Blood Glucose Supply Research Articles

Whole-Exome sequencing identifies GYS2 biallelic variants in individuals with suspected epilepsy

BackgroundAdequate glucose supply is essential for brain function, therefore hypoglycemic states may lead to seizures. Since blood glucose supply for brain is buffered by liver glycogen, an impairment of liver glycogen synthesis by mutations in the liver glycogen synthase gene (GYS2) might result in a substantial neurological involvement. Here, we describe the phenotypes of affected siblings of two families harboring biallelic mutations in GYS2. MethodsTwo suspected families - a multiplex Pakistani family (family A) with three affected siblings and a family of Moroccan origin (family B) with a single affected child who presented with seizures and reduced fasting blood glucose levels were genetically characterized. Whole exome sequencing (WES) was performed on the index patients, followed by Sanger sequencing-based segregation analyses on all available members of both families. ResultsThe variant prioritization of WES and later Sanger sequencing confirmed three mutations in the GYS2 gene (12p12.1) consistent with an autosomal recessive pattern of inheritance. A homozygous splice acceptor site variant (NM_021957.3, c. 1646 -2A>G) segregated in family A. Two novel compound heterozygous variants (NM_021957.3: c.343G>A; p.Val115Met and NM_021957.3: c.875A>T; p.Glu292Val) were detected in family B, suggesting glycogen storage disorder. A special diet designed to avoid hypoglycemia, in addition to change of the anti-seizure medication led to reduction in seizure frequency. ConclusionsThis study suggests that the seizures in patients initially diagnosed with epilepsy might be directly caused, or influenced by hypoglycemia due to pathogenic variants in the GYS2 gene.

A Challenge To Treat Hypoglycemia For The Diabetic Elderly Patient In Daily Clinical Practice

Background: Hypoglycemia is an acute complication that often occurs in daily clinical practice. The incidence of hypoglycemia is increased, one of which is by age factors and the use of insulin. 
 Case Presentation: A 66-years old Indonesian woman with obesity (BMI=35.2 kg/m2) came to Emergency Department (ED) with decreased of consciousness due to a skipped meal after a prandial insulin injection with errors in calculating insulin dose. She had Diabetes Mellitus type 2 since 10 years ago and got insulin prescription since last year. The random blood sugar (RBG) was 27 mg/dl. Patient was administered intravenous D40% 75ml and the symptoms was improved. Patient was diagnosed this patient with severe hypoglycemia. During hospitalization, patient’s blood sugar had fluctuation in 2 days consecutive mornings and began to stable in day 3 on ward. When the patient discharged, we prescribed 24U basal insulin given before bed if the RBG level >200mg/dl. 
 Discussion: In older population, the neuroglycopenic symptoms, such as lethargy, dizziness, and delirium appear in higher BG level than the autonomic symptoms. The disproportion of demand and supply of blood glucose in the brain causes the neuroglycopenic symptoms. In addition, those signs are also likely to be misinterpreted as signs of stroke, dementia, or vision problems. This cycle of misidiagnosed and the tendency of neuroglypenic symptoms lead the older population into hypoglycemia unawareness. 
 Conclusion: Hypoglycemia unawareness is one of the warning signs of the severity of Diabetes Mellitus type 2 caused by multiple factors which has high prevalence in the elderly. Therefore, particular management is needed in this population by selecting the suitable glucose-lowering agent considering individualized patient preferences rather than focusing on the glycemic target.

Cognitive cost as dynamic allocation of energetic resources.

While it is widely recognized that thinking is somehow costly, involving cognitive effort and producing mental fatigue, these costs have alternatively been assumed to exist, treated as the brain's assessment of lost opportunities, or suggested to be metabolic but with implausible biological bases. We present a model of cognitive cost based on the novel idea that the brain senses and plans for longer-term allocation of metabolic resources by purposively conserving brain activity. We identify several distinct ways the brain might control its metabolic output, and show how a control-theoretic model that models decision-making with an energy budget can explain cognitive effort avoidance in terms of an optimal allocation of limited energetic resources. The model accounts for both subject responsiveness to reward and the detrimental effects of hypoglycemia on cognitive function. A critical component of the model is using astrocytic glycogen as a plausible basis for limited energetic reserves. Glycogen acts as an energy buffer that can temporarily support high neural activity beyond the rate supported by blood glucose supply. The published dynamics of glycogen depletion and repletion are consonant with a broad array of phenomena associated with cognitive cost. Our model thus subsumes both the “cost/benefit” and “limited resource” models of cognitive cost while retaining valuable contributions of each. We discuss how the rational control of metabolic resources could underpin the control of attention, working memory, cognitive look ahead, and model-free vs. model-based policy learning.

