Liver Glycogen Stores Research Articles

Polarity Protein AF6 Controls Hepatic Glucose Homeostasis and Insulin Sensitivity by Modulating IRS1/AKT Insulin Pathway in an SHP2-Dependent Manner.

Insulin resistance is a major contributing factor in the development of metabolic disease. Although numerous functions of the polarity protein AF6 (afadin and MLLT4) have been identified, a direct effect on insulin sensitivity has not been previously described. We show that AF6 is elevated in the liver tissues of dietary and genetic mouse models of diabetes. We generated liver-specific AF6 knockout mice and show that these animals exhibit enhanced insulin sensitivity and liver glycogen storage, whereas overexpression of AF6 in wild-type mice by adenovirus-expressing AF6 led to the opposite phenotype. Similar observations were obtained from in vitro studies. In addition, we discovered that AF6 directly regulates IRS1/AKT kinase-mediated insulin signaling through its interaction with Src homology 2 domain-containing phosphatase 2 (SHP2) and its regulation of SHP2's tyrosine phosphatase activity. Finally, we show that knockdown of hepatic AF6 ameliorates hyperglycemia and insulin resistance in high-fat diet-fed or db/db diabetic mice. These results demonstrate a novel function for hepatic AF6 in the regulation of insulin sensitivity, providing important insights about the metabolic role of AF6.

A new perspective of triptolide-associated hepatotoxicity: Liver hypersensitivity upon LPS stimulation

ObjectiveThis study was designed to investigate whether the mice treated with triptolide (TP) could disrupt the liver immune homeostasis, resulting in the inability of the liver to eliminate the harmful response induced by lipopolysaccharide (LPS). In addition, we explored whether apoptosis and necroptosis played a critical role in the progression of the hepatotoxicity induced by TP-LPS co-treatment. MethodsFemale C57BL/6 mice were continuously administrated with two different doses of TP (250 μg/kg and 500 μg/kg) intragastrically for 7 days. Subsequently, a single dose of LPS (0.1 mg/kg) was injected intraperitoneally to testify whether the liver possesses the normal immune function to detoxicate the exogenous pathogen’s stimulation. To prove the involvement of apoptosis and necroptosis in the liver damage induced by TP-LPS co-treatment, apoptosis inhibitor Z-VAD-FMK (FMK) and necroptosis inhibitor necrostatin (Nec-1) were applied before the stimulation of LPS to diminish the apoptosis and necroptosis respectively. ResultsTP or LPS alone did not induce significant liver damage. However, compared with TP or LPS treated mice, TP-LPS co-treatment mice showed obvious hepatotoxicity with a remarkable elevation of serum ALT and AST accompanied by abnormal bile acid metabolism, a depletion of liver glycogen storage, aberrant glucose metabolism, an up-regulation of inflammatory cell infiltration, and an increase of apoptosis and necroptosis. Intraperitoneal injection of FMK or Nec-1 could counteract the toxic reactions induced by TP-LPS co-treatment. ConclusionTP could disrupt the immune response, resulting in hypersensitivity of the liver upon LPS stimulation, ultimately leading to abnormal liver function and cell death. Additionally, apoptosis and necroptosis played a vital role in the development of liver damage induced by TP-LPS co-treatment.

Dietary sugars, exercise and hepatic carbohydrate metabolism.

