Glucose Injection Research Articles

The Potential of Glucose Treatment to Reduce Reactive Oxygen Species Production and Apoptosis of Inflamed Neural Cells In Vitro.

Neuroinflammation is a key feature in the pathogenesis of entrapment neuropathies. Clinical trial evidence suggests that perineural injection of glucose in water at entrapment sites has therapeutic benefits beyond a mere mechanical effect. We previously demonstrated that 12.5-25 mM glucose restored normal metabolism in human SH-SYFY neuronal cells rendered metabolically inactive from TNF-α exposure, a common initiator of neuroinflammation, and reduced secondary elevation of inflammatory cytokines. In the present study, we measured the effects of glucose treatment on cell survival, ROS activity, gene-related inflammation, and cell cycle regulation in the presence of neurogenic inflammation. We exposed SH-SY5Y cells to 10 ng/mL of TNF-α for 24 h to generate an inflammatory environment, followed by 24 h of exposure to 3.125, 6.25, 12.5, and 25 mM glucose. Glucose exposure, particularly at 12.5 mM, preserved apoptotic SH-SY5Y cell survival following a neuroinflammatory insult. ROS production was substantially reduced, suggesting a ROS scavenging effect. Glucose treatment significantly increased levels of CREB, JNK, and p70S6K (p < 0.01), pointing to antioxidative and anti-inflammatory actions through components of the MAPK family and Akt pathways but appeared underpowered (n = 6) to reach significance for NF-κB, p38, ERK1/2, Akt, and STAT5 (p < 0.05). Cell regulation analysis indicated that glucose treatment recovered/restored function in cells arrested in the S or G2/M-phases. In summary, glucose exposure in vitro restores function in apoptotic nerves after TNF-α exposure via several mechanisms, including ROS scavenging and enhancement of MAPK family and Akt pathways. These findings suggest that glucose injection about entrapped peripheral nerves may have several favorable biochemical actions that enhance neuronal cell function.

767-P: TERN-601, a Novel Oral GLP-1R Agonist, Suppresses Food Intake and Improves Glucose Tolerance in Transgenic Mice Expressing Human GLP-1 Receptor

Synthetic peptide agonists of the GLP-1 receptor (GLP-1R) are approved for the treatment of diabetes and obesity based on their ability to lower blood glucose and induce weight loss. TERN-601 is a novel, oral small molecule GLP-1R agonist in preclinical development. In vitro, TERN-601 potently stimulated (EC50 = 2.9 ± 0.8 nM) intracellular cAMP generation, a downstream consequence of GLP-1R activation, in CHO-K1 cells stably expressing human GLP-1R. In vivo, single oral doses of TERN-601 (10, 30, or 60 mg/kg) led to significant dose-dependent suppression of food intake (2- to 24-hours post dose) in transgenic C57BL/6J mice (n = 10 per group) expressing human GLP-1R (hGLP-1R). In an intraperitoneal glucose tolerance test (IPGTT) on overnight fasted hGLP-1R mice (n = 7 per group), single oral doses of TERN-601 (0.3, 1, and 3 mg/kg) administered 30 minutes prior to IP glucose injection significantly lowered blood glucose area under the curve (AUC0-120min) with comparable efficacy to liraglutide (0.3 mg/kg). TERN-601 is a potent, orally bioavailable small molecule agonist of human GLP-1R in preclinical development for the treatment of chronic obesity. In transgenic mice expressing human GLP-1R, single oral doses of TERN-601 significantly suppressed food intake and improved glucose tolerance. Together these data support the continued development of TERN-601. Disclosure C.Jones: Employee; Terns Pharmaceuticals. K.P.Quinn: None. C.H.Nelson: Employee; Terns Pharmaceuticals, Gilead Sciences, Inc., Stock/Shareholder; Terns Pharmaceuticals, Gilead Sciences, Inc. O.Osborn: Employee; Terns, Stock/Shareholder; ClicBio. G.Luehr: None. J.R.Jasper: Advisory Panel; Rubedo Life Sciences, Employee; Terns Pharmaceuticals, Rubedo Life Sciences.

