindness, induces α-SMA- and calcium-mediated persistent pericyte contraction, which can be delayed by glucose driven from peri-microvascular glycogen. These findings clarify the contractile nature of capillary pericytes and identify a novel metabolic collaboration between peri-microvascular end-feet and pericytes.

Oral ethinylestradiol-levonorgestrel normalizes fructose-induced hepatic lipid accumulation and glycogen depletion in female rats.

The present study investigated the effects of oral ethinylestradiol-levonorgestrel (EEL) on hepatic lipid and glycogen contents during high fructose (HF) intake, and determined whether pyruvate dehydrogenase kinase-4 (PDK-4) and glucose-6-phosphate dehydrogenase (G6PD) activity were involved in HF and (or) EEL-induced hepatic dysmetabolism. Female Wistar rats weighing 140-160 g were divided into groups. The control, EEL, HF, and EEL+HF groups received water (vehicle, p.o.), 1.0 µg ethinylestradiol plus 5.0 µg levonorgestrel (p.o.), fructose (10% w/v), and EEL plus HF, respectively, on a daily basis for 8 weeks. Results revealed that treatment with EEL or HF led to insulin resistance, hyperinsulinemia, increased hepatic uric acid production and triglyceride content, reduced glycogen content, and reduced production of plasma or hepatic glutathione- and G6PD-dependent antioxidants. HF but not EEL also increased fasting glucose and hepatic PDK-4. Nonetheless, these alterations were attenuated by EEL in HF-treated rats. Our results demonstrate that hepatic lipid accumulation and glycogen depletion induced by HF is accompanied by increased PDK-4 and defective G6PD activity. The findings also suggest that EEL would attenuate hepatic lipid accumulation and glycogen depletion by suppression of PDK-4 and enhancement of a G6PD-dependent antioxidant barrier.

Low pre-exercise muscle glycogen availability offsets the effect of post-exercise cold water immersion in augmenting PGC-1α gene expression.

We assessed the effects of post-exercise cold-water immersion (CWI) in modulating PGC-1α mRNA expression in response to exercise commenced with low muscle glycogen availability. In a randomized repeated-measures design, nine recreationally active males completed an acute two-legged high-intensity cycling protocol (8 × 5 min at 82.5% peak power output) followed by 10 min of two-legged post-exercise CWI (8°C) or control conditions (CON). During each trial, one limb commenced exercise with low (LOW: <300 mmol·kg-1 dw) or very low (VLOW: <150 mmol·kg-1 dw) pre-exercise glycogen concentration, achieved via completion of a one-legged glycogen depletion protocol undertaken the evening prior. Exercise increased (P < 0.05) PGC-1α mRNA at 3 h post-exercise. Very low muscle glycogen attenuated the increase in PGC-1α mRNA expression compared with the LOW limbs in both the control (CON VLOW ~3.6-fold vs. CON LOW ~5.6-fold: P = 0.023, ES 1.22 Large) and CWI conditions (CWI VLOW ~2.4-fold vs. CWI LOW ~8.0 fold: P = 0.019, ES 1.43 Large). Furthermore, PGC-1α mRNA expression in the CWI-LOW trial was not significantly different to the CON LOW limb (P = 0.281, ES 0.67 Moderate). Data demonstrate that the previously reported effects of post-exercise CWI on PGC-1α mRNA expression (as regulated systemically via ß-adrenergic mediated cell signaling) are offset in those conditions in which local stressors (i.e., high-intensity exercise and low muscle glycogen availability) have already sufficiently activated the AMPK-PGC-1α signaling axis. Additionally, data suggest that commencing exercise with very low muscle glycogen availability attenuates PGC-1α signaling.

Lack of liver glycogen causes hepatic insulin resistance and steatosis in mice.

