scholarly journals Cerebral glycogen in humans following acute and recurrent hypoglycemia: Implications on a role in hypoglycemia unawareness

2016 ◽  
Vol 37 (8) ◽  
pp. 2883-2893 ◽  
Author(s):  
Gülin Öz ◽  
Mauro DiNuzzo ◽  
Anjali Kumar ◽  
Amir Moheet ◽  
Ameer Khowaja ◽  
...  

Supercompensated brain glycogen levels may contribute to the development of hypoglycemia-associated autonomic failure (HAAF) following recurrent hypoglycemia (RH) by providing energy for the brain during subsequent periods of hypoglycemia. To assess the role of glycogen supercompensation in the generation of HAAF, we estimated the level of brain glycogen following RH and acute hypoglycemia (AH). After undergoing 3 hyperinsulinemic, euglycemic and 3 hyperinsulinemic, hypoglycemic clamps (RH) on separate occasions at least 1 month apart, five healthy volunteers received [1-13C]glucose intravenously over 80+ h while maintaining euglycemia. 13C-glycogen levels in the occipital lobe were measured by 13C magnetic resonance spectroscopy at ∼8, 20, 32, 44, 56, 68 and 80 h at 4 T and glycogen levels estimated by fitting the data with a biophysical model that takes into account the tiered glycogen structure. Similarly, prior 13C-glycogen data obtained following a single hypoglycemic episode (AH) were fitted with the same model. Glycogen levels did not significantly increase after RH relative to after euglycemia, while they increased by ∼16% after AH relative to after euglycemia. These data suggest that glycogen supercompensation may be blunted with repeated hypoglycemic episodes. A causal relationship between glycogen supercompensation and generation of HAAF remains to be established.

2011 ◽  
Vol 32 (2) ◽  
pp. 256-263 ◽  
Author(s):  
Gülin Öz ◽  
Nolawit Tesfaye ◽  
Anjali Kumar ◽  
Dinesh K Deelchand ◽  
Lynn E Eberly ◽  
...  

Supercompensated brain glycogen may contribute to the development of hypoglycemia unawareness in patients with type 1 diabetes by providing energy for the brain during periods of hypoglycemia. Our goal was to determine if brain glycogen content is elevated in patients with type 1 diabetes and hypoglycemia unawareness. We used in vivo13C nuclear magnetic resonance spectroscopy in conjunction with [1-13C]glucose administration in five patients with type 1 diabetes and hypoglycemia unawareness and five age-, gender-, and body mass index-matched healthy volunteers to measure brain glycogen content and metabolism. Glucose and insulin were administered intravenously over ∼51 hours at a rate titrated to maintain a blood glucose concentration of 7 mmol/L. 13C-glycogen levels in the occipital lobe were measured at ∼5, 8, 13, 23, 32, 37, and 50 hours, during label wash-in and wash-out. Newly synthesized glycogen levels were higher in controls than in patients ( P<0.0001) for matched average blood glucose and insulin levels, which may be due to higher brain glycogen content or faster turnover in controls. Metabolic modeling indicated lower brain glycogen content in patients than in controls ( P=0.07), implying that glycogen supercompensation does not contribute to the development of hypoglycemia unawareness in humans with type 1 diabetes.


1998 ◽  
Vol 44 (1) ◽  
pp. 40-42
Author(s):  
I. P. Grigoriev

The author hypothesizes a probable causative role of alteration of ascorbic acid concentration in the brain in the development of mental disease in diabetics. In order to verify this hypothesis, ascorbic acid was measured in the brain cortex of rats 21 days after induction of streptozotocin diabetes or 1 h after intraperitoneal injection of glucose in a dose of 5 g/kg. Ascorbic acid level was increased both in diabetes (456+26 yg/g tissue versus 415+37 \vg/g in the control, p<0.01) and in acute hyperglycemia (475+54 \tg/g versus 406+65 \xg/g in the control, p<0.001). This confirmed that changed concentration of ascorbic acid in the brain can promote the development of a mental disease in diabetics. In the liver the concentration of ascorbic acid was decreased in streptozotocin diabetes (by 17%), p<0.001) and increased in acute hypoglycemia (by 24%, p<0.01). The findings permit us to hypothesize that hypoglycemia inhibits the production of ascorbic acid from the liver to the blood in rats and impedes the transport of ascorbic acid through the gut wall into the blood in humans.