Chronic alcohol-induced mesenteric lymphatic leakage is associated with local and systemic metabolic dysregulation

Introduction: Chronic alcohol administration produces significant metabolic dysfunction as determined in pre-clinical and clinical studies. Our studies using a rodent model of chronic alcohol feeding showed that alcohol induces mesenteric lymphatic leakage and perilymphatic adipose tissue (PLAT) immunometabolic dysregulation. Specifically, chronic alcohol induced localized PLAT inflammation and decreased glucose uptake. Whether chronic alcohol-induced lymphatic leakage is also associated with altered systemic glucose/insulin dynamics remained to be determined. We hypothesized that chronic alcohol feeding impairs the endocrine response to a glucose tolerance test. Methods: Male Fischer 344 rats were randomized to a Lieber-DeCarli liquid diet containing 36% of calories from alcohol or pair-fed an isocaloric diet for 10 weeks. Animals consumed approximately 75 mL of diet per day. Body weights were not significantly different between groups; the average weights were 275.7 grams for control animals and 275.9 grams for alcohol-fed animals. Weights in both groups remained stable for the duration of the study. At 10 weeks, animals were fasted for 16 hours prior to intraperitoneal (IP) injections of 20% glucose solution (2g/kg). Blood samples were collected from the rat tail prior to and at 15-minute intervals following initial glucose injection for 2 hours. Blood glucose was tested at each interval using the AlphaTRAK glucometer. 2-way ANOVA and paired T-test were used to assess significant differences between groups. Results and Conclusion: Prior to IP glucose injection, blood glucose levels averaged 77 mg/dL for control animals and 71.5 mg/dL for alcohol-fed animals. Glucose levels in alcohol-fed animals averaged 38% higher at 15 minutes and 37% higher 30 minutes after IP glucose bolus than that of control animals. Total area under the curve (AUC) calculated from the glucose concentrations measured following IP glucose injection was significantly higher in alcohol-fed animals compared to control animals; average AUC for alcohol-fed animals was 26.8% higher than AUC for control animals. These results suggest that chronic alcohol-induced mesenteric lymphatic leakage and localized PLAT inflammation and altered glucose metabolism are also associated with disturbances in systemic glucose dysregulation. Future studies will examine the potential link between alcohol-induced PLAT immunometabolic dysregulation and alterations in systemic glucose metabolism. Supported by T32 (PM), K01 (FS). This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Investigations into the Signaling Pathways Involving Glucose-Stimulated Zinc Secretion (GSZS) from Prostate Epithelial Cells In Vitro and In Vivo.

Recently, we reported that exposure of prostate cells in vitro or the in vivo prostate to high glucose results in release of Zn2+ ions, a process now referred to as glucose-stimulated zinc secretion (GSZS). To our knowledge, the metabolic event(s) that trigger GSZS remain largely unknown. Here, we explore several signaling pathways both in vitro using a prostate epithelial cell line and in vivo from the rat prostate. PNT1A cells grown to confluence were washed and tagged with ZIMIR to monitor zinc secretion by optical methods. The expression levels of GLUT1, GLUT4, and Akt in cells cultured in either zinc-rich or zinc-poor media and after exposure to high versus low glucose were determined. Zinc secretion from the rat prostate in vivo as detected by MRI was compared in control animals after injection of glucose, deoxyglucose, or pyruvate to initiate zinc secretion and in animals pre-treated with WZB-117 (a GLUT1 inhibitor) or S961 (a peripheral insulin receptor inhibitor). PNT1A cells exposed to high levels of glucose secrete zinc whereas cells exposed to an equivalent amount of deoxyglucose or pyruvate do not. Expression of Akt was dramatically altered by zinc supplementation of the culture media but not after exposure to glucose while GLUT1 and GLUT4 levels were less affected. Rats pre-treated with WZB-117 prior to imaging showed a reduction in GSZS from the prostate compared to controls whereas rats pre-treated with S961 showed no difference. Interestingly, in comparison to PNT1A cells, pyruvate and deoxyglucose also stimulate zinc secretion in vivo likely through indirect mechanisms. GSZS requires metabolism of glucose both in vitro (PNT1A cells) and in vivo (rat prostate). Pyruvate also stimulates zinc secretion in vivo but likely via an indirect pathway involving rapid production of glucose via gluconeogenesis. These combined results support the conclusion that glycolytic flux is required to trigger GSZS in vivo.

