Low Glycogen Research Articles

Medroxyprogesterone acetate alters the vaginal microbiota and microenvironment in women and increases susceptibility to HIV-1 in humanized mice.

ABSTRACTThe hormonal contraceptive medroxyprogesterone acetate (MPA) is associated with increased risk of human immunodeficiency virus (HIV), via incompletely understood mechanisms. Increased diversity in the vaginal microbiota modulates genital inflammation and is associated with increased HIV-1 acquisition. However, the effect of MPA on diversity of the vaginal microbiota is relatively unknown. In a cohort of female Kenyan sex workers, negative for sexually transmitted infections (STIs), with Nugent scores <7 (N=58 of 370 screened), MPA correlated with significantly increased diversity of the vaginal microbiota as assessed by 16S rRNA gene sequencing. MPA was also significantly associated with decreased levels of estrogen in the plasma, and low vaginal glycogen and α-amylase, factors implicated in vaginal colonization by lactobacilli, bacteria that are believed to protect against STIs. In a humanized mouse model, MPA treatment was associated with low serum estrogen, low glycogen and enhanced HIV-1 susceptibility. The mechanism by which the MPA-mediated changes in the vaginal microbiota may contribute to HIV-1 susceptibility in humans appears to be independent of inflammatory cytokines and/or activated T cells. Altogether, these results suggest MPA-induced hypo-estrogenism may alter key metabolic components that are necessary for vaginal colonization by certain bacterial species including lactobacilli, and allow for greater bacterial diversity in the vaginal microbiota.This article has an associated First Person interview with the first author of the paper.

Glucose and glycogen levels in piglets that differ in birth weight and vitality

In the pig, intrauterine crowding can greatly affect postnatal characteristics, among which birth weight and locomotion. In a previous study, we discovered that piglets with a low birth weight/low vitality (L piglets) have a reduced motor performance compared to piglets with a normal birth weight/normal vitality (N piglets). A possible explanation is that L piglets lack the energy to increase their motor performance to the level of that of N piglets. Blood glucose levels (GLU) and glycogen concentrations in skeletal muscle of the front (GLYFRONT) and hind leg (GLYHIND) and the liver (GLYLIVER) at birth and during the first 96 h postpartum were compared between L and N piglets. GLU at birth was the same for both groups. After birth, GLU immediately increased in N piglets, whereas it only increased after 8 h in L piglets. L piglets showed a lower GLYHIND at birth and did not use this glycogen during the first 8 h postpartum, while N piglets showed a gradual depletion. GLYLIVER at birth was 50% lower for L piglets and was unused during the studied period while N piglets consumed half of their GLYLIVER during the first 8 h. Based on these results, it is possible that lower glycogen concentrations at birth, the delayed increase in GLU and the lower use of glycogen during the first 8 h after birth negatively affect motor performance in L piglets. However, based on this study, it is unclear whether the low mobilization of glycogen by L piglets is a consequence, rather than a cause of their lower motor performance.

Glucose Injections at Birth, Warmth and Placing at a Nurse Sow Improve the Growth of IUGR Piglets.

Simple SummarySelection for hyperprolific sows has increased litter sizes and increased the number of small piglets per litter that require more management. Some of these small piglets have been exposed to intrauterine growth restriction, making them even more susceptible to a lower vitality and a higher mortality during the first few days. Administering an energy bolus at birth—such as glucose together with exposure to extra warmth—could be one way of increasing the growth and vitality of small, less viable piglets, ensuring piglet gain and survival. In addition, the results are relevant when in a relatively non-competitive environment—for example, placing them at a nurse sow suitable for rearing small piglets.Intrauterine growth-restricted piglets (IUGR) have a lower rectal temperature, whole-blood glucose, and lower glycogen storages at birth than normal piglets, giving them less energy to maintain body temperature and compete at the udder. The present paper investigated the effects of giving an energy supplementation three times after birth on rectal temperature, glucose levels, and growth until weaning in an on-farm trial. Eighty-eight newborn piglets were classified as IUGR (based on head morphology), placed under a heating lamp for one hour and allocated to one of four treatments—warmed water (WATER), glucose injection (GLUC), colostrum bolus (COLOS; porcine colostrum), and colostrum bolus and glucose injection (GLUC + COLOS)—before being placed at a nursing sow. Weight differences were found at day 21, with GLUC and GLUC + COLOS groups being the heaviest. Piglets in GLUC + COLOS had higher glucose levels at t = 3, 6, and 9 h compared to the other treatments (p = 0.027), but from t = 24 h and onwards, no difference was observed. For rectal temperature, no differences were observed. Collectively, these findings suggest that glucose injections at birth (i.e., as an energy source), one hour’s exposure to warmth and the placement of piglets with a nurse sow to reduce competition, enhance the growth of IUGR piglets.