Sarapan dan jajan berhubungan dengan kemampuan konsentrasi pada remaja

Background: Adolescence is a phase that a human has to pass through in life to become an adult. Bureau of Statistical Centre (1999) reported that total number of adolescent people from 10-19 years old group in Indonesia is about 22% of its total population. High school adolescent often does not have breakfast due to many different reasons such as being in a hurry when going to the school. Breakfast is able to provide carbohydrate for increasing blood glucose supply. In a normal blood glucose supply, passion and concentration as a student would be better so that it makes positive impact to raise productivity.Objective: This study aimed to define correlation between breakfast and have snack at break time habit with concentration capability on high school adolescent in Palangka Raya city.Method: This study was an observational research in cross sectional design. The number of research subject for prevalence test were 106 students for not breakfast group which in screening result were not in anemic condition, while for hypothesis test the mean difference for the two independent groups the total number of subject were 80 persons that consist of 40 subjects for breakfast group and 40 subjects for not breakfast group. Data collection was obtained from body weight and height measurement to explore nutritional status; food recall method to give information of breakfast and have snack at break time, energy, carbohydrate, protein and fat intake; digit symbol and digit span test to explore concentration capability to visual and audio information. The data was processed and analyzed in analytic descriptive way using Spearman correlation test and t-test.Results: This study indicated that 37.7% - 38.8% adolescent in SMAN 1 Pahandut Palangka Raya did not have breakfast. Analytical statistic result showing adolescent who has breakfast has significantly higher concentration capability (using digit symbol and digit span test) than adolescent group who did not have breakfast (p<0.05). Having snack at break time adolescent group had significantly higher concentration capability by using digit symbol test than adolescent group who did not have snack at break time (p<0.05).Conclusion: There was correlation between breakfast and have snack at break time with concentration capability on high school adolescent.

Symptomatic Hypoglycemia Causing Brain Injury in a Term Breast Fed Newborn Following Early Discharge

Cerebral metabolism and functioning depends upon an adequate blood glucose supply which provides for majority of the brain's energy requirement. Studies from the past have shown that neonatal hypoglycemia is associated with acute and long term neurological sequelae. Early discharge without adequately established breast feeding may lead to feeding problems, post discharge hypoglycemia and its associated neurological complications. The authors describe one such case of an exclusively breast fed term newborn who presented on day 3 with symptomatic hypoglycemia and associated neurological injury.

Hypoglycemia leads to age-related loss of vision

The retina is among the most metabolically active tissues in the body, requiring a constant supply of blood glucose to sustain function. We assessed the impact of low blood glucose on the vision of C57BL/6J mice rendered hypoglycemic by a null mutation of the glucagon receptor gene, Gcgr. Metabolic stress from moderate hypoglycemia led to late-onset loss of retinal function in Gcgr(-/-) mice, loss of visual acuity, and eventual death of retinal cells. Retinal function measured by the electroretinogram b-wave threshold declined >100-fold from age 9 to 13 months, whereas decreases in photoreceptor function measured by the ERG a-wave were delayed by 3 months. At 10 months of age Gcgr(-/-) mice began to lose visual acuity and exhibit changes in retinal anatomy, including an increase in cell death that was initially more pronounced in the inner retina. Decreases in retinal function and visual acuity correlated directly with the degree of hypoglycemia. This work demonstrates a metabolic-stress-induced loss of vision in mammals, which has not been described previously. Linkage between low blood glucose and loss of vision in mice may highlight the importance for glycemic control in diabetics and retinal diseases related to metabolic stress as macular degeneration.

A hypothesis on the biochemistry of spontaneous remissions of cancer: coupling of oxidative phosphorylation and the remission of cancer.