In vivo photoacoustic monitoring of vasoconstriction induced by acute hyperglycemia

Postprandial hyperglycemia, blood glucose spikes, induces endothelial dysfunction, increasing cardiovascular risks. Endothelial dysfunction leads to vasoconstriction, and observation of this phenomenon is important for understanding acute hyperglycemia. However, high-resolution imaging of microvessels during acute hyperglycemia has not been fully developed. Here, we demonstrate that photoacoustic microscopy can noninvasively monitor morphological changes in blood vessels of live animals’ extremities when blood glucose rises rapidly. As blood glucose level rose from 100 to 400 mg/dL following intraperitoneal glucose injection, heart/breath rate, and body temperature remained constant, but arterioles constricted by approximately –5.7 ± 1.1% within 20 min, and gradually recovered for another 40 min. In contrast, venular diameters remained within about 0.6 ± 1.5% during arteriolar constriction. Our results experimentally and statistically demonstrate that acute hyperglycemia produces transitory vasoconstriction in arterioles, with an opposite trend of change in blood glucose. These findings could help understanding vascular glucose homeostasis and the relationship between diabetes and cardiovascular diseases.

Direct Electrochemistry of Glucose Dehydrogenase-Functionalized Polymers on a Modified Glassy Carbon Electrode and Its Molecular Recognition of Glucose.

A glucose biosensor was layer-by-layer assembled on a modified glassy carbon electrode (GCE) from a nanocomposite of NAD(P)+-dependent glucose dehydrogenase, aminated polyethylene glycol (mPEG), carboxylic acid-functionalized multi-wall carbon nanotubes (fMWCNTs), and ionic liquid (IL) composite functional polymers. The electrochemical electrode was denoted as NF/IL/GDH/mPEG-fMWCNTs/GCE. The composite polymer membranes were characterized by cyclic voltammetry, ultraviolet-visible spectrophotometry, electrochemical impedance spectroscopy, scanning electron microscopy, and transmission electron microscopy. The cyclic voltammogram of the modified electrode had a pair of well-defined quasi-reversible redox peaks with a formal potential of -61 mV (vs. Ag/AgCl) at a scan rate of 0.05 V s-1. The heterogeneous electron transfer constant (ks) of GDH on the composite functional polymer-modified GCE was 6.5 s-1. The biosensor could sensitively recognize and detect glucose linearly from 0.8 to 100 µM with a detection limit down to 0.46 μM (S/N = 3) and a sensitivity of 29.1 nA μM-1. The apparent Michaelis-Menten constant (Kmapp) of the modified electrode was 0.21 mM. The constructed electrochemical sensor was compared with the high-performance liquid chromatography method for the determination of glucose in commercially available glucose injections. The results demonstrated that the sensor was highly accurate and could be used for the rapid and quantitative determination of glucose concentration.

A Microelectrode Array Modified by PtNPs/PB Nanocomposites Used for the Detection and Analysis of Glucose-Sensitive Neurons under Different Blood Glucose States.

Hypoglycemia state damages the organism, and glucose-excited and glucose-inhibited neurons from the ventral medial hypothalamus can regulate this state. Therefore, it is crucial to understand the functional mechanism between blood glucose and electrophysiology of glucose-excited and glucose-inhibited neurons. To better detect and analyze this mechanism, a PtNPs/PB nanomaterials modified 32-channel microelectrode array with low impedance (21.91 ± 6.80 kΩ), slight phase delay (-12.7° ± 2.7°), high double layer capacitance (0.606 μF), and biocompatibility was developed to realize in vivo real-time detection of the electrophysiology activities of glucose-excited and glucose-inhibited neurons. The phase-locking level of some glucose-inhibited neurons elevated during fasting (low blood glucose state) and showed theta rhythms after glucose injection (high blood glucose state). With an independent oscillating ability, glucose-inhibited neurons can provide an essential indicator to prevent severe hypoglycemia. The results reveal a mechanism for glucose-sensitive neurons to respond to blood glucose. Some glucose-inhibited neurons can integrate glucose information input and convert it into theta oscillating or phase lock output. It helps in enhancing the interaction between neurons and glucose. Therefore, the research can provide a basis for further controlling blood glucose by modulating the characteristics of neuronal electrophysiology. This helps reduce the damage of organisms under energy-limiting conditions, such as prolonged manned spaceflight or metabolic disorders.