2020 ◽  
Vol 105 (11) ◽  
Author(s):  
Eric Lontchi-Yimagou ◽  
Sandra Aleksic ◽  
Raphael Hulkower ◽  
Rebekah Gospin ◽  
Akankasha Goyal ◽  
...  

Abstract Background Recurrent hypoglycemia blunts counter-regulatory responses to subsequent hypoglycemic episodes, a syndrome known as hypoglycemia-associated autonomic failure (HAAF). Since adrenergic receptor blockade has been reported to prevent HAAF, we investigated whether the hypoglycemia-associated rise in plasma epinephrine contributes to pathophysiology and reported interindividual differences in susceptibility to HAAF. Methods To assess the role of hypoglycemia-associated epinephrine responses in the susceptibility to HAAF, 24 adult nondiabetic subjects underwent two 2-hour hyperinsulinemic hypoglycemic clamp studies (nadir 54 mg/dL; 0-2 hours and 4-6 hours) on Day 1, followed by a third identical clamp on Day 2. We challenged an additional 7 subjects with two 2-hour infusions of epinephrine (0.03 μg/kg/min; 0-2 hours and 4-6 hours) vs saline on Day 1 followed by a 200-minute stepped hypoglycemic clamp (90, 80, 70, and 60 mg/dL) on Day 2. Results Thirteen out of 24 subjects developed HAAF, defined by ≥20% reduction in average epinephrine levels during the final 30 minutes of the third compared with the first hypoglycemic episode (P &lt; 0.001). Average epinephrine levels during the final 30 minutes of the first hypoglycemic episode were 2.3 times higher in subjects who developed HAAF compared with those who did not (P = 0.006). Compared to saline, epinephrine infusion on Day 1 reduced the epinephrine responses by 27% at the 70 and 60 mg/dL glucose steps combined (P = 0.04), with a parallel reduction in hypoglycemic symptoms (P = 0.03) on Day 2. Conclusions Increases in plasma epinephrine reproduce key features of HAAF in nondiabetic subjects. Marked interindividual variability in epinephrine responses to hypoglycemia may explain an individual’s susceptibility to developing HAAF.


2021 ◽  
Vol 12 ◽  
Author(s):  
Luping Zhang ◽  
Jinwen Huang ◽  
Zhengxiang Zhang ◽  
Zhijian Cao

Background: Although there have been many magnetic resonance spectroscopy (MRS) studies of migraine, few have focused on migraines during an attack. Here, we aimed to assess metabolite changes in the brain of patients with migraine, both during an attack and in the interictal phase.Methods: Six patients (one man and five women, mean age: 39 ± 10 years) with migraine without aura during the attack (MWoA-DA), 13 patients (three men and 10 women, mean age: 31 ± 9 years) with migraine without aura during the interictal period (MWoA-DI), and 13 healthy controls (HC) (four men and nine women, mean age: 31 ± 9 years) were studied. All subjects underwent an MRS examination focusing on the occipital lobe. Metabolite changes were investigated among three groups.Results: The MWoA-DA patients had lower glutathione/total creatine ratio (GSH/tCr) than the MWoA-DI patients and HC. Furthermore, MWoA-DI patients showed lower total choline/total creatine ratio (tCho/tCr) than those in the other two groups. The GSH/tCr ratio was positively correlated with attack frequency in the MWoA-DI group. The tCho/tCr ratio was positively correlated with attack frequency and Migraine Disability Assessment Scale (MIDAS) scores in the MWoA-DA group.Conclusion: The present study suggests the existence of distinct pathophysiological states between the MWoA-DA and MWoA-DI groups. Neuronal dysfunction is a possible predisposing factor for migraine attack onset, along with oxidative stress and inflammation.