The present paper reviews the physiological responses of human liver carbohydrate metabolism to physical activity and ingestion of dietary sugars. The liver represents a central link in human carbohydrate metabolism and a mechanistic crux point for the effects of dietary sugars on athletic performance and metabolic health. As a corollary, knowledge regarding physiological responses to sugar ingestion has potential application to either improve endurance performance in athletes, or target metabolic diseases in people who are overweight, obese and/or sedentary. For example, exercise increases whole-body glycogen utilisation, and the breakdown of liver glycogen to maintain blood glucose concentrations becomes increasingly important as exercise intensity increases. Accordingly, prolonged exercise at moderate-to-high exercise intensity results in depletion of liver glycogen stores unless carbohydrate is ingested during exercise. The exercise-induced glycogen deficit can increase insulin sensitivity and blood glucose control, and may result in less hepatic lipid synthesis. Therefore, the induction and maintenance of a glycogen deficit with exercise could be a specific target to improve metabolic health and could be achieved by carbohydrate (sugar) restriction before, during and/or after exercise. Conversely, for athletes, maintaining and restoring these glycogen stores is a priority when competing in events requiring repeated exertion with limited recovery. With this in mind, evidence consistently demonstrates that fructose-containing sugars accelerate post-exercise liver glycogen repletion and could reduce recovery time by as much as half that seen with ingestion of glucose (polymers)-only. Therefore, athletes aiming for rapid recovery in multi-stage events should consider ingesting fructose-containing sugars to accelerate recovery.

PO-255 Optimization of Ultrasonic Extraction of Maca Polysaccharides and Evaluation of its Anti-fatigue Ability

Objective The aim of this study was to establish the optimal extraction conditions of polysaccharides of Maca (Lepidium meyenii Walp) and explore its anti-fatigue ability of exhaustive exercise rats.
 Methods Response surface methodology, based on Box-Behnken design, was used to optimize of ultrasonic extraction conditions of maca polysaccharides.Three independent variables (ratio of water to raw material, ultrasonic time, ultrasonic temperature) were taken into consideration. Subsequently, 80 male SD rats were randomly divided into 4 groups, negative control group, low dose group (ML, 130mg/Kg.bw/d), middle dose group (MM, 270mg/Kg.bw/d), high dose group (MH, 800mg/Kg.bw/d). After continuous oral gavage for 30 days, 10 rats were randomly selected from each group to measure the liver glycogen, and the remaining 40 were used to determine the exhaustion swimming time, biochemical indicators of exercise capacity in rats.
 Results 1. The best extracting method the ratio of material to liquid 1:22g/ml, ultrasonic time was 28min, ultrasonic temperature was 59 degrees centigrade, the extraction rate was 17.6754%. 2. Both middle and high doses of maca polysaccharides could significantly improve the swimming time of exhausted rats. 3. The maca polysaccharides group (ML, MM, MH) could effectively inhibit the growth of lactic acid in rats and accelerated the elimination of lactic acid. The effect of high dose MH group was the most obvious(P＜0.05). 4. The content of BUN in swimming rats was reduced by different doses of maca polysaccharides. High dose of maca polysaccharides on reducing the content of MDA was the most significant(P＜0.05). 6. Different doses of maca polysaccharides increased liver glycogen storage in rats, the high dose of maca polysaccharides to improve the effect of liver glycogen content of rats was the most significantly(P＜0.05).
 Conclusions 1. The optimum extraction conditions of maca polysaccharides was as follows: the ratio of material to liquid was 1:22g/ml, the ultrasonic time was 30min, the ultrasonic temperature was 60, and the extraction rate was 17.6754%. 2. Maca polysaccharides could improve the antioxidant capacity of the body, improve energy reserves; prolonged exhaustive swimming time.

Etiology and clinical pattern of liver diseases in children

Background: liver diseases may not be recognized by clinicians, who can lead to a subsequent delayin the initiation of effective therapies, the commonest presenting signs and symptoms of pediatric liverdiseases include hepatomegaly, jaundice, coagulopathy or elevation of the liver enzymes or wasteproducts as ammonia.Objectives: To highlight the etiologies, pattern of presentations and the route of diagnosis of all liverdiseases in children less than 10 years referred to the Gastroenterology and Hepatology Unit inChildren Welfare Teaching Hospital over a six months period.Patients and methods: A prospective study was conducted in the Gastroenterology and HepatologyUnit in the Children Welfare Teaching Hospital / Baghdad Medical City hospital during the periodfrom first of December 2016 to the end of thirty first of May 2017.Forty patients aged below 10 years were thoroughly assessed for possible causes of liver disease andthe severity of liver damage. These patients were subjected to a detailed history, thorough physicalexamination and a list of investigationsResults: forty patients their age less than 10 years, the most common age group in this study was from1 year to 5 years was 17(40%), males are more affected than females in the ratio of 1.5:1, it was foundthat the mean age of onset is the biliary atresia and Galactosemia cases were within the first week oflife, congenital infection cases presented earlier than the two above groups. In this study most of thecases were diagnosed clinically and by available investigations and only cases of biliary atresia andglycogen storage diseases were diagnosed by liver biopsy.Conclusion: All patients presented late with complications, biliary atresia cases were very late inpresentation, all with fibrosis. Family history usually very important in hereditary liver diseases asgalactosemia and glycogen storage disease a careful physical examination in addition to previousmedical history most of the time gives a clue to the final diagnosis.