The metabolic characteristics of susceptibility to wooden breast disease in chickens with high feed efficiency

This study was conducted to characterize metabolic differences between high feed efficiency (HFE) and low feed efficiency (LFE) chickens to investigate why feed efficient chickens are more susceptible to muscle abnormalities such as wooden breast disease. Gene expression profiles were generated by RNA sequencing of pectoralis major muscle samples from 10 HFE and 13 LFE broiler chickens selected from a modern broiler population. Metabolism-associated differentially expressed genes were identified and interpreted by Ingenuity Pathway Analysis and literature mining. Our RNA-seq data indicate decreased glycolytic capacity, increased fatty acid uptake, mitochondrial oxidation of fatty acids, and several other metabolic alterations in the pectoralis major muscle of HFE chickens. We also quantified glycogen content of the pectoralis major muscle and found that the HFE chickens had a significantly (P ≤ 0.05) lower glycogen content. Collectively, this study indicates extensive metabolic differences in the pectoralis major muscle between HFE and LFE chickens and helps identify metabolic features of susceptibility to muscle disorders in modern broiler chickens.

Muscle Glycogen Content during Endurance Training under Low Energy Availability

The present study investigated the effects of three consecutive days of endurance training under conditions of low energy availability (LEA) on the muscle glycogen content, muscle damage markers, endocrine regulation, and endurance capacity in male runners. Seven male long-distance runners (19.9 ± 1.1 yr, 175.6 ± 4.7 cm, 61.4 ± 5.3 kg, maximal oxygen uptake [V˙O2max]: 67.5 ± 4.3 mL·kg·min) completed two trials consisting of three consecutive days of endurance training under LEA (18.9 ± 1.9 kcal·kg FFM·d) or normal energy availability (NEA) (52.9 ± 5.0 kcal·kg FFM·d). The order of the two trials was randomized, with a 2-wk interval between trials. The endurance training consisted of 75 min of treadmill running at 70% of V˙O2max. Muscle glycogen content, respiratory gas variables, and blood and urine variables were measured in the morning for three consecutive days of training (days 1-3) and on the following morning after training (day 4). As an indication of endurance capacity, time to exhaustion at 19.0 ± 0.8 km·h to elicit 90% of V˙O2max was evaluated on day 4. During the training period, body weight, fat-free mass, and skeletal muscle volume were significantly reduced in LEA (P = 0.02 for body weight and skeletal muscle volume, P = 0.01 for fat-free mass). Additionally, muscle glycogen content was significantly reduced in LEA (~30%, P < 0.001), with significantly lower values than those in NEA (P < 0.001). Time to exhaustion was not significantly different between the two trials (~20 min, P = 0.39). Three consecutive days of endurance training under LEA decreased muscle glycogen content with lowered body weight. However, endurance capacity was not significantly impaired.