2019 ◽  
Vol 5 (1) ◽  
pp. 16-22
Author(s):  
Mohammad Ali Nazari ◽  
◽  
Javad Salehi Fadardi ◽  
Zohreh Gholami Doborjeh ◽  
Taktom Amanzadeh Oghaz ◽  
...  

Background: In human behavior study, by peering directly into the brain and assessing distinct patterns, evoked neurons and neuron spike can be more understandable by taking advantages of accurate brain analysis. Objectives: We investigated the role of Event Related Potentials (ERPs) in pre-comprehension processing of consumers to marketing logos.. Materials & Methods: In the framework of an experimental design, twenty-six right-handed volunteers (13 men, 13 women) participated in 2013 in the University of Tabriz. An individual task with a presentation of familiar vs. unfamiliar logos was designed. Stimuli were displayed on a monitor controlled by a PC using the Mitsar® stimulus presentation system PsyTask. Statistical analyses of ERPs data were analyzed by repeated measures ANOVA. Results: Our results showed, when subjects were dealing with familiar logos, higher peak amplitude for the N1 component in right hemisphere of the brain can be observed. These variations on averages of early components of ERPs in occipital lobe can be referred to the pre-perceptual brain activities. Conclusion: Investigating early components of ERP can be utilized further as an effective factor in prediction of the consumers ‘preference particularly in neuromarketing field.


Author(s):  
Tareef Sahal Daqqaq

Background This meta-analysis highlights the diagnostic efficacy of computed tomography (CT), computed tomography angiography (CTA), magnetic resonance image (MRI), as well as magnetic resonance spectroscopy (MRS). This paper assesses the detection of the primary outcome comprising choline/creatine (Cho/Cr) ratio, relative cerebral blood volume (rCBV), as well as choline/N-acetyl aspartate (Cho/NAA). Cochrane, Medline, ScienceDirect, Google Scholar, and EMBASE databases were searched for extracting the relevant studies. Methods A sample of 12 studies on radiological assessment of brain tumors was selected. Results The evidence provides that the heterogeneity exists concerning the CBV of 311.623, I2 = 96.12%, with a significance value of (p) &lt; 0.001. The pooled difference showed rCBV mean (as 2.18, 95%CI = 0.85 to 3.50) substantially enhances lesion. Conclusion The study concluded that radiological interventions, particularly the combination of MRS and MRI, help in the brain patient’s precise diagnosis and treatment.


2017 ◽  
Vol 114 (24) ◽  
pp. 6358-6363 ◽  
Author(s):  
Takashi Matsui ◽  
Hideki Omuro ◽  
Yu-Fan Liu ◽  
Mariko Soya ◽  
Takeru Shima ◽  
...  

Brain glycogen stored in astrocytes provides lactate as an energy source to neurons through monocarboxylate transporters (MCTs) to maintain neuronal functions such as hippocampus-regulated memory formation. Although prolonged exhaustive exercise decreases brain glycogen, the role of this decrease and lactate transport in the exercising brain remains less clear. Because muscle glycogen fuels exercising muscles, we hypothesized that astrocytic glycogen plays an energetic role in the prolonged-exercising brain to maintain endurance capacity through lactate transport. To test this hypothesis, we used a rat model of exhaustive exercise and capillary electrophoresis-mass spectrometry–based metabolomics to observe comprehensive energetics of the brain (cortex and hippocampus) and muscle (plantaris). At exhaustion, muscle glycogen was depleted but brain glycogen was only decreased. The levels of MCT2, which takes up lactate in neurons, increased in the brain, as did muscle MCTs. Metabolomics revealed that brain, but not muscle, ATP was maintained with lactate and other glycogenolytic/glycolytic sources. Intracerebroventricular injection of the glycogen phosphorylase inhibitor 1,4-dideoxy-1,4-imino-d-arabinitol did not affect peripheral glycemic conditions but suppressed brain lactate production and decreased hippocampal ATP levels at exhaustion. An MCT2 inhibitor, α-cyano-4-hydroxy-cinnamate, triggered a similar response that resulted in lower endurance capacity. These findings provide direct evidence for the energetic role of astrocytic glycogen-derived lactate in the exhaustive-exercising brain, implicating the significance of brain glycogen level in endurance capacity. Glycogen-maintained ATP in the brain is a possible defense mechanism for neurons in the exhausted brain.