Etiology and clinical pattern of liver diseases in children

Background: liver diseases may not be recognized by clinicians, who can lead to a subsequent delayin the initiation of effective therapies, the commonest presenting signs and symptoms of pediatric liverdiseases include hepatomegaly, jaundice, coagulopathy or elevation of the liver enzymes or wasteproducts as ammonia.Objectives: To highlight the etiologies, pattern of presentations and the route of diagnosis of all liverdiseases in children less than 10 years referred to the Gastroenterology and Hepatology Unit inChildren Welfare Teaching Hospital over a six months period.Patients and methods: A prospective study was conducted in the Gastroenterology and HepatologyUnit in the Children Welfare Teaching Hospital / Baghdad Medical City hospital during the periodfrom first of December 2016 to the end of thirty first of May 2017.Forty patients aged below 10 years were thoroughly assessed for possible causes of liver disease andthe severity of liver damage. These patients were subjected to a detailed history, thorough physicalexamination and a list of investigationsResults: forty patients their age less than 10 years, the most common age group in this study was from1 year to 5 years was 17(40%), males are more affected than females in the ratio of 1.5:1, it was foundthat the mean age of onset is the biliary atresia and Galactosemia cases were within the first week oflife, congenital infection cases presented earlier than the two above groups. In this study most of thecases were diagnosed clinically and by available investigations and only cases of biliary atresia andglycogen storage diseases were diagnosed by liver biopsy.Conclusion: All patients presented late with complications, biliary atresia cases were very late inpresentation, all with fibrosis. Family history usually very important in hereditary liver diseases asgalactosemia and glycogen storage disease a careful physical examination in addition to previousmedical history most of the time gives a clue to the final diagnosis.

Nutritional recovery with a soybean diet impaired the glucagon response but did not alter liver gluconeogenesis in the adult offspring of rats deprived of protein during pregnancy and lactation

Nutritional recovery of early malnutrition with a soybean diet reduces liver glycogen stores in the fed state and produces liver insulin resistance. We investigated whether nutritional recovery on a soybean flour diet alters hepatic gluconeogenesis in the adult offspring of rats deprived of protein during pregnancy and lactation. Male rats from mothers that were fed either 17% (C) or 6% (L) protein during pregnancy and lactation were maintained on a 17% casein (CC, n = 16 and LC, n = 17), 17% soybean flour (CS, n = 10 and LS, n = 10), or 6% casein (LL, n = 10) diet after weaning. The soybean diet reduced basal serum glucose (soybean diet, 5.6 ± 0.6 mmol/L vs. casein diet, 6.2 ± 0.6 mmol/L; p < 0.05) but increased alanine aminotransferase mRNA/GAPDH (soybean diet, 0.062 ± 0.038 vs. casein diet, 0.024 ± 0.011; p < 0.01), phosphoenolpyruvate carboxykinase mRNA/GAPDH (soybean diet, 1.53 ± 0.52 vs. casein diet, 0.95 ± 0.43; p < 0.05), and glycerokinase protein content (soybean diet, 0.86 ± 0.08 vs. casein diet, 0.75 ± 0.11; p < 0.05). The serum glucose concentration (recovered groups, 5.6 ± 0.5 mmol/L vs. control groups, 6.2 ± 0.7 mmol/L; p < 0.05) and phosphoenolpyruvate carboxykinase activity (recovered groups, 2.8 ± 0.6 μU/mg vs. control groups, 3.6 ± 0.6 μU/mg; p < 0.05) were decreased in rats subjected to protein restriction in early life. The glucose area under the curve during the pyruvate tolerance test did not differ among groups, whereas glucose area under the curve after glucagon infusion was reduced by early malnutrition (recovered groups, 4210 ± 572 mg/dL·40 min vs. control groups, 4493 ± 688 mg/dL·40 min; p < 0.001) and by the soybean diet (soybean diet, 3995 ± 500 mg/dL·40 min vs. casein diet, 4686 ± 576 mg/dL·40 min; p < 0.05). Thus, the soybean diet impaired the response to glucagon but did not alter gluconeogenesis.