Molecular identification of an insulin-like peptide from the swimming crab Portunus trituberculatus and evidence for its glucoregulation function

Insulin-like peptides (ILPs) are essential to the animal kingdom for regulating growth and development, reproduction, behavior, metabolism, and lifespan. In crustaceans, the most well-known ILP is insulin-like androgenic gland hormone, a key hormone in regulating sex differentiation and reproduction. Identification of other ILPs and their functions are still limited. In this study, an insulin-like peptide gene of the swimming crab Portunus trituberculatus was cloned and characterized. Its transcripts were mainly found in nerve tissues and expression could be induced by glucose, implying a putative role in glucoregulation. After depletion of endogenous ILP, injection of ILP dsRNA (dsILP) significantly elevated blood glucose levels and recombinant ILP (rILP) decreased hemolymph glucose levels, further clarifying the involvement of acquired ILP in hemolymph glucose regulation. Injection of dsILP decreased PtAkt, PtGS, PtPFK and increased PtGSK and PtPEPCK gene expression. The opposite profile was observed after glucose and rILP injection, indicating that PtILP might negatively regulate hemolymph glucose levels via the IIS (insulin/IGF-1 signaling) pathway by inhibiting gluconeogenesis and promoting glycogen synthesis and glycolysis. This study has refined the mechanism of glucose regulation in crustaceans and laid the foundation for further studies on ILP function.

Rationale and design of the RESTORE trial: A multicenter, randomized, double-blinded, parallel-group, placebo-controlled trial to evaluate the effect of Shenfu injection on myocardial injury in STEMI patients after primary PCI

BackgroundThe mortality following ST-segment elevation myocardial infarction (STEMI) remains substantial in the reperfusion era. Shenfu injection, as a traditional Chinese herbal formula, can alleviate ischemia-reperfusion injury through multiple pharmacologic effects. However, no robust data are available regarding the role of Shenfu injection in reducing infarct size for patients with STEMI undergoing primary percutaneous coronary intervention (PPCI). Methods/DesignThis RESTORE trial is a multicenter, randomized, double-blind, parallel-group, placebo-controlled trial (NCT04493840). A total of 326 eligible patients with first-time anterior STEMI undergoing PPCI within 12 h of symptom onset will be enrolled from 10 centers in mainland China. Patients are randomized in a 1:1 fashion to receive either intravenous Shenfu injection (80mL Shenfu injection + 70mL 5% glucose injection) or placebo group (150mL 5% glucose injection) before reperfusion and followed by once a day until 5 days after PPCI. The primary end point is infarct size assessed by cardiac magnetic resonance (CMR) imaging 5±2 days after PPCI. The major secondary end points include enzymatic infarct size, microvascular obstruction, intramyocardial hemorrhage, left ventricular volume and ejection fraction assessed by CMR, as well as cardiovascular events at 30 days. ConclusionsThe RESTORE trial is sufficiently powered to demonstrate the clinical effects of Shenfu injection on myocardial injury in STEMI patients undergoing PPCI in the contemporary era.

Chronic cortisol elevation restricts glucose uptake but not insulin responsiveness in zebrafish skeletal muscle

Although teleosts show an elevated insulin response to hyperglycemia, the circulating glucose levels are not normalized as rapidly as in mammals. While this may suggest a lack of target tissue insulin responsiveness, the underlying mechanisms are unclear. We investigated whether changes in skeletal muscle insulin sensitivity and glucose uptake underlie the cortisol-mediated elevated blood glucose levels. Adult zebrafish (Danio rerio) were exposed to water-borne cortisol for 3 days followed by an intraperitoneal injection of glucose with or without insulin. Cortisol treatment resulted in a temporal delay in the reduction in blood glucose levels, and this corresponded with a reduced glucose uptake capacity and lower glycogen content in the skeletal muscle. The transcript abundance of slc2a1b (which encodes for GLUT1b) and a suite of genes encoding enzymes involved in muscle glycogenesis and glycolysis were upregulated in the cortisol group. Both the control and cortisol groups showed higher whole body insulin expression in response to blood glucose elevation, which also resulted in enhanced insulin-stimulated phosphorylation of AKT in the skeletal muscle. The insulin-mediated phosphorylation of S6 kinase was lower in the cortisol group. Altogether, chronic cortisol stimulation restricts glucose uptake and enhances the glycolytic capacity without affecting insulin responsiveness in zebrafish skeletal muscle.