Aggressively growing tumors are highly dependent on the blood glucose supply. Whenever the blood glucose supply is high they grow rapidly and whenever the blood glucose supply is low they grow slowly. In cases of bonafide reports of spontaneous remissions and regressions of cancer, this tumor regulatory mechanism fails and the tumor grows rapidly and steadily despite a low blood glucose supply. This results in the collapse of the tumor system and its removal by the immune system. In lay language, it can be compared to a car that can be driven safely at 60 mph, but if it is driven at 200 mph, it will turn over and stop. Accelerated tumor growth can be induced in many ways such as: (a) reducing tumor mass which will result in a compensatory tumor growth; (b) administering hormones; (c) increasing body temperature; (d) reducing blood cortisol level; and (e) temporarily suppressing cellular immunity. A simple example would be a case of a patient with advanced and widespread cancer. If the tumor mass is reduced at once it will result in compensatory tumor growth and if hypoglycemia is initiated just prior to reducing the tumor mass and the hypoglycemia is maintained, it could possibly be followed with a brief tumor growth and the remission of cancer. The suggested procedure has not been tested or proven to be correct as yet; it is not recommended unless done under careful supervision.

Preischemic blood glucose supply to the brain modulates HSP 72 synthesis and neuronal damage in gerbils

Preischemic hyperglycemia is known to aggravate brain damage caused by transient forebrain ischemia. Because heat shock proteins (HSPs) 72 have been proposed to play a protective role against ischemic neuronal injury, we studied the HSP 72 mRNA expression and protein synthesis in gerbils subjected to 10 min bilateral carotid occlusion under normoglycemic, hyperglycemic and fasting conditions. HSP 72 mRNA expression and HSP 72 synthesis were studied using in situ hybridization and immunostaining, respectively. After 8 h of blood recirculation, HSP 72 mRNAs were expressed in all the hippocampal subfields of the three different groups, with higher expression in the hyperglycemic gerbils. After 48 h of reperfusion, HSP 72 mRNAs had almost completely disappeared in the hyper- and normoglycemic groups, and were more strongly expressed in the CA 1 neurons of the fasted group. At this time, fasted gerbils exhibited intense HSP 72 immunoreactivity in the CA 1, whereas an absence of immunoreactivity was observed in that area in the other groups. Finally, ischemia was also associated with marked astrocytic activation, as evidenced by GFAP immunostaining. Overall results indicate that preischemic differences in blood glucose supply to the brain are related to HSP 72 mRNA expression (in terms of duration) and to HSP 72 protein induction (in terms of intensity) in the vulnerable CA 1 neurons of the hippocampus. Ability of CA 1 neurons to synthesize HSP 72 proteins was associated with higher neuronal survival in the fasted group after 48 h of reflow, suggesting a protective role of HSP 72, even though evaluation of neuronal damage at 7 days indicated that neuronal death was mainly delayed in the time.

2 Interactions Between Muscle Glycogen and Blood Glucose during Exercise

Muscle glycogen and blood glucose are important substrates for contracting skeletal muscle during exercise. The possibility exists for considerable interaction between muscle glycogen and blood glucose and their effects on muscle glucose uptake and glycogenolysis, respectively. Increases in blood glucose availability have little effect on net muscle glycogen utilization during prolonged, strenuous cycling exercise, but this may be dependent upon the mode and intensity of exercise. No data exist on the direct effect of reduced blood glucose levels on muscle glycogen metabolism. In rats, studies using the perfused hindlimb suggest an inverse relationship between muscle glycogen levels and glucose uptake. A similar conclusion can be drawn from a number of human studies albeit, on occasion, from indirect evidence. The influence of muscle glycogen on glucose uptake involves effects on both membrane glucose transport and intracellular glucose metabolism. Such a relationship would, under conditions of adequate muscle glycogen availability, limit muscle glucose uptake, thereby preserving the relatively small blood glucose supply for the brain, nerves, and blood cells, which are dependent on it for their energy metabolism.

Carbohydrate and fluid ingestion during exercise

Intense exercise (i.e.; above 60% VO2max) can be maintained for prolonged periods provided sufficient carbohydrate is available for energy and the heat generated from muscle metabolism does not cause excessive hyperthermia and/or dehydration due to sweating. It is clear that people should ingest carbohydrate during prolonged exercise (i.e.; longer than 1-2 h), which causes fatigue because of an inadequate supply of blood glucose and that fluids should also be ingested in an attempt to offset dehydration and reduce hyperthermia. Ingestion of approximately 30-60 g of carbohydrate (i.e.; glucose, sucrose, or starch) during each hour of exercise will generally be sufficient to maintain blood glucose oxidation late in exercise and delay fatigue. Since the average rates of gastric emptying and intestinal absorption can reach 1 l.h-1 for water and solutions containing up to 8% carbohydrate, exercising people can be supplemented with both carbohydrate and fluids at relatively high rates (over 60 g.h-1 of carbohydrate and 1 l.h-1 of fluid). Therefore, when sweat rate is not high (i.e.; less than 1 l.h-1), the addition of carbohydrate to fluids, and vice versa, does not prevent adequate supplementation of each, especially if large volumes are consumed to keep the stomach somewhat full and thus increase gastric emptying. Therefore, in most situations there are no trade-offs between fluid and carbohydrate.(ABSTRACT TRUNCATED AT 250 WORDS)