Role of continuous glucose monitoring in the management of glycogen storage disorders.

Management of liver glycogen storage diseases (GSDs) primarily involves maintaining normoglycemia through dietary modifications and regular glucose monitoring. Self-monitoring of blood glucose is typically done 3-6 times per day, and may not sufficiently capture periods of asymptomatic hypoglycemia, particularly during sleep. Continuous glucose monitoring systems (CGMS) provide 24-h continuous glucose data and have been used effectively in diabetes mellitus to monitor metabolic control and optimize treatment. This is a relatively new approach in GSDs with only a handful of studies exploring this modality. In this study we used Dexcom CGMS to study the glycemic profile of 14 pediatric and six adult patients with GSD I, III, and IX. A total of 176days of CGMS data were available. The CGMS was found to be a reliable tool in monitoring glucose levels and trends at all times of the day with good concordance with finger-stick glucose values. This study revealed that in addition to overnight hypoglycemia, CGMS can uncover previously undetected, subclinical, low glucose levels during daytime hours. Additionally, the CGMS detected daytime and overnight hyperglycemia, an often overlooked concern in liver GSDs. The CGMS with concurrent dietary adjustments made by a metabolic dietitian improved metabolic parameters and stabilized blood glucose levels. The CGMS was found to be a safe, effective, and reliable method for optimizing treatment in patients with GSD I, III, and IX.

Glikojen Depolarının ve Sıvı Besin Alımının Egzersiz Sırasında Yağ ve Karbonhidrat Kullanımına Etkisi

Amaç: Açlık durumunun yağ metabolizmasını aktive ettiği iyi bilinmektedir. Bunun yanında son yıllarda, egzersize düşük kas glikojen depoları ile başlamanın normal duruma göre yağ metabolizmasını daha iyi aktive ettiği ve antrenmana daha fazla adaptasyon sağladığı ile ilgili çalışmalar artmıştır. Bu çalışma, düşük kas glikojen depoları ile egzersiz yapılmasının yağ metabolizmasını daha fazla etkileyip etkilemediğini test etmek için planlanmış ve yapılmıştır.&#x0D; Bireyler ve Yöntem: Araştırmaya 9 erkek, triatlon sporcusu katılmıştır. Bir hafta ara ile, kahvaltıda sıvı besin verilen veya aç (1 gece) durumda egzersiz denemeleri dengeli randomize, çapraz dizaynda gerçekleştirilmiştir. Çalışma öncesi tüm katılımcılar VO2 zirve ve zirve güç değerlerinin belirlenmesi için VO2 zirve testine katılmışlardır. Katılımcılar her iki durumda (Sıvı besin Egzersiz: SE1, SE2 ve Aç Egzersiz: AE1, AE2) %70 VO2 zirve’de 60 dk süren iki egzersiz denemesini 1 saat dinlenme aralığı ile yapmışlardır. Böylece ikinci egzersiz denemelerinin düşük kas glikojeni ile yapılması hedeflenmiştir.&#x0D; Bulgular: Toplam yağ oksidasyonu, SE1-SE2 (13.4±6.7 g/60 dk ve 23.9±7.6 g/60 dk, p&lt;0.001) ve SE1-AE2 (13.4±6.7 g/60 dk ve 27.4±6.0 g/60 dk, p=0.002) egzersizleri arasında anlamlı derecede artmıştır.&#x0D; Sonuç: Bu araştırma kapsamında bir gece açlık sonrası düşük kas glikojen depoları ile yapılan egzersizin sıvı besin alınan durumda yapılana göre yağ metabolizmasının arttırılmasında daha fazla bir etkinliğinin olmadığı belirlenmiştir. Bu bulgular, yağ metabolizmasındaki etkinliği arttıran esas belirleyici etmenin karaciğer glikojen depolarından çok kas glikojen depolarınının seviyesi olduğunu göstermektedir.