Abstract WP225: Rapid Complement Activation Induced By Acute Hyperglycemia Worsens Ischemic Stroke Outcome

Background: Acute hyperglycemia, which occurs in over 40% of ischemic stroke patients regardless of pre-existing diabetes, increases brain edema, hemorrhagic transformation (HT) and worsens stroke outcome. Understanding the mechanisms of hyperglycemia-exacerbated stroke injury will be vital for developing novel treatments. Here we identify systemic complement activation as a novel contributor to hyperglycemic-exacerbated damage in rodent stroke. Method: Male C57/BL6 mice (10-11 weeks) were subjected to middle cerebral artery occlusion (MCAO) for 30 min, followed by reperfusion to mimic ischemic stroke. Acute hyperglycemia was induced by glucose injection 10 min before MCAO. To assess the effect of hyperglycemia on stroke outcomes, mice were sacrificed at 4.5 and 24 hr post-stroke to analyze brain edema, blood-brain barrier (BBB) leakage, and HT; or allowed to survive 14 days to examine mortality rate, neurological deficit, and motor-sensory dysfunction using the horizontal rotating beam test. Complement activation was evaluated at 1, 2, 4.5 hr post-stroke. To inhibit C3 activation, the targeted complement inhibitor CR2-Crry fusion protein, or PBS control, was injected via femoral vein 15 min after reperfusion. Result: Hyperglycemia worsens stroke outcomes in our mouse model, with rapid increased BBB leakage (p&lt;0.0001), brain swelling (p&lt;0.001) and HT at (p&lt;0.0001) 4.5 and 24 hr after stroke compared to normoglycemia; and poorer prognosis including higher mortality (100% VS 25%, p=0.0008), body weight loss, and impaired behavioral performance by day 14. Interestingly, acute hyperglycemia rapidly increased plasma complement C3 levels at 1 and 2 hr after stroke (p&lt;0.01 compared to normoglycemic mice), accompanied by activation of C3 in ischemic brain vessels as indicated by elevated levels of vascular C3d. Vascular C3d colocalized with IgM/IgG, suggesting the involvement of classical pathway in C3 activation. Notably, activated C3 levels positively correlated with brain swelling and HT (p&lt;0.01). Inhibition of C3 by CR2-Crry markedly reduced brain swelling (p&lt;0.05) and HT in hyperglycemic stroke. Conclusion: Rapid activation of complement C3 by acute hyperglycemia may be an important contributor to BBB leakage, brain swelling and HT.

Improvement Automatic Diabetic Management System using Fuzzy Logic

In almost every nation on the planet, diabetes may be a common chronic condition. Monitoring blood glucose levels is essential to preventing diabetic complications and organ damage. The most used technique for monitoring blood glucose levels is intrusive, uncomfortable, expensive, and risky for transmitting infectious infections. The invasive procedure harms the tissues in the fingers over time. The suggested system functions on a diabetic patient and informs the caregiver or observer of the patient's state. The patient's fingertip is inserted between the glucose-measuring sensors, which a microcontroller uses to calculate the patient's glucose level. When the body's glucose level rises, an insulin injector will automatically inject insulin; glucose will be injected when it falls. The patient's mobile application is utilized to view the insulin and glucose injection amounts and the glucose measurements taken each time. When in critical condition, an SMS is sent to the doctor's or a family member's phone with crucial information and the patient's location.

Deletion of Tbc1d4/As160 abrogates cardiac glucose uptake and increases myocardial damage after ischemia/reperfusion