Twice-a-day training improves mitochondrial efficiency, but not mitochondrial biogenesis, compared with once-daily training

Exercise training performed with lowered muscle glycogen stores can amplify adaptations related to oxidative metabolism, but it is not known if this is affected by the "train-low" strategy used (i.e., once-daily versus twice-a-day training). Fifteen healthy men performed 3 wk of an endurance exercise (100-min) followed by a high-intensity interval exercise 2 (twice-a-day group, n = 8) or 14 h (once-daily group, n = 7) later; therefore, the second training session always started with low muscle glycogen in both groups. Mitochondrial efficiency (state 4 respiration) was improved only for the twice-a-day group (group × training interaction, P < 0.05). However, muscle citrate synthase activity, mitochondria, and lipid area in intermyofibrillar and subsarcolemmal regions, and PGC1α, PPARα, and electron transport chain relative protein abundance were not altered with training in either group (P > 0.05). Markers of aerobic fitness (e.g., peak oxygen uptake) were increased, and plasma lactate, O2 cost, and rating of perceived exertion during a 100-min exercise task were reduced in both groups, although the reduction in rating of perceived exertion was larger in the twice-a-day group (group × time × training interaction, P < 0.05). These findings suggest similar training adaptations with both training low approaches; however, improvements in mitochondrial efficiency and perceived effort seem to be more pronounced with twice-a-day training.NEW & NOTEWORTHY We assessed, for the first time, the differences between two "train-low" strategies (once-daily and twice-a-day) in terms of training-induced molecular, functional, and morphological adaptations. We found that both strategies had similar molecular and morphological adaptations; however, only the twice-a-day strategy increased mitochondrial efficiency and had a superior reduction in the rating of perceived exertion during a constant-load exercise compared with once-daily training. Our findings provide novel insights into skeletal muscle adaptations using the "train-low" strategy.

Biometry, shell resistance and attachment of zebra and quagga mussels at the beginning of their co-existence in large European lakes

In invasive dreissenid communities, the zebra mussel usually appears earlier and then is displaced by the quagga mussel. We analysed length-weight allometric relationships, attachment strength (2 days, 1 week and 1 month of exposure), shell crushing resistance and glycogen content across the entire size range of both species in large shallow European lakes where this displacement has recently occurred. In Lake Balaton (Hungary) and Ijsselmeer (The Netherlands), the soft tissue dry weight increment of zebra mussels per unit length decreased after the quagga mussel invasion and became lower than that of quagga mussels. In Lake Markermeer (the Netherlands), having relatively worse environmental conditions, dry weight increment per unit length was always higher in quagga mussels than in zebra mussels, but no negative change in dry weight increment occurred in zebra mussels during the quagga mussel invasion. Small zebra mussels had more resistant shells and stronger attachment than quagga mussels. These differences were reduced (shell hardness) or reversed (long-term attachment) in larger individuals. Zebra mussels had lower glycogen content than quagga mussels across the entire size range. Thus, the quagga mussel advantage over zebra mussel likely consists in the faster dry weight increment per unit length and higher storage product contents of the former, due to its lower investments in attachment strength and shell crushing resistance.

Transcriptional Regulation Of Substrate Metabolism Following Carbohydrate Ingestion During Exercise Initiated With Different Glycogen Concentrations

BACKGROUND: Starting aerobic exercise with low muscle glycogen content elicits greater fat and less carbohydrate utilization than exercise started with high muscle glycogen content, even when exogenous carbohydrate is ingested during exercise. The mechanisms contributing to greater fat utilization despite ingesting carbohydrate during exercise initiated with low glycogen are not delineated. PURPOSE: Characterize transcriptional regulation of substrate metabolism in response to carbohydrate ingestion during steady-state exercise initiated with low muscle glycogen. METHODS: In a randomized, crossover design, 12 men (mean ± SD, age, 21 ± 4 y; body mass, 83 ± 11 kg; VO2peak, 44 ± 3 mL/kg/min) completed two cycle ergometry glycogen depletion trials, followed by a 24 h period of either high fat (1.5 g/kg carbohydrate, 3.0 g/kg fat) or high carbohydrate (6.0 g/kg carbohydrate, 1.0 g/kg fat) isocaloric refeeding to elicit low (LOW) or adequate (AD) glycogen content the following morning before initiating 80-min of cycle ergometry (64 ± 3% VO2peak) while ingesting 146 g of carbohydrate. Transcriptional regulation of substrate metabolism was assessed using RT-qPCR in vastus lateralis biopsy samples obtained before (PRE) and after (POST) the 80-min exercise bout. RESULTS: PRE glycogen synthase kinase 3α expression was 40% lower (P<0.05; time-by-treatment interaction) in LOW than AD. GLUT4, hexokinase 2, phosphofructokinase, and pyruvate kinase expression were not different between LOW and AD. PRE fatty acid translocase was 40% higher (P<0.05; time-by-treatment interaction) in LOW than AD. Independent of time, fatty acid binding protein, carnitine palmitoyltransferase 1A, and hydroxyacyl-CoA dehydrogenase/3-ketoacyl-CoA expression were each ~40% higher (P<0.05; time effect) in LOW than AD. In LOW, POST peroxisome proliferator-activated receptor δ was 177% higher (P<0.05 time-by-treatment interaction) than PRE, with no change in AD. CONCLUSION: Initiating aerobic exercise with low muscle glycogen content upregulates the transcriptional control of fat oxidation without modulating intramuscular regulation of glucose metabolism, even when exogenous glucose is ingested during exercise.