Cardiometabolic response of juvenile rainbow trout exposed to dietary selenomethionine

Selenium (Se) is considered an essential trace element, involved in important physiological and metabolic functions for all vertebrate species. Fish require dietary concentrations of 0.1–0.5 μg Se/g dry mass (d.m.) to maintain normal physiological and selenoprotein function, however concentrations exceeding 3 μg/g d.m. have been shown to cause toxicity. As Se is reported to have a narrow margin between essentiality and toxicity, there is growing concern surrounding the adverse effects of elevated Se exposure caused by anthropogenic activities. Previous studies have reported that elevated dietary exposure of fish to selenomethionine (Se-Met) can cause significant cardiotoxicity and alter aerobic metabolic capacity, energy homeostasis and swimming performance. The goal of this study aims to further investigate mechanisms of sublethal Se-Met toxicity, particularly potential underlying cardiovascular and metabolic implications of chronic exposure to environmentally relevant concentrations of dietary Se-Met in juvenile rainbow trout (Oncorhynchus mykiss). Juvenile rainbow trout were fed either control food (1.3 μg Se/g d.m.) or Se-Met spiked food (6.4, 15.8 or 47.8 μg Se/g d.m.) for 60 d at 3% body weight per day. Following exposure, ultrahigh resolution B-mode and Doppler ultrasound was used to characterize cardiac function in vivo. Chronic dietary exposure to Se-Met significantly increased stroke volume, cardiac output, and ejection fraction. Fish fed with Se-Met spiked food had elevated liver glycogen and triglyceride stores, suggesting impaired energy homeostasis. Exposure to Se-Met significantly decreased mRNA abundance of citrate synthase (CS) in liver and serpin peptidase inhibitor, clad H1 (SERPINH) in heart, and increased mRNA abundance of sarcoplasmic reticulum calcium ATPase (SERCA) and key cardiac remodelling enzyme matrix metalloproteinase 9 (MMP9) in heart. Taken together, these responses are consistent with a compensatory cardiac response to increased susceptibility to oxidative stress, namely a decrease in ventricular stiffness and improved cardiac function. These cardiac alterations in trout hearts were linked to metabolic disruption in other major metabolic tissues (liver and skeletal muscle), impaired glucose tolerance with increased levels of the toxic glucose metabolite, methylglyoxal, increased lipid peroxidation in skeletal muscle, development of cataracts and prolonged feeding behaviour, indicative of visual impairment. Therefore, although juvenile rainbow trout hearts were apparently able to functionally compensate for adverse metabolic and anti-oxidant changes after chronic dietary exposure Se-Met, complications associated with hyperglycemia in mammalian species were evident and would threaten survival of juvenile and adult fish.

Hypoinsulinemic hypoglycemia triggered by liver injury in elderly subjects with low body weight: case reports.