BackgroundType 2 Diabetes mellitus (T2DM) is a major risk factor for cardiovascular disease and associated with poor outcome after myocardial infarction (MI). In T2DM, cardiac metabolic flexibility, i.e. the switch between carbohydrates and lipids as energy source, is disturbed. The RabGTPase-activating protein TBC1D4 represents a crucial regulator of insulin-stimulated glucose uptake in skeletal muscle by controlling glucose transporter GLUT4 translocation. A human loss-of-function mutation in TBC1D4 is associated with impaired glycemic control and elevated T2DM risk. The study’s aim was to investigate TBC1D4 function in cardiac substrate metabolism and adaptation to MI.MethodsCardiac glucose metabolism of male Tbc1d4-deficient (D4KO) and wild type (WT) mice was characterized using in vivo [18F]-FDG PET imaging after glucose injection and ex vivo basal/insulin-stimulated [3H]-2-deoxyglucose uptake in left ventricular (LV) papillary muscle. Mice were subjected to cardiac ischemia/reperfusion (I/R). Heart structure and function were analyzed until 3 weeks post-MI using echocardiography, morphometric and ultrastructural analysis of heart sections, complemented by whole heart transcriptome and protein measurements.ResultsTbc1d4-knockout abolished insulin-stimulated glucose uptake in ex vivo LV papillary muscle and in vivo cardiac glucose uptake after glucose injection, accompanied by a marked reduction of GLUT4. Basal cardiac glucose uptake and GLUT1 abundance were not changed compared to WT controls. D4KO mice showed mild impairments in glycemia but normal cardiac function. However, after I/R D4KO mice showed progressively increased LV endsystolic volume and substantially increased infarction area compared to WT controls. Cardiac transcriptome analysis revealed upregulation of the unfolded protein response via ATF4/eIF2α in D4KO mice at baseline. Transmission electron microscopy revealed largely increased extracellular matrix (ECM) area, in line with decreased cardiac expression of matrix metalloproteinases of D4KO mice.ConclusionsTBC1D4 is essential for insulin-stimulated cardiac glucose uptake and metabolic flexibility. Tbc1d4-deficiency results in elevated cardiac endoplasmic reticulum (ER)-stress response, increased deposition of ECM and aggravated cardiac damage following MI. Hence, impaired TBC1D4 signaling contributes to poor outcome after MI.

Building the conformal protection of VB-group VS2 laminated heterostructure based on biomass-derived carbon for excellent broadband electromagnetic waves absorption

Although VB-Group transition metal disulfides (TMDs) VS2 nanomaterials with specific electronic properties and multiphase microstructures have shown fascinating potential in the field of electromagnetic wave (EMW) absorption, the efficient utilization of VS2 is limited by the technical bottleneck of its narrow effective absorption bandwidth (EAB) which is attributed to environmental instability and a deficient electromagnetic (EM) loss mechanism. In order to fully exploit the maximal utilization values of VS2 nanomaterials for EMW absorption through mitigating the chemical instability and optimizing the EM parameters, biomass-based glucose derived carbon (GDC) like sugar-coating has been decorated on the surface of stacked VS2 nanosheets via a facile hydrothermal method, followed by high-temperature carbonization. As a result, the modulation of doping amount of glucose injection solution (Glucose) could effectively manipulate the encapsulation degree of GDC coating on VS2 nanosheets, further implementing the EM response mechanisms of the VS2/GDC hybrids (coupling effect of conductive loss, interfacial polarization, relaxation, dipole polarization, defect engineering and multiple reflections and absorptions) through regulating the conductivity and constructing multi-interface heterostructures, as reflected by the enhanced EMW absorption performance to a great extent. The minimum reflection loss (Rmin) of VS2/GDC hybrids could reach −52.8 dB with a thickness of 2.7 mm at 12.2 GHz. Surprisingly, compared with pristine VS2, the EAB of the VS2/GDC hybrids increased from 2.0 to 5.7 GHz, while their environmental stability was effectively enhanced by virtue of GDC doping. Obviously, this work provides a promising candidate to realize frequency band tunability of EMW absorbers with exceptional performance and environmental stability.

Changes of Hemodynamic Parameters after Intradialytic Glucose Injection.

Intradialytic hypotension (IDH) is a frequent complication of hemodialysis (HD). Current methods of IDH prevention are insufficient. We analyzed the intradialytic time course of systolic (SBP), diastolic (DBP), mean arterial (MAP), pulse pressure (PP), and heart rate (HR) in a group of chronic kidney disease (CKD) patients. First, 30 min into HD, a 40% glucose solution was injected into the venous line of the extracorporeal circulation at a dose of 0.5 g/kg of dry weight. Pressures and HR were measured in frequent intervals. Relative volume overload was determined by bioimpedance spectroscopy. Thirty-five participants were studied. SBP increased after 5, 10, and 20 min of glucose infusion. DBP increased after 2 and 3 h and also at the end of HD. PP increased after 5, 10, and 20 min of glucose infusion and fell after the 2nd and 3rd hour and also at the end of HD. MAP increased after 2 and 3 h of glucose injection and at the end of HD. Significant interactions of the time course of SBP, DBP, MAP, with HR at baseline and of the time course of PP with fluid overload were observed. Symptomatic hypotensive episodes were absent. Glucose infusions during HD prevent symptomatic IDH and do not cause severe hypertensive episodes.