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 β‐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.

The Hypoglycemic Effects of Ginger and Garlic Administration on Induced Diabetic Rats

This work was designed to investigate the possible hypoglycemic effects of ginger (Zingiber officinal) and garlic (Allium sativum) administration on type 2 diabetesinduced in rats. Seventy male adult albino rats were randomly divided into seven groups of ten animals: Normal Control (Cnt), Diabetic Control (CntD), Ginger Low (GNL), Ginger High (GNH), Garlic Low (GRL), Garlic High (GRH) and a combination group (GNH+GRH). Diabetes was induced by an intraperitoneal injection of streptozotocin (STZ, 65 mg/kg of body weight) in all groups except the Cnt group. Rats were treated with ginger and garlic powders in different doses for 2 months. At the end of experiment, glycated hemoglobin (HbA1c), serum glucose, serum insulin, cholesterol, and high density lipoprotein (HDL)concentrations, low density lipoprotein (LDL), liver glycogen and glucagon levels were estimated.Expression of Glucose-6-Phosphatase and Glucokinase genes in liver samples from each group were normalized with housekeeping gene (s-actin) using reverse transcriptase real time Polymerase chain reaction. Serum insulin and HDL concentrations were significantly (P< 0.05) higherbutbody weight, fasting blood glucose, total cholesterol, LDLand HbA1clevels were significantly (P< 0.05) lower in the Cnt, GNH, GRH and GNH+GRHgroups compared to the CntD, GNL and GRL groups. Liver glycogen level was significantly (P< 0.05) higher and serum glucagon level was significantly (P< 0.05) lower in the combination group only but non significant difference was observed for the other groups. The expression of liver Glucose-6-Phosphatase gene was significantly (P< 0.05) downregulated but the Glucokinase gene was significantly (P< 0.05) upregulated in STZ diabetic rats treated withhigh doses of ginger and garlic powders. This study suggests that ginger and garlic powders can be used to ameliorate type 2 diabetes and might also help in preventing secondary diabetic complications.

Muscle Energy and Salivary Cytokine Response During a 100 Mile Trail Run: A Case Study