SummaryHypoglycemia is induced by many causes, especially over-dose of insulin or oral hypoglycemic agents in diabetic subjects. In such a case, hyperinsulinemic hypoglycemia is usually observed. On the other hand, it is important to classify secondary hypoglycemia and hypoinsulinemic hypoglycemia. Liver injury-induced hypoglycemia is one of the causes of hypoinsulinemic hypoglycemia but rarely observed in clinical practice. Herein, we experienced similar 2 cases of non-diabetic hypoinsulinemic hypoglycemia. Both of them were elderly subjects with low body weight. Furthermore, it is likely that hypoinsulinemic hypoglycemia in both subjects was triggered by severe liver injury, at least in part, due to possible limited liver glycogen store. In elderly subjects with low body weight and/or malnutrition, metabolism in the liver is reduced and glycogen accumulation is decreased. Such alteration brings out acute and marked liver injury, which finally leads to the onset of severe hypoglycemia. It is known that not only liver injury but also multiple organ failure could be induced due to extreme emaciation in subjects. It is likely that in elderly subjects with low body weight and/or malnutrition, multiple organ failure including liver failure could be induced due to the similar reason. Therefore, we should be very careful of such subjects in order to avoid the development of multiple organ failure which leads to life-threatening situations. In conclusion, we should keep in mind the possibility of hypoinsulinemic hypoglycemia when we examine severe liver injury, especially in elderly or starving subjects with low body weight and limited liver glycogen stores.Learning points:It is important to classify secondary hypoglycemia and hypoinsulinemic hypoglycemia.Liver injury-induced hypoglycemia is one of the causes of hypoinsulinemic hypoglycemia but rarely observed in everyday clinical practice.Herein, we reported similar 2 cases of hypoinsulinemic hypoglycemia without diabetes presumably triggered by severe liver injury.In both cases, hypoglycemia was improved by glucose infusion, although their liver injury was not improved.We should keep in mind the possibility of hypoinsulinemic hypoglycemia when we examine severe liver injury, especially in elderly subjects with low body weight.

Intermittent metabolic switching, neuroplasticity and brain health.

During evolution, individuals whose brains and bodies functioned well in a fasted state were successful in acquiring food, enabling their survival and reproduction. With fasting and extended exercise, liver glycogen stores are depleted and ketones are produced from adipose-cell-derived fatty acids. This metabolic switch in cellular fuel source is accompanied by cellular and molecular adaptations of neural networks in the brain that enhance their functionality and bolster their resistance to stress, injury and disease. Here, we consider how intermittent metabolic switching, repeating cycles of a metabolic challenge that induces ketosis (fasting and/or exercise) followed by a recovery period (eating, resting and sleeping), may optimize brain function and resilience throughout the lifespan, with a focus on the neuronal circuits involved in cognition and mood. Such metabolic switching impacts multiple signalling pathways that promote neuroplasticity and resistance of the brain to injury and disease.

Selectivity, cell permeability and oral availability studies of novel bromophenol derivative HPN as protein tyrosine phosphatase 1B inhibitor.

Protein tyrosine phosphatase 1B (PTP1B) negatively regulates insulin signalling by tyrosine dephosphorylation of the insulin receptor. It is a highly validated target for type 2 diabetes therapeutics. Here, the anti-diabetic effects of HPN were evaluated in the diabetic BKS db mice. The mode of inhibition of PTP1B by HPN was determined according to the Lineweaver-Burk plot. A surface plasmon resonance assay and molecular docking were used to study the interaction between HPN and PTP1B. C2C12 skeletal muscle cells were used to investigate the cell permeability of HPN and the effect of HPN on insulin signalling pathways. Long-term effects of HPN on glycaemic control were investigated in diabetic BKS db mice. Glycogen contents in liver and muscle were determined. Furthermore, changes in the number of beta cells were evaluated by Gomori staining. HPN was identified as a specific PTP1B inhibitor. HPN directly interacted with PTP1B by binding to the catalytic domain through hydrogen bonds in a competitive mode. Approximately 56.98% of HPN entered into the cultured C2C12 myotubes. HPN ameliorated the impaired insulin signalling in palmitate-treated C2C12 myocytes. Notably, oral administration of HPN significantly protected mice from hyperglycaemia, dyslipidemia and hyperinsulinaemia. HPN also enhanced the storage of glycogen in liver and muscle. Moreover, HPN obviously improved the beta cell numbers of the pancreatic islets. Our results indicate that HPN is a specific PTP1B inhibitor, with anti-diabetic properties and good cell permeability and oral availability.

Flipping the Metabolic Switch: Understanding and Applying the Health Benefits of Fasting.