Environmental enrichment accentuates glucose-induced feeding suppression and glial cell line-derived neurotrophic factor gene expression in the hypothalamus of mice

ABSTRACT The hypothalamus controls food intake by integrating nutrient signals, of which one of the most important is glucose. Consequently, impairments in hypothalamic glucose-sensing mechanisms are associated with hyperphagia and obesity. Environmental enrichment (EE) is an animal housing protocol that provides complex sensory, motor, and social stimulations and has been proven to reduce adiposity in laboratory mice. However, the mechanism by which EE promotes adiposity-suppressing effect remains incompletely understood. Neurotrophic factors play an important role in the development and maintenance of the nervous system, but they are also involved in the hypothalamic regulation of feeding. Brain-derived neurotrophic factor (BDNF) and glial cell line-derived neurotrophic factor (GDNF) are expressed in the hypothalamus and their expression is stimulated by glucose. EE is associated with increased expression of Bdnf mRNA in the hypothalamus. Therefore, we hypothesized that EE potentiates the anorectic action of glucose by altering the expression of neurotrophic factor genes in the hypothalamus. Male C57BL/6 mice were maintained under standard or EE conditions to investigate the feeding response to glucose and the associated expression of feeding-related neurotrophic factor genes in the hypothalamus. Intraperitoneal glucose injection reduced food intake in both control and EE mice with a significantly greater reduction in the EE group compared to the control group. EE caused a significantly enhanced response of Gdnf mRNA expression to glucose without altering basal Gdnf mRNA expression and Bdnf mRNA response to glucose. These findings suggest that EE enhances glucose-induced feeding suppression, at least partly, by enhancing hypothalamic glucose-sensing ability that involves GDNF.

Shenxiong glucose injection inhibits oxidative stress and apoptosis to ameliorate isoproterenol-induced myocardial ischemia in rats and improve the function of HUVECs exposed to CoCl2.

Background: Shenxiong Glucose Injection (SGI) is a traditional Chinese medicine formula composed of ligustrazine hydrochloride and Danshen (Radix et rhizoma Salviae miltiorrhizae; Salvia miltiorrhiza Bunge, Lamiaceae). Our previous studies and others have shown that SGI has excellent therapeutic effects on myocardial ischemia (MI). However, the potential mechanisms of action have yet to be elucidated. This study aimed to explore the molecular mechanism of SGI in MI treatment. Methods: Sprague-Dawley rats were treated with isoproterenol (ISO) to establish the MI model. Electrocardiograms, hemodynamic parameters, echocardiograms, reactive oxygen species (ROS) levels, and serum concentrations of cardiac troponin I (cTnI) and cardiac troponin T (cTnT) were analyzed to explore the protective effect of SGI on MI. In addition, a model of oxidative damage and apoptosis in human umbilical vein endothelial cells (HUVECs) was established using CoCl2. Cell viability, Ca2+ concentration, mitochondrial membrane potential (MMP), apoptosis, intracellular ROS, and cell cycle parameters were detected in the HUVEC model. The expression of apoptosis-related proteins (Bcl-2, Caspase-3, PARP, cytoplasmic and mitochondrial Cyt-c and Bax, and p-ERK1/2) was determined by western blotting, and the expression of cleaved caspase-3 was analyzed by immunofluorescence. Results: SGI significantly reduced ROS production and serum concentrations of cTnI and cTnT, reversed ST-segment elevation, and attenuated the deterioration of left ventricular function in ISO-induced MI rats. In vitro, SGI treatment significantly inhibited intracellular ROS overexpression, Ca2+ influx, MMP disruption, and G2/M arrest in the cell cycle. Additionally, SGI treatment markedly upregulated the expression of anti-apoptotic protein Bcl-2 and downregulated the expression of pro-apoptotic proteins p-ERK1/2, mitochondrial Bax, cytoplasmic Cyt-c, cleaved caspase-3, and PARP. Conclusion: SGI could improve MI by inhibiting the oxidative stress and apoptosis signaling pathways. These findings provide evidence to explain the pharmacological action and underlying molecular mechanisms of SGI in the treatment of MI.