Disruption of the Gys2 gene encoding the liver isoform of glycogen synthase generates a mouse strain (LGSKO) that almost completely lacks hepatic glycogen, has impaired glucose disposal, and is pre-disposed to entering the fasted state. This study investigated how the lack of liver glycogen increases fat accumulation and the development of liver insulin resistance. Insulin signaling in LGSKO mice was reduced in liver, but not muscle, suggesting an organ-specific defect. Phosphorylation of components of the hepatic insulin-signaling pathway, namely IRS1, Akt, and GSK3, was decreased in LGSKO mice. Moreover, insulin stimulation of their phosphorylation was significantly suppressed, both temporally and in an insulin dose response. Phosphorylation of the insulin-regulated transcription factor FoxO1 was somewhat reduced and insulin treatment did not elicit normal translocation of FoxO1 out of the nucleus. Fat overaccumulated in LGSKO livers, showing an aberrant distribution in the acinus, an increase not explained by a reduction in hepatic triglyceride export. Rather, when administered orally to fasted mice, glucose was directed toward hepatic lipogenesis as judged by the activity, protein levels, and expression of several fatty acid synthesis genes, namely, acetyl-CoA carboxylase, fatty acid synthase, SREBP1c, chREBP, glucokinase, and pyruvate kinase. Furthermore, using cultured primary hepatocytes, we found that lipogenesis was increased by 40% in LGSKO cells compared with controls. Of note, the hepatic insulin resistance was not associated with increased levels of pro-inflammatory markers. Our results suggest that loss of liver glycogen synthesis diverts glucose toward fat synthesis, correlating with impaired hepatic insulin signaling and glucose disposal.

Motor unit and muscle fiber type grouping after peripheral nerve injury in the rat.

Muscle unit (MU) fibers innervated by one motoneuron and corresponding muscle fiber types are normally distributed in a mosaic. We asked whether, 4-8months after common peroneal nerve transection and random surgical alignment of nerve stumps in rat tibialis anterior muscles 1) reinnervated MU muscle and muscle fiber type clumping is invariant and 2) slow and fast motoneurons regenerate their nerve fibers within original endoneurial pathways. MU contractile forces were recorded in vivo, the MUs classified into types according to their contractile speed and fatigability, and one MU subjected to alternate exhaustive stimulation-recovery cycles to deplete glycogen for histochemical MU fiber recognition and enumeration, and muscle fiber typing. MU muscle fibers occupied defined territories whose size increased with MU force and muscle fiber numbers in normal and reinnervated muscles. The reinnervated MU muscle fiber territories were significantly smaller, the fibers clumped within 1-3 groups in 90% of the MUs, and each fiber lying adjacent to another significantly more frequently. Most reinnervated slow muscle fibers were normally located in the deep muscle compartment but substantial numbers were located abnormally in the superficial compartment. Our findings that well reinnervated muscle fibers clump in small muscles contrast with our earlier findings of clumping in large muscles only when reinnervated MU numbers were significantly reduced. We conclude that fiber type clumping is predictive of muscle reinnervation in small but not large muscles. In the latter muscles, clumping is more indicative of sprouting after partial nerve injuries than of muscle reinnervation after complete nerve injuries.

Dynamics of Photosynthesis in a Glycogen-Deficient glgC Mutant of Synechococcus sp. Strain PCC 7002.

Cyanobacterial glycogen-deficient mutants display impaired degradation of light-harvesting phycobilisomes under nitrogen-limiting growth conditions and secrete a suite of organic acids as a putative reductant-spilling mechanism. This genetic background, therefore, represents an important platform to better understand the complex relationships between light harvesting, photosynthetic electron transport, carbon fixation, and carbon/nitrogen metabolisms. In this study, we conducted a comprehensive analysis of the dynamics of photosynthesis as a function of reductant sink manipulation in a glycogen-deficient glgC mutant of Synechococcus sp. strain PCC 7002. The glgC mutant showed increased susceptibility to photoinhibition during the initial phase of nitrogen deprivation. However, after extended periods of nitrogen deprivation, glgC mutant cells maintained higher levels of photosynthetic activity than the wild type, supporting continuous organic acid secretion in the absence of biomass accumulation. In contrast to the wild type, the glgC mutant maintained efficient energy transfer from phycobilisomes to photosystem II (PSII) reaction centers, had an elevated PSII/PSI ratio as a result of reduced PSII degradation, and retained a nitrogen-replete-type ultrastructure, including an extensive thylakoid membrane network, after prolonged nitrogen deprivation. Together, these results suggest that multiple global signals for nitrogen deprivation are not activated in the glgC mutant, allowing the maintenance of active photosynthetic complexes under conditions where photosynthesis would normally be abolished.

Deficiency of the BiP cochaperone ERdj4 causes constitutive endoplasmic reticulum stress and metabolic defects.