Intermittent fasting (IF) is a term used to describe a variety of eating patterns in which no or few calories are consumed for time periods that can range from 12 hours to several days, on a recurring basis. Here we focus on the physiological responses of major organ systems, including the musculoskeletal system, to the onset of the metabolic switch – the point of negative energy balance at which liver glycogen stores are depleted and fatty acids are mobilized (typically beyond 12 hours after cessation of food intake). Emerging findings suggest the metabolic switch from glucose to fatty acid-derived ketones represents an evolutionarily conserved trigger point that shifts metabolism from lipid/cholesterol synthesis and fat storage to mobilization of fat through fatty acid oxidation and fatty-acid derived ketones, which serve to preserve muscle mass and function. Thus, IF regimens that induce the metabolic switch have the potential to improve body composition in overweight individuals. Moreover, IF regimens also induce the coordinated activation of signaling pathways that optimize physiological function, enhance performance, and slow aging and disease processes. Future randomized controlled IF trials should use biomarkers of the metabolic switch (e.g., plasma ketone levels) as a measure of compliance and the magnitude of negative energy balance during the fasting period.

Ethanol metabolism varies with hypoxia tolerance in ten cyprinid species.

During periods of severe hypoxia or anoxia, Carassius spp. are known for their ability to produce ethanol as their anaerobic end product, which diffuses into the environment thereby reducing the osmotic and acidotic load associated with "anaerobic" glycolysis. However, the relationship between alcohol dehydrogenase (ADH) and acetaldehyde dehydrogenase (ALDH) activities, key ethanol metabolizing enzymes, and hypoxia tolerance among Carassius spp. and their closely related non-ethanol-producing cyprinids remains unclear. To address this, we quantified the activity levels of key anaerobic enzymes in liver and muscle in species of cyprinids over 48h of severe hypoxia exposure (0.7kPa). As predicted, muscle ADH activity was highest in the two most hypoxia-tolerant species (Carassius spp.), with very low levels present in the other species examined. However, liver ADH activities showed an inverse relationship with hypoxia tolerance, with the most hypoxia-tolerant fish having the lowest ADH activity. There was no correlation between hypoxia tolerance and ALDH and LDH activities in muscle or liver. All species produced lactate, reaching their highest levels after 8h, but returning to near-baseline levels by 48h of sustained exposure to hypoxia, suggesting lactate oxidation or depressed ATP demand. Liver glycogen content was not affected by 48h hypoxia exposure in the most hypoxia-tolerant species, whereas the least tolerant species consumed the majority of the liver glycogen stores, which is probably due to the greater relative hypoxia exposure experienced by these species. Our findings that liver ADH activities were inversely related to hypoxia tolerance suggests that in all but Carassius spp., the ethanol metabolizing pathways in cyprinids is largely similar to that observed in other vertebrates and plays a role in the detoxification of ethanol. Furthermore, conservation of glycogen stores may be the result of metabolic-depressing pathways in the more tolerant species, regardless of the ability to produce ethanol, or adaptations that improve oxygen uptake to reduce metabolic demands due to hypoxia.

Inclusion of avocado (Persea americana) seeds in the diet to improve carbohydrate and lipid metabolism in rats

The effects of avocado seeds (A) inclusion (2%, 4% and 8%) in diets on cholesterol and carbohydrate metabolism in normal rats Sprague Dawley (SD) fed on basal diet (BD) or high sucrose diet (HSD) and spontaneous hypertensive rats (SHR) fed on BD were studied. The inclusion of avocado seeds in the diet influences the feeding and growth performance in rats. The inclusion of A lowered (p<0.05) cholesterol at 2% and 4% doses and glucose at 2% in serum of SD rats fed on BD, whereas only serum cholesterol level was reduced at all the three doses in SHR. Increased liver glycogen (p<0.05) was noted in SD rats fed on BD with 8% A. All avocado seeds doses increased (p<0.05) liver glycogen storage in SHR fed on BD and SD rats fed on HSD. Avocado seeds can lower blood glucose and cholesterol and enhance liver glycogen storage in rats.