"Revolutionizing Amyotrophic Lateral Sclerosis (ALS) Management: A Case Report on Muscle Regeneration and Sustained Relaxation through Placental Injection Therapy at Rodem Hospital"

This case report from the Rodem Hospital introduces a pioneering intervention for muscle rigidity in Amyotrophic Lateral Sclerosis (ALS), featuring a unique placental extract injection and glucose injection therapy combined with lidocaine. This novel approach has demonstrated significant muscle regeneration and sustained relaxation in 47 ALS patients. Unlike traditional treatments, this protocol offers a more sustainable and regenerative outcome. The treatment involved injections of a mixture containing glucose, lidocaine, and placental extract, targeting severely rigid muscles. Remarkably, 42 of the 47 patients showed considerable improvements in knee flexion and a dramatic reduction in pain. The other two also experienced notable progress. This method stands out for its cost efficiency, impact on muscle suppleness, and reduced pain, suggesting a potential paradigm shift in ALS management. This case series highlights the importance of continued innovation and personalized treatment strategies in ALS care, aiming to improve patient quality of life and functional abilities. This case report from the Rodem Hospital introduces a pioneering intervention for muscle rigidity in Amyotrophic Lateral Sclerosis (ALS), featuring a unique placental extract injection and glucose injection therapy combined with lidocaine. This novel approach has demonstrated significant muscle regeneration and sustained relaxation in 47 ALS patients. Unlike traditional treatments, this protocol offers a more sustainable and regenerative outcome. The treatment involved injections of a mixture containing glucose, lidocaine, and placental extract, targeting severely rigid muscles. Remarkably, 42 of the 47 patients showed considerable improvements in knee flexion and a dramatic reduction in pain. The other two also experienced notable progress. This method stands out for its cost efficiency, impact on muscle suppleness, and reduced pain, suggesting a potential paradigm shift in ALS management. This case series highlights the importance of continued innovation and personalized treatment strategies in ALS care, aiming to improve patient quality of life and functional abilities.

Cardiovascular Response to Intravenous Glucose Injection during Hemodialysis with Assessment of Entropy Alterations.

The quality of autonomic blood pressure (BP) control can be assessed by the entropy of serial BP data. The aim of this study was to evaluate the effect of hemodialysis (HD) and glucose infusion (GI) on amplitude aware permutation entropy (AAPE) of hemodynamic variables during HD in chronic kidney disease patients with and without type-2 diabetes mellitus (DM). Twenty-one patients without DM (NDO) and ten with DM were studied. Thirty minutes after the start of HD, a 40% glucose solution was administered. Hemodynamic data were extracted from continuous recordings using the Portapres® system. AAPE decreased during HD in all patients and all hemodynamic signals with the exception of AAPE of mean and diastolic BP in DM patients. GI led to an increase in AAPE for cardiac output in all patients, while AAPE for heart rate and ejection time increased only in DM studies, and AAPE for systolic, diastolic, and mean arterial pressure, as well as total peripheral resistance, increased only in NDO patients. The reduction in entropy during HD indicates impaired autonomic control in response to external perturbations. This state is partially reversed by the infusion of glucose with differences in central and peripheral responsiveness in DM and NDO patients.

A crucial role in osmoregulation against hyperosmotic stress: Carbohydrate and inositol metabolism in Nile tilapia (Oreochromis niloticus)

The purpose of this study was to explore the relationship between inositol metabolism and carbohydrate metabolism in Nile tilapia (Oreochromis niloticus) under acute hyperosmotic stress. 50 mg/mL glucose solution and PBS was injected to the fish of experimental group and the control group, respectively. The fish were then transferred to 16 psu brackish water for hyperosmotic stress immediately, and sampled at 0, 1, 3, 6, 12, 24, and 48 h post stress. The hyperosmotic stress significantly increased the osmotic pressure, glucose content of serum, the process of glycolysis and gluconeogenesis in the liver of fish in both groups over time. The expression of genes involved in myo-inositol (MI) synthesis and transport was all induced by hypertonicity in gill, kidney and liver of fish in both groups. The injection of glucose solution significantly decreased MI synthesis in gill, kidney and liver, and relieved the apoptosis of liver under acute hyperosmotic stress. However, glucose injection significantly increased Na+K+-ATPase activity in the gill, as well as serum osmotic pressure, and the decomposition of carbohydrate, indicating that additional glucose promoted osmoregulation ability of fish. The results of this research suggested that during the hyperosmotic stress, the injection of exogenous glucose could not only provide energy that required for osmoregulation, but also participate in the osmoregulation by acting as an osmolyte itself.