Endoplasmic reticulum-localized DnaJ 4 (ERdj4) is an immunoglobulin-binding protein (BiP) cochaperone and component of the endoplasmic reticulum-associated degradation (ERAD) pathway that functions to remove unfolded/misfolded substrates from the ER lumen under conditions of ER stress. To elucidate the function of ERdj4 in vivo, we disrupted the ERdj4 locus using gene trap (GT) mutagenesis, leading to hypomorphic expression of ERdj4 in mice homozygous for the trapped allele (ERdj4(GT/GT)). Approximately half of ERdj4(GT/GT) mice died perinatally associated with fetal growth restriction, reduced hepatic glycogen stores, and hypoglycemia. Surviving adult mice exhibited evidence of constitutive ER stress in multiple cells/tissues, including fibroblasts, lung, kidney, salivary gland, and pancreas. Elevated ER stress in pancreatic ß cells of ERdj4(GT/GT) mice was associated with ß cell loss, hypoinsulinemia, and glucose intolerance. Collectively these results suggest an important role for ERdj4 in maintaining ER homeostasis during normal fetal growth and postnatal adaptation to metabolic stress.

Exercise with low glycogen increases PGC-1α gene expression in human skeletal muscle.

Recent studies suggest that carbohydrate restriction can improve the training-induced adaptation of muscle oxidative capacity. However, the importance of low muscle glycogen on the molecular signaling of mitochondrial biogenesis remains unclear. Here, we compare the effects of exercise with low (LG) and normal (NG) glycogen on different molecular factors involved in the regulation of mitochondrial biogenesis. Ten highly trained cyclists (VO(2max) 65 ± 1 ml/kg/min, W max 387 ± 8 W) exercised for 60 min at approximately 64 % VO(2max) with either low [166 ± 21 mmol/kg dry weight (dw)] or normal (478 ± 33 mmol/kg dw) muscle glycogen levels achieved by prior exercise/diet intervention. Muscle biopsies were taken before, and 3 h after, exercise. The mRNA of peroxisome proliferator-activated receptor-γ coactivator-1 was enhanced to a greater extent when exercise was performed with low compared with normal glycogen levels (8.1-fold vs. 2.5-fold increase). Cytochrome c oxidase subunit I and pyruvate dehydrogenase kinase isozyme 4 mRNA were increased after LG (1.3- and 114-fold increase, respectively), but not after NG. Phosphorylation of AMP-activated protein kinase, p38 mitogen-activated protein kinases and acetyl-CoA carboxylase was not changed 3 h post-exercise. Mitochondrial reactive oxygen species production and glutathione oxidative status tended to be reduced 3 h post-exercise. We conclude that exercise with low glycogen levels amplifies the expression of the major genetic marker for mitochondrial biogenesis in highly trained cyclists. The results suggest that low glycogen exercise may be beneficial for improving muscle oxidative capacity.

Loss of the starvation-induced gene Rack1 leads to glycogen deficiency and impaired autophagic responses in Drosophila.

Autophagy delivers cytoplasmic material for lysosomal degradation in eukaryotic cells. Starvation induces high levels of autophagy to promote survival in the lack of nutrients. We compared genome-wide transcriptional profiles of fed and starved control, autophagy-deficient Atg7 and Atg1 null mutant Drosophila larvae to search for novel regulators of autophagy. Genes involved in catabolic processes including autophagy were transcriptionally upregulated in all cases. We also detected repression of genes involved in DNA replication in autophagy mutants compared with control animals. The expression of Rack1 (receptor of activated protein kinase C 1) increased 4.1- to 5.5-fold during nutrient deprivation in all three genotypes. The scaffold protein Rack1 plays a role in a wide range of processes including translation, cell adhesion and migration, cell survival and cancer. Loss of Rack1 led to attenuated autophagic response to starvation, and glycogen stores were decreased 11.8-fold in Rack1 mutant cells. Endogenous Rack1 partially colocalized with GFP-Atg8a and early autophagic structures on the ultrastructural level, suggesting its involvement in autophagosome formation. Endogenous Rack1 also showed a high degree of colocalization with glycogen particles in the larval fat body, and with Shaggy, the Drosophila homolog of glycogen synthase kinase 3B (GSK-3B). Our results, for the first time, demonstrated the fundamental role of Rack1 in autophagy and glycogen synthesis.

Training with low muscle glycogen enhances fat metabolism in well-trained cyclists.