PURPOSE: The purpose of this study was to determine the impact of competing in a 100-mile ultramarathon on muscle fuel stores and cytokine production. METHODS: One experienced male runner (40 yrs, 76.3 kg, 177.8 cm) completed the 100.5-mile distance in 32.9 hrs. Measurements were collected pre-race, at each support crew accessible aid station (28.5, 41, 52, 66, and 80 miles), and post-race. Measures included saliva cytokine markers (IL-6 and TNF-α), muscle energy status, and body mass. Saliva was collected using a passive drool technique and samples were stored on dry ice until they could be sent out for analysis. Muscle energy status (MES) was determined by scanning the right rectus femoris with a portable ultrasound transducer. Scanned muscle images were uploaded to a cloud-based application where they were analyzed for MES, which is an arbitrary number assigned to the muscle based on predicted glycogen concentration. Caloric expenditure was predicted based off average pace and terrain. Caloric intake was monitored by a combination of self-reporting, product wrapper collection, and unconsumed fluid measurement. RESULTS: Caloric expenditure was estimated at 13,184 kcal (401 kcal/hr), while caloric intake was recorded at 5888.3 kcal (180 kcal/hr). Body mass declined 2.4% from pre to post-race, although it fluctuated throughout the race (76.3, 74.7, 74.1, 75.1, 75.9, 75.4, 74.5 kg; respectively). MES was reduced 57% from pre to post-race, but also fluctuated throughout the race (88.0, 34.4, 71.9, 25.1, 69.1, 70.9, 38.2). IL-6 levels correlated with MES values (R2= 0.6987). TNF-α values followed a similar pattern to IL-6; however, no correlation was found between TNF-α and MES. CONCLUSION: These data provide some interesting insights into potential MES plasticity and cytokine regulation during prolonged exercise. More specifically, fluctuating MES values observed during the current activity suggest that glycogenolysis and glycogenesis may occur throughout an ultra-event depending on terrain and intensity, even with a discrepancy between caloric intake and expenditure. Additionally, salivary IL-6 activity may be related to MES, suggesting that periods of low glycogen may increase physiological stress.

Exercising with low muscle glycogen content increases fat oxidation and decreases endogenous, but not exogenous carbohydrate oxidation

BackgroundInitiating aerobic exercise with low muscle glycogen content promotes greater fat and less endogenous carbohydrate oxidation during exercise. However, the extent exogenous carbohydrate oxidation increases when exercise is initiated with low muscle glycogen is unclear. PurposeDetermine the effects of muscle glycogen content at the onset of exercise on whole-body and muscle substrate metabolism. MethodsUsing a randomized, crossover design, 12 men (mean ± SD, age: 21 ± 4 y; body mass: 83 ± 11 kg; VO2peak: 44 ± 3 mL/kg/min) completed 2 cycle ergometry glycogen depletion trials separated by 7-d, followed by a 24-h refeeding 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 stores. Participants then performed 80 min of steady-state cycle ergometry (64 ± 3% VO2peak) while consuming a carbohydrate drink (95 g glucose +51 g fructose; 1.8 g/min). Substrate oxidation (g/min) was determined by indirect calorimetry and 13C. Muscle glycogen (mmol/kg dry weight), pyruvate dehydrogenase (PDH) activity, and gene expression were assessed in muscle. ResultsInitiating steady-state exercise with LOW (217 ± 103) or AD (396 ± 70; P < 0.05) muscle glycogen did not alter exogenous carbohydrate oxidation (LOW: 0.84 ± 0.14, AD: 0.87 ± 0.16; P > 0.05) during exercise. Endogenous carbohydrate oxidation was lower and fat oxidation was higher in LOW (0.75 ± 0.29 and 0.55 ± 0.10) than AD (1.17 ± 0.29 and 0.38 ± 0.13; all P < 0.05). Before and after exercise PDH activity was lower (P < 0.05) and transcriptional regulation of fat metabolism (FAT, FABP, CPT1a, HADHA) was higher (P < 0.05) in LOW than AD. ConclusionInitiating exercise with low muscle glycogen does not impair exogenous carbohydrate oxidative capacity, rather, to compensate for lower endogenous carbohydrate oxidation acute adaptations lead to increased whole-body and skeletal muscle fat oxidation.

Low-Carbohydrate Training Increases Protein Requirements of Endurance Athletes.