Influence of carbohydrate-restricted versus calorie-restricted diets on rat placental glycogen

Maternal blood glucose is the principle metabolic fuel for the developing placenta and fetus, and is the precursor for the large glycogen reserves that accumulate in the placenta and fetal liver during gestation. In this study we investigated whether maternal dietary glucose restriction would lead to lowered placental glycogen levels and compromised fetal growth. Pregnant rat dams were fed a carbohydrate-free (0% glucose) diet, which was compared to either a calorie-restricted pair fed or ad libitum control (62% glucose) group. Results demonstrated that a dietary glucose restriction produced statistically significant reductions in total placental glycogen and fetal weight but not placental size or glycogen concentration. It is suggested that restrictions in dietary glucose during the period of glycogen accumulation lower the maternal postprandial blood glucose supply sufficiently to reduce total placental glycogen levels. This reduction in total placental glycogen is associated with retarded fetal growth.

Rapid, transient drop in brain glucose after intravenous phloretin or 3-0-methyl-D-glucose.

Rats were injected intravenously with either phloretin (100 mg/kg) or 3-0-methyl glucose (2 g/kg) to reduce the carrier-mediated flux of glucose into brain. Plasma glucose and brain free glucose (BFG), lactate, and glycogen were measured over a 16 min time course. Injection of these substances caused a rapid drop in BFG to 60% of control at one minute and a minimum (50% of control values) at 4 min., followed by a gradual rise to control levels at 16 min. While plasma glucose fell, and then increased after injection, brain lactate and glycogen content was unaffected. Repeated injections of phloretin eventually caused a drop in brain glycogen; but with either competitor, BFG never fell below 50% of normal values. The i.v. injection of the glucose analog, 3-0-methyl glucose (the less toxic of the two drugs) is proposed as a possible means of cutting off the potentially hazardous supply of blood glucose to the postischemic brain.

Effect of substrate supply and beta-adrenergic blockade on heart glycogen and triglyceride utilization during exercise in the rat.

Exercise-induced heart glycogen and triglyceride mobilization was studied in control rats, in rats with reduced blood glycose supply (fasted rats), in rats with reduced plasma free fatty acids (FFA) supply (nicotinic acid-treated rats), and in rats with blockade of beta-adrenergic receptors (propranolol-treated rats). It was found in the fed control rats that both the heart glycogen and triglyceride levels were reduced at the beginning of the exercise and thereafter they returned to the control level despite the exercise being continued. The triglyceride level was reduced again during the exhaustive exercise. Reduced blood glucose supply increased the heart glycogen and triglyceride utilization during exercise. Partial prevention of the plasma FFA elevation during exercise increased the heart glycogen utilization and had no effect on utilization of the heart triglycerides. Blockade of the beta-adrenergic receptors fully prevented both the heart glycogen and triglyceride mobilization during exercise.

Glucose 6-phosphatase activity in kidney of the river lamprey ( Lampetra fluviatilis L.)

The highest activity of glucose 6-phosphatase is found in the kidney of the lamprey, indicating that this organ could be the main organ for blood glucose supply and regulation.

The influence of diet on response to hemorrhagic shock.