2000 ◽  
Vol 20 (10) ◽  
pp. 1502-1507 ◽  
Author(s):  
Jullie W. Pan ◽  
Douglas L. Rothman ◽  
Kevin L. Behar ◽  
Daniel T. Stein ◽  
Hoby P. Hetherington

Ketones are known to constitute an important fraction of fuel for consumption by the brain, with brain ketone content generally thought to be low. However, the recent observation of 1-mmol/L levels of brain β-hydroxybutyrate (BHB) in children on the ketogenic diet suggests otherwise. The authors report the measurement of brain BHB and lactate in the occipital lobe of healthy adults using high field (4-T) magnetic resonance spectroscopy, measured in the nonfasted state and after 2-and 3-day fasting-induced ketosis. A 9-mL voxel located in the calcarine fissure was studied, detecting the BHB and lactate upfield resonances using a 1H homonuclear editing sequence. Plasma BHB levels also were measured. The mean brain BHB concentration increased from a nonfasted level of 0.05 ± 0.05 to 0.60 ± 0.26 mmol/L (after second day of fasting), increasing further to 0.98 ± 0.16 mmol/L (after the third day of fasting). The mean nonfasted brain lactate was 0.69 ± 0.17 mmol/L, increasing to 1.47 ± 0.22 mmol/L after the third day. The plasma and brain BHB levels correlated well ( r = 0.86) with a brain–plasma slope of 0.26. These data show that brain BHB rises significantly with 2-and 3-day fasting-induced ketosis. The lactate increase likely results from ketones displacing lactate oxidation without altering glucose phosphorylation and glycolysis.


Author(s):  
D Rajasree ◽  
T Lokesh Kumar ◽  
K Vijayalakshmi

Introduction: The ring enhancing lesions of the brain are a challenging group of lesions with the variable possibilities of diagnosis under conventional Magnetic Resonance Imaging (MRI). Employing advanced techniques such as Magnetic Resonance Spectroscopy (MRS) could increase the success rates of the diagnosis. Aim: To assess the role of MRS in evaluating varying ring enhancing lesions of the brain. Materials and Methods: This prospective observational study involved 50 patients aged between 3-82 years who were detected with ring enhancing lesions of the brain on contrast MR studies. The patients underwent MRS evaluation. Categorical data was represented as frequency (%). The metabolite peaks of choline, lipid, lactate, N-Acetyl Aspartate (NAA), succinate and amino acids were recorded. The choline/creatine ratio was calculated and associated with the type of lesion the patients exhibited. Results: Among the 50 patients screened, the most prevalent pathologies were tuberculoma (36%) and neurocysticercosis (22%). While the patients diagnosed with tuberculoma presented with higher peak level of lipids and choline/creatine ratio of >1-2. Increased lactate, succinate, choline peak concomitant with no or insignificant lipid peak, were noted in the cases of neurocysticercosis. Primary brain tumour showed high choline peaks and elevated choline/creatine ratio (>2). Metastasis showed increased choline peak. Cerebral abscess showed increased amino acids and lactate peak. Conclusion: The diagnosis of varying ring enhancing lesions of the brain was accurately investigated by MRS. This accuracy enables delineating a treatment plan void of any dilemma.


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