Training with low-carbohydrate (CHO) availability enhances markers of aerobic adaptation and has become popular to periodize throughout an endurance-training program. However, exercise-induced amino acid oxidation is increased with low muscle glycogen, which may limit substrate availability for postexercise protein synthesis. We aimed to determine the impact of training with low-CHO availability on estimates of dietary protein requirements. Eight endurance-trained males (27 ± 4 yr, 75 ± 10 kg, 67 ± 10 mL·kg body mass·min) completed two trials matched for energy and macronutrient composition but with differing CHO periodization. In the low-CHO availability trial (LOW), participants consumed 7.8 g CHO·kg before evening high-intensity interval training (10 × 5 min at 10-km race pace, 1 min rest) and subsequently withheld CHO postexercise (0.2 g·kg). In the high-CHO availability trial (HIGH), participants consumed 3 g CHO·kg during the day before high-intensity interval training, and consumed 5 g CHO·kg that evening to promote muscle glycogen resynthesis. A 10-km run (~80% HRmax) was performed the following morning, fasted (LOW) or 1 h after consuming 1.2 g CHO·kg (HIGH). Whole-body phenylalanine flux and oxidation were determined over 8 h of recovery via oral [C]phenylalanine ingestion, according to standard indicator amino acid oxidation methodology, while consuming sufficient energy, 7.8 g CHO·kg·d, and suboptimal protein (0.93 g·kg·d). Fat oxidation (indirect calorimetry) during the 10-km run was higher in LOW compared with HIGH (0.99 ± 0.35 g·min vs 0.60 ± 0.26 g·min, P < 0.05). phenylalanine flux during recovery was not different between trials (P > 0.05) whereas phenylalanine oxidation (reciprocal of protein synthesis) was higher in LOW compared with HIGH (8.8 ± 2.7 μmol·kg·h vs 7.9 ± 2.4 μmol·kg·h, P < 0.05), suggesting a greater amino acid requirement to support rates of whole-body protein synthesis. Our findings suggest that performing endurance exercise with low-CHO availability increases protein requirements of endurance athletes.

SUN-024 Uncovering a Novel Role for Nuclear Receptor Fxr and Shp in Regulating N-Linked Glycosylation

Nuclear receptor Farnesoid X Receptor (Fxr) and Small Heterodimer Partner (Shp) are key regulators of glucose, fat and bile acid homeostasis. As expected, liver-specific deletion of both Fxr and Shp (LDKO) sensitizes mice to bile acid excess. Surprisingly, high throughput RNA-sequencing analysis revealed increases in key glycosyltransferases involved in “decorating” various glycoproteins in LDKO livers. Remarkably, we were able to confirm increased glycan decoration and branching in LDKO livers using glycomics and glycoproteomics approaches. Further, electron microscopic analysis revealed disruption and dilation of Golgi network, which is consistent with aberrant glycosylation. LDKO mice were hypoglycemic, stored lower glycogen, indicating glucose being utilized to meet the increased glycosylation demand. Taken together, we uncover a novel role for hepatic Fxr-Shp axis in maintaining the glycosylation status of proteins in the liver.

Myocardial glycogen depletion leads to improved left ventricular remodeling in a mouse MI model

High glycogen (GLN) content is generally considered deleterious in prolonged ischemia, however, the exact role of GLN during permanent myocardial infarction (MI) and left ventricular (LV) remodeling post-MI, remains poorly understood. This study aimed to investigate whether myocardial GLN depletion can attenuate adverse LV remodeling post-MI. We used a transgenic knock-in (KI) mouse, in which the allosteric pathway of GLN synthesis is inhibited in muscle, leading to dramatically suppressed myocardial GLN levels. WT and KI male mice (10–12 weeks old) were subjected to MI by left anterior descending (LAD) coronary artery permanent ligation. Heart function was measured by 2D-echo (Vevo 2100, Visualsonics). Mice were sacrificed 56 days post-MI and hearts were collected to measure myocardial GLN content and perform IHC and mRNA studies. Basal GLN content was dramatically depressed in KI hearts. We demonstrated a robustly reduced LV dilatation in KI mice 56 days post-MI, as evidenced by lower end-diastolic volume (WT: 167.69 ± 13.42 vs KI: 138.00 ± 4.62 μl; P < 0.05) and end-systolic volume (WT: 147.62 ± 14.58 vs KI: 123.15 ± 4.05 μl; P < 0.05). Moreover, KI mice exhibited attenuated global LV fibrosis (WT: 61.69 ± 11.10 vs KI: 37.42 ± 6.90%; P < 0.05) and a significant decrease in border zone fibrosis (WT: 58.59 ± 12.11 vs KI: 30.33 ± 4.94%; P < 0.05). Surprisingly, KI MI mice demonstrated a dramatic decrease in myocardial rupture incidence (WT: 40.00 vs KI: 6.25%) and improved survival 56 days post-MI (WT: 42.86% vs KI: 60%). GLN depletion in KI hearts attenuates post-MI adverse LV remodeling and improves survival compared to WT. There is a strong correlation between the reduction of cardiac remodeling and a drastic effect on fibrosis deposition, especially in the border zone. Further studies are required, in order to shed light onto the association between low GLN content, cardioprotection and fibrosis.