Gluconeogenesis during starvation and refeeding phase is affected by previous dietary carbohydrates levels and a glucose stimuli during early life in Siberian sturgeon (Acipenser baerii).

Gluconeogenesis responses was assessed during a short starvation period and subsequent refeeding in Siberian sturgeon (Acipenser baerii) previously fed different dietary carbohydrates levels and experienced to a glucose stimuli during early life. The sturgeon larvae were previously fed either a high glucose diet (G) or a low glucose diet (F) from the first feeding to yolk absorption (8 to 12 d post-hatching [dph]). Each group of fish was sub-divided into 2 treatments at 13 dph and was fed either a high-carbohydrate diet (H) or a low carbohydrate diet (L) until 20 wk. In the current study, the fish in 4 groups (GL, FL, GH and FH) were experienced to starvation for 21 d following by re-feeding of their corresponding diets for 21 d. Fish were sampled at postprandial 6 and 24 h before starvation (P6h and P24h), starvation 7, 14 and 21 d (S7, S14 and S21) and 1, 7, 14 and 21 d during refeeding (R1, R7, R14 and R21). Plasma samples during refeeding were taken at P6h at each time point. Glycaemia levels, liver and muscle glycogen contents, activities and mRNA levels of hepatic gluconeogenic enzymes were examined. We found that both dietary carbohydrate levels and early glucose stimuli significantly affected the metabolic responses to starvation and refeeding in Siberian sturgeon (P < 0.05). During prolonged starvation, Siberian sturgeon firstly mobilized the liver glycogen and then improved gluconeogenesis when the dietary carbohydrates were abundant, whereas preserved the liver glycogen stores at a stable level and more effectively promoted gluconeogenesis when the dietary carbohydrates are absent to maintain glucose homoeostasis. During refeeding, as most teleostean, Siberian sturgeon failed controlling the activities and mRNA levels of phosphoenolpyruvate carboxykinase cytosolic forms (PEPCK-C), fructose-1,6-bisphosphatase (FBPase), but particularly controlled phosphoenolpyruvate carboxykinase mitochondrial forms (PEPCK-M) activities and mRNA expression of glucose-6-phosphatase (G6Pase, except in GL group). Siberian sturgeon has a full compensatory ability on growth, but this ability would be obstructed by early glucose stimuli when refeeding the low carbohydrate diet after S21.

Euglycemic Diabetic Ketoacidosis: A Review.

Diabetic ketoacidosis (DKA) is one of the most serious complications of diabetes. It is characterised by the triad of hyperglycemia (blood sugar >250 mg/dl), metabolic acidosis (arterial pH <7.3 and serum bicarbonate <18 mEq/L) and ketosis. Rarely these patients can present with blood glucose (BG) levels of less than 200 mg/dl, which is defined as euglycemic DKA. The possible etiology of euglycemic DKA includes the recent use of insulin, decreased caloric intake, heavy alcohol consumption, chronic liver disease and glycogen storage disorders. DKA in pregnancy has also been reported to present with euglycemia. The recent use of sodium glucose cotransporter 2 (SGLT2) inhibitors has shed light on another possible mechanism of euglycemic DKA. Clinicians may also be misled by the presence of pseudonormoglycemia. Euglycemic DKA thus poses a challenge to physicians, as patients presenting with normal BG levels in ketoacidosis may be overlooked, leading to a delay in appropriate management strategies. In this article, we review all the possible etiologies and the associated pathophysiology of patients presenting with euglycemic DKA. We also discuss the approach to diagnosis and management of such patients. Despite euglycemia, ketoacidosis in diabetic patients remains a medical emergency and must be treated in a quick and appropriate manner.

Muscles in diabetes

Muscles in diabetes

Bone marrow stem cell therapy partially ameliorates pathological consequences in livers of mice expressing mutant human α1‐antitrypsin

These results suggest that BM stem cell transplantation may be a promising therapy for AATD-related liver disease. (Hepatology 2017;65:1319-1335).