Prior nutrition is known to influence tolerance to hypovolemic shock. This study was undertaken to determine the influence of dietary composition on the response of animals subjected to hypovolemic shock. Particular attention was directed to the role of high and low protein diet content with a proportionate change in carbohydrate content to yield isocaloric diets. Rats were placed on one of three diets and were subsequently subjected to shock either by 1) hemorrhage to a pre-determined mean arterial blood pressure, or by 2) hemorrhage of a pre-determined volume of blood based on per cent of body weight. Serial measurements were made of blood pressure, blood volume removed, survival time,hematocrit, blood glucose, pH and blood gases. The results indicate that a high protein diet does not prolong tolerance to recurrent blood loss but there is a greatly reduced tolerance to hemorrhage shock in rats whose body weight was maintained on a low protein/high carbohydrate diet. The latter animals also exhibited impaired refill of plasma volume and a paradoxical, continuing hyperglycemic response during hypovolemia. This study suggests that although an abundant supply of blood glucose is available as an energy source, glucose uptake in the peripheral tissues is inhibited during hypovolemia by unknown mechanisms and thus homeostasis is curtailed. The protein content of the diet may be a critical factor in carbohydrate use during shock.

Sources of blood glucose in the rat fetus.

Extract: Pregnant Sprague-Dawley rats from the 18th to the 21st day of gestation were fasted for 16 hr and anesthetized, and a constant infusion of uniformly labeled glucose-14C and of glucose-2-3H was started. The purpose was to see if the regulation of fetal blood glucose concentration differed from the maternal during fasting. The results are given in Figures 2 and 3. During the course of the infusions, the specific activity of glucose was, at all points measured, two to four times lower in the fetal than in the maternal serum. The higher fetal than maternal supply of blood glucose could be derived either from gluconeogenesis or from glycogenolysis in the fetus. In vitro studies indicate that the fetal rat liver is unable to perform gluconecgenesis. Therefore, the placenta was investigated for the presence of a gluconeogenetic pathway. Placenta slices showed no ability to convert pyruvate into glucose (Fig. 8). No phosphoenolpyruvate carboxykinase (EC. 4.1.1.32) activity could be found in placenta homogenates. The possibility of the presence of gluconeogenesis in the rat fetus has been investigated in vivo. Intraperitoneal injections of pyruvate-2-14C and glycerol-1, 3-14C were given to 1-day-old newborns, prematures (fetuses which were delivered 1 day prior to term), and fetuses in situ. The 1-day-old newborns do convert both substrates to glucose, with averages of 50 and 70%, respectively, of serum radioactivity being due to glucose-14C, thus proving the validity of this way of investigating gluconeogenesis in vivo. The prematures did not synthesize glucose from pyruvate, but glucose synthesis occurred from glycerol, an average of 70% of serum radioactivity being due to glucose-14C. The fetuses which were injected in situ did not synthesize glucose from either one of the two substrates. These experiments would seem to exclude fetal gluconeogenesis as the source of fetal blood glucose in the constant infusion experiments mentioned above. Fetal hepatic glycogenolysis can account only in part for the higher dilution of the specific activity of glucose in the fetus after a 16-hr fast. The data in Table I show that at the time when the constant infusions were started (after a 16-hr fast) the fetal liver glycogen concentration had diminished from 111 ± 5 to 82 ± 10 mg/g wet weight, as compared to the fed state. This decrease is too small to account for the higher fetal than maternal dilution of blood glucose specific activity, or for the maintenance of unchanged blood glucose levels in the fetus after a 16-hr fast (86 ± 8 and 92 ± 11 mg/100 ml, respectively). An unknown mechanism leading to the privileged situation of the fetus with regard to blood glucose levels during a fasting state must be postulated. Speculation: Gluconeogenesis is inactive in the rat fetus, as investigated by in vivo and in vitro methods. Fetal hepatic glycogenolysis cannot be the only source of fetal blood glucose during fasting.

Effects of Ethanol on Glucose Utilization in Rat Brain

SummarySigns of impairment of utiliztion of glucose in rat brains at 2 1/2 hr after administration of ethanol included increased glucose ratios for cerebrum/blood and hind-brain/blood in fed and fasted rats, decreased concentrations of lactate in cerebrum and hindbrain in fed rats, higher percentages of brain 14C in glucose at 15 min after injection of glucose-U-14C, and decreases in blood glucose equivalents in the combined glucose metabolites in cerebrum and hindbrain of fed and fasted rats.Glucose uptake in cerebrum and hindbrain was lower in rats given ethanol by stomach tube (fed or fasted) than in control rats. Glucose uptake was normal in fed rats given ethanol intraperitoneally, but they had increased blood glucose concentrations. However, in these rats with the greater supply of blood glucose the greatest decreases in blood glucose equivalents of brain glucose metabolites were found. Significant decreases were found in aspartate, glutamate, glutamine, and γ-aminobutyrate (GABA).Effects of fasting...