Methodological considerations for studies of brain glycogen.

Glycogen stores in the brain have been recognized for decades, but the underlying physiological function of this energy reserve remains elusive. This uncertainty stems in part from several technical challenges inherent in the study of brain glycogen metabolism. These include low glycogen content in the brain, non-homogeneous labeling of glycogen by radiotracers, rapid glycogenolysis during postmortem tissue handling, and effects of the stress response on brain glycogen turnover. Here we briefly review the aspects of the glycogen structure and metabolism that bear on these technical challenges and present ways they can be addressed.

The Role of Serum Alpha-Amylase and Glycogen Synthase in the Anti-Diabetic Potential of Terminalia catappa Aqueous Leaf Extract in Diabetic Wistar Rats

Background: The endocrinal abnormalities in diabetes mellitus as one of the numerous metabolic disorders is associated with derangement in exocrine functions of the pancreas and ultimately influences blood glucose regulation.&#x0D; Aim: The study was aimed at assessing the role of alpha-amylase and glycogen synthase in anti-diabetic potential of Terminalia catappa in diabetic rats. &#x0D; Materials and Methods: Thirty five (35) Wistar rats were assigned to 5 groups of 7 animals each. Group 1 served as the control administered distilled water at 5ml/kg bodyweight and group 2 was a non diabetic group given orally, 130/kg body weight of aqueous leaf extract of Terminalia catappa. Groups 3, 4 and 5 received a single dose of 150mg/kg body weight of alloxan solution intraperitoneally to induce diabetes and rats with blood glucose levels ≥200mg/dl after 72 hours were considered diabetic. This was followed by oral administration of 5ml/kg bodyweight of distilled water, 130mg/kg body weight of Terminalia catappa leaf extract orally and subcutaneous administration of insulin, 0.75U/kg body weight to groups 3 (diabetic), 4(diabetic + extract) and 5 (diabetic + insulin) respectively.&#x0D; Results: The results showed significant (P&lt;.05) increase in serum level of alpha-amylase and glycogen synthase in both non-diabetic extract treated and diabetic groups when compared to control. But these enzymes significantly (P&lt;.05) reduced in diabetic extract and insulin treated groups when compared to the diabetic group. &#x0D; Conclusion: Therefore the hypoglycaemic potential of Terminalia catappa leaf extract could be attributed to its ability to reduce alpha-amylase level while lowered glycogen synthase might be secondary to reduction in blood glucose.

Association and Functional Analyses Revealed That PPP1R3B Plays an Important Role in the Regulation of Glycogen Content in the Pacific Oyster Crassostrea gigas.

The Pacific oyster (Crassostrea gigas) is one of the most important aquaculture species worldwide. Glycogen contributes greatly to the special taste and creamy white color of oysters. Previous genome-wide association studies (GWAS) identified several single nucleotide polymorphism (SNP) sites that were strongly related to glycogen content. Genes within 100 kb upstream and downstream of the associated SNPs were screened. One gene annotated as protein phosphatase 1 regulatory subunit 3B (PPP1R3B), which can promote glycogen synthesis together with protein phosphatase 1 catalytic subunit (PPP1C) in mammals, was selected as a candidate gene in this study. First, full-length CgPPP1R3B was cloned and its function was characterized. The gene expression profiles of CgPPP1R3B in different tissues and seasons showed a close relationship to glycogen content. RNA interference (RNAi) experiments of this gene in vivo showed that decreased CgPPP1R3B levels resulted in lower glycogen contents in the experimental group than in the control group. Co-immunoprecipitation (Co-IP) and yeast two-hybrid (Y2H) assays indicated that CgPPP1R3B can interact with CgPPP1C, glycogen synthase (CgGS) and glycogen phosphorylase (CgGP), thus participating in glycogen metabolism. Co-sedimentation analysis in vitro demonstrated that the CgPPP1R3B protein can bind to glycogen molecules directly, and these results indicated the conserved function of the CgPPP1R3B protein compared to that of mammals. In addition, thirteen SNPs were precisely mapped in this gene. Ten of the thirteen SNPs were confirmed to be significantly (p < 0.05) related to glycogen content in an independent wild population (n = 288). The CgPPP1R3B levels in oysters with high glycogen content were significantly higher than those of oysters with low glycogen content, and gene expression levels were significantly associated with various genotypes of four associated SNPs (p < 0.05). The data indicated that the associated SNPs may control glycogen content by regulating CgPPP1R3B expression. These results suggest that CgPPP1R3B is an important gene for glycogen metabolic regulation and that the associated SNPs of this gene are potential markers for oyster molecular breeding for increased glycogen content.