PURPOSE: To determine the effects of training with low muscle glycogen on exercise performance, substrate metabolism, and skeletal muscle adaptation. METHODS: Fourteen well-trained cyclists were pair-matched and randomly assigned to HIGH- or LOW-glycogen training groups. Subjects performed nine aerobic training (AT; 90 min at 70% VO2max) and nine high-intensity interval training sessions (HIT; 8 × 5-min efforts, 1-min recovery) during a 3-wk period. HIGH trained once daily, alternating between AT on day 1 and HIT the following day, whereas LOW trained twice every second day, first performing AT and then, 1 h later, performing HIT. Pretraining and posttraining measures were a resting muscle biopsy, metabolic measures during steady-state cycling, and a time trial. RESULTS: Power output during HIT was 297 ± 8 W in LOW compared with 323 ± 9 W in HIGH (P < 0.05); however, time trial performance improved by ∼10% in both groups (P < 0.05). Fat oxidation during steady-state cycling increased after training in LOW (from 26 ± 2 to 34 ± 2 µmol·kg−¹·min−¹, P < 0.01). Plasma free fatty acid oxidation was similar before and after training in both groups, but muscle-derived triacylglycerol oxidation increased after training in LOW (from 16 ± 1 to 23 ± 1 µmol·kg−¹·min−¹, P < 0.05). Training with low muscle glycogen also increased ß-hydroxyacyl-CoA-dehydrogenase protein content (P < 0.01). CONCLUSIONS: Training with low muscle glycogen reduced training intensity and, in performance, was no more effective than training with high muscle glycogen. However, fat oxidation was increased after training with low muscle glycogen, which may have been due to the enhanced metabolic adaptations in skeletal muscle.

Exercise training prevents hyperinsulinemia, muscular glycogen loss and muscle atrophy induced by dexamethasone treatment.

This study investigated whether exercise training could prevent the negative side effects of dexamethasone. Rats underwent a training period and were either submitted to a running protocol (60% physical capacity, 5 days/week for 8 weeks) or kept sedentary. After this training period, the animals underwent dexamethasone treatment (1 mg/kg per day, i.p., 10 days). Glycemia, insulinemia, muscular weight and muscular glycogen were measured from blood and skeletal muscle. Vascular endothelial growth factor (VEGF) protein was analyzed in skeletal muscles. Dexamethasone treatment evoked body weight loss (-24%), followed by muscular atrophy in the tibialis anterior (-25%) and the extensor digitorum longus (EDL, -15%). Dexamethasone also increased serum insulin levels by 5.7-fold and glucose levels by 2.5-fold compared to control. The exercise protocol prevented atrophy of the EDL and insulin resistance. Also, dexamethasone-treated rats showed decreased muscular glycogen (-41%), which was further attenuated by the exercise protocol. The VEGF protein expression decreased in the skeletal muscles of dexamethasone-treated rats and was unaltered by the exercise protocol. These data suggest that exercise attenuates hyperglycemia and may also prevent insulin resistance, muscular glycogen loss and muscular atrophy, thus suggesting that exercise may have some benefits during glucocorticoid treatment.

Embryonic neurons transplanted into the tibial nerve reinnervate muscle and reduce atrophy but NCAM expression persists.

OBJECTIVE: The aim of this study was to use the glycogen depletion technique to determine whether reinnervated muscle fibers could be distinguished from denervated muscle fibers by their size or by neural cell adhesion molecule (NCAM) expression. METHODS: Medial gastrocnemius muscles of five adult Fischer rats were reinnervated from embryonic neurons transplanted into the distal stump of the tibial nerve. Ten weeks later, the transplants were stimulated repeatedly to deplete reinnervated muscle fibers of glycogen. Areas of reinnervated (glycogen-depleted) muscle fibers were measured and assessed for NCAM expression. The areas of muscle fibers from reinnervated, denervated (n=5) and unoperated control muscles (n=5) were compared. RESULTS: Mean reinnervated muscle fiber area was significantly larger than the mean for denervated fibers (mean +/- SE: 40 +/- 6 and 10 +/- 1% of unoperated control fibers, respectively). NCAM was expressed in 55 +/- 7% of reinnervated fibers (mean +/- SE; range: 42-77%). The mean areas of reinnervated fibers that did or did not express NCAM were similar. NCAM was only expressed in some fibers in completely denervated muscles. DISCUSSION: Our data show that NCAM expression does not differentiate muscle denervation or reinnervation. Quantifying the area of large fibers did distinguish reinnervated muscle fibers from denervated fibers and showed that reinnervation of muscle from neurons placed in peripheral nerve is a strategy to rescue muscle from atrophy.

Contaminant concentrations and histopathological effects in Sacramento splittail (Pogonichthys macrolepidotus).