Hepatic effects of long-term tamoxifen administration to cycling female rats.

The metabolic implications of tamoxifen (TAM) used as preventive therapy of young premenopausal women with high risk of breast cancer is unknown. To unravel this problem, an animal model of long-term TAM administration to cycling young adult female rats was used to evaluate its effects in the liver. Body weight and food consumption were monitored, and at the end of the study, both parameters were lower in TAM-treated rats. Biochemical measurements showed that the TAM administration induced alterations in serum levels of liver enzymes when compared with control rats at different stages of the estrous cycle. In TAM-treated rats, lower glycogen storage was observed in hepatocytes close to the portal areas and pericentrolobular cells had a higher concentration of glycogen. Liver sections of TAM-treated rats presented mild steatosis-a high percentage of area occupied by lipid droplets in the hepatocytes. These results point to metabolic changes upon long-term TAM therapy.

Comparison of del Nido and histidine-tryptophan-ketoglutarate cardioplegia solutions in pediatric patients undergoing open heart surgery: A prospective randomized clinical trial

ObjectivesWe conducted a prospective randomized controlled trial to compare del Nido (DN) and histidine-tryptophan-ketoglutarate (HTK) cardioplegia solution in pediatric patients undergoing intracardiac tetralogy of Fallot repair. MethodsOne hundred consecutive patients 12 years of age or younger, undergoing intracardiac repair of tetralogy of Fallot were randomized into DN (n = 50) and HTK (n = 50) groups. Cardioplegia strategy consisted of a single dose of DN (20 mL/kg) or HTK (6 mL/kg/min for 6 minutes). Primary outcome was cardiac index (CI). Secondary outcomes were ventricular arrhythmias post cross-clamp release, time to peripheral rewarming, duration of mechanical ventilation, inotropic score, intensive care unit and hospital stay, and serum levels of troponin-I, interleukin-6, and tumor necrosis factor-α. Ultrastructural changes in the myocardium were assessed. ResultsCI was significantly higher in the DN group compared with the HTK group at 6 (P = .005) and 24 hours (P < .001) after surgery. It was on an average 0.44 L/min/m2 higher in the DN group at any time point (P = .004). Time for complete cessation of electrical activity was longer in the HTK group (P = .01) and more patients in the HTK group had ventricular arrhythmias post cross-clamp release (P = .03). Duration of mechanical ventilation (P = .006), intensive care unit stay (P = .05), and hospital stay (P < .001) were lower in the DN group. Patients in the DN group had lower troponin I levels 24 hours after cardiopulmonary bypass (P < .001). Electron microscopic studies showed more myocardial edema (P = .02) and myofibrillar disarray (P = .04) in the HTK group along with lower glycogen stores (P = .04). DN cardioplegia was more cost-effective than HTK cardioplegia (P < .001). ConclusionsDN cardioplegia was associated with better preservation of CI, less duration of mechanical ventilation, shorter intensive care unit and hospital stays, lower inotropic scores, and less release of troponin-I. Electron microscopy showed less myocardial edema and better preservation of the myofibrillar architecture and glycogen stores in the DN group.