Sacramento splittail (Pogonichthys macrolepidotus) is a species of special concern in California, due to multiple anthropogenic stressors. To better understand the potential impact of contaminant exposure, adult splittail were captured from the Sacramento-San Joaquin River Delta (California, USA) and analyzed for histopathology and contaminant exposure. Organochlorine contaminants (PCBs, DDTs, dieldrin, chlordanes, and PBDEs) and trace metals (Ag, As, Cd, Co, Cr, Cu, Fe, Mn, Mo, Ni, Pb, Se, Sn, V, and Zn) were detected in the tissues of all fish. In many samples, human health screening values were exceeded for PCBs (83 of 90 samples), DDTs (32 samples), and dieldrin (37 samples). In contrast, thresholds for fish effects were rarely exceeded. Histopathological analysis indicated the presence of macrophage aggregates in gonads, kidneys, and liver and a high incidence of liver abnormalities. In the liver, observed effects were often moderate to severe for glycogen depletion (55 of 95 fish), lipidosis (hepatocellular vacuolation; 51 fish), and cytoplasmic inclusion bodies (33 fish). Correlations between histopathology and tissue contaminant concentrations were weak and inconsistent. Significant correlations were observed between histopathology indicators and reductions in fish size, body condition, lipid content, and liver weight. These results suggest that splittail histopathology varies as a function of health and nutritional status, rather than exposure to legacy organic and metal pollutants.

An extension to the compartmental model of type 1 diabetic patients to reproduce exercise periods with glycogen depletion and replenishment.

The purpose of this work is to present the main interactions promoted by exercise and synthesize them into mathematical equations. It is intended to extend the ability of the compartmental glucose-insulin model introduced by Sorensen [1985. A physiologic model of glucose metabolism in man and its use to design and assess improved insulin therapies for diabetes. Ph.D. Dissertation, Chemical Engineering Department, MIT, Cambridge] to reproduce variations in the blood glucose concentration induced by exercise in diabetic patients and to complement the previous work by Lenart and Parker [2002. Modeling exercise effects in type I diabetic patients. In: Proceedings of the 15th Triennial World Congress, Barcelona, Spain] and Lenart, DiMascio and Parker [2002. Modeling glycogen-exercise interactions in type I diabetic patients. In: Proceedings of the A.I.Ch.E. Annual Meeting, Indianapolis, IN]. The immediate consequences of exercise are incorporated in this research: redistribution of blood flows, increments in peripheral glucose and insulin uptakes, and increment in hepatic glucose production. The extended model was verified with experimental data for light and moderate intensity exercise. In addition, data extrapolation was introduced to simulate heavy intensity exercise. The hepatic glycogen reservoir limits the peripheral glucose uptake for prolonged exercise. Therefore, the depletion and replenishment of hepatic glycogen were modeled, looking to reproduce the blood glucose levels for a type 1 diabetic patient during a normal day, with meal intakes, insulin infusions and/or boluses, and a predefined exercise regime. From the extensive simulation evaluation, it is found that the new exercise model provides a good approximation to the available experimental data from literature.

False negative histochemical reaction for myophosphorylase activity in fulminant sepsis due to methicillin resistant Staphylococcus aureus.

We report a false negative histochemical reaction for myophosphorylase in the case of an 11 year old with fulminant Staphylococcus aureus. Due to increased creatine kinase levels and marked myoglobinuria a muscle biopsy was performed prior to death. The biopsy revealed rhabdomyolysis, glycogen depletion and absent myophosphorylase reactivity. Subsequent myophosphorylase quantification was normal. This unique case of a false negative myophosphorylase histochemical reaction is apparently related to sepsis.

Sex differences in energy metabolism and performance of teleost cardiac tissue.

This study examined the effects of different oxygenation levels and substrate availability on cardiac performance, metabolism, and biochemistry in sexually immature male and female rainbow trout (Oncorhynchus mykiss). Ventricle strips were electrically paced (0.5 Hz, 14 degrees C) in hyperoxic or hypoxic Ringer solution. Our results demonstrate that 1) males sustain isometric force production (F) longer than females under hyperoxia (P O2 = 640 mmHg) with exogenous glucose present; 2) contractility is not maintained under moderate (P O2 = 130 mmHg) or severe hypoxia (P O2 = 10-20 mmHg) with glucose in either sex; however, following reoxygenation, F is higher in females compared with males; and 3) female tissue has higher lactate levels, net lactate efflux, and lactate dehydrogenase activity than males, whereas males have higher glycogen, citrate synthase, and beta-hydroxy acyl-CoA dehydrogenase activities, and greater inotropic responses to exogenous glucose and octanoate. No sex differences were detected in responsiveness to epinephrine and inhibitors of glucose transport or activities of hexokinase and pyruvate kinase. We conclude that sex differences exist in rainbow trout cardiac tissue: females appear to prefer glycolysis for ATP production, whereas males have a higher capacity for aerobic and lipid metabolism.