Low Glucose Concentrations Research Articles

Glucagon in health and diabetes

Abstract For decades all attention focused on the hormone insulin as a key player in diabetes and the role of glucagon was less studied or understood. We now know that both these pancreatic hormones play a critical role in maintaining glucose homeostasis in the body and the secretion of one controls the secretion of the other in an inverse relationship as described by the bihormonal theory of Unger. Glucagon, secreted by the α-cells of the islets of pancreas is a key hormone that has a “hyperglycemic” effect and is secreted in response to low plasma glucose concentration. Besides hypoglycemia, glucagon release is also stimulated by prolonged fasting or starvation, exercise as well as consumption of protein-rich meals. It is regulated by several key endocrine and paracrine mechanisms and the autonomic system in response to various stimuli including nutrient intake through various complex neurohormonal factors. It primarily increases endogenous hepatic glucose production, stimulates lipid and protein catabolism, and plays a key role in appetite regulation and increasing energy expenditure. Therefore, glucagon functions as a counter-regulatory hormone to insulin stimulating hepatic glycogenolysis, gluconeogenesis, fatty acid oxidation, and ketogenesis. With mounting evidence, there has been a paradigm shift in the management of diabetes following the advent of new agents that address different pathophysiological mechanisms contributing to worsening hyperglycemia. Targeting the alpha-cell defect and consequent glucagon hypersecretion has therefore emerged as an important therapeutic strategy in type 2 diabetes mellitus (T2DM) management as well as body weight management. The currently available medications, including glucagon-like peptide 1 (GLP-1) receptor agonists, DPP-4 inhibitors, and amylin mimics (pramlintide), essentially focus on lowering glucagon levels and correcting this critical pathophysiological component in the multifactorial T2DM management strategies.

The SGLT2 inhibitor dapagliflozin improves kidney function in glycogen storage disease XI.

Glycogen storage disease XI, also known as Fanconi-Bickel syndrome (FBS), is a rare autosomal recessive disorder caused by mutations in the SLC2A2 gene that encodes the glucose-facilitated transporter type 2 (GLUT2). Patients develop a life-threatening renal proximal tubule dysfunction for which no treatment is available apart from electrolyte replacement. To investigate the renal pathogenesis of FBS, SLC2A2 expression was ablated in mouse kidney and HK-2 proximal tubule cells. GLUT2Pax8Cre+ mice developed time-dependent glycogen accumulation in proximal tubule cells and recapitulated the renal Fanconi phenotype seen in patients. In vitro suppression of GLUT2 impaired lysosomal autophagy as shown by transcriptomic and biochemical analysis. However, this effect was reversed by exposure to a low glucose concentration, suggesting that GLUT2 facilitates the homeostasis of key cellular pathways in proximal tubule cells by preventing glucose toxicity. To investigate whether targeting proximal tubule glucose influx can limit glycogen accumulation and correct symptoms in vivo, we treated mice with the selective SGLT2 inhibitor dapagliflozin. Dapagliflozin reduced glycogen accumulation and improved metabolic acidosis and phosphaturia in the animals by normalizing the expression of Napi2a and NHE3 transporters. In addition, in a patient with FBS, dapagliflozin was safe, improved serum potassium and phosphate concentrations, and reduced glycogen content in urinary shed cells. Overall, this study provides proof of concept for dapagliflozin as a potentially suitable therapy for FBS.

Homeostasis Model Assessment of β-Cell Function for Diagnosis of Insulinoma.

Diagnosis of insulinoma is based on different criteria from the 72-hour fasting test according to current guidelines (Endocrine Society [ES], European [ENETS], and North American [NANETS] Neuroendocrine Tumor Societies), including assessment of β-cell function by glucagon stimulation test. This study tested whether the homeostasis model assessment of insulin secretion, including assessment of β-cell function, (HOMA-B) at the end of the fasting test provides comparable efficacy for insulinoma diagnosis. In 104 patients with suspected insulinoma, 72-hour fasting tests were performed with frequent assessment of glucose, insulin, and C-peptide in venous blood. HOMA-B values using insulin and C-peptide were calculated at the end of the fasting test, as defined by the lowest glucose concentration from each participant. HOMA-B was more than 6.5-fold higher in patients with (n = 23) than in those without (n = 81) insulinoma (insulin and C-peptide; both P < .001). HOMA-B (cutoff using insulin >253 a.u. and C-peptide >270 a.u.) had a sensitivity of 0.96, 0.78 to 1.00, and a specificity of 0.96 or greater (≥0.89-0.99) for insulinoma diagnosis. ES and ENETS/NANETS criteria reached a diagnostic sensitivity of less than or equal to 0.96 (≤0.78-1.00) and ≤0.83 (≤0.61-0.95) as well as specificity of ≤0.85 (≤0.76-0.92) and less than or equal to 1.00 (≤0.96-1.00) for insulin, and C-peptide, respectively. Using insulin for HOMA-B, sensitivity tended to be higher compared to ENETS/NANETS criteria (P = .063) and specificity was higher compared to ES criteria using insulin and C-peptide (both P < .005). HOMA-B, as calculated at the end of the fasting test employing defined cutoffs for insulin and C-peptide, provides excellent diagnostic efficacy, suggesting that it might represent an alternative and precise tool to diagnose insulinoma.

Betaine regulates steroidogenesis, endoplasmic reticulum stress response and Nrf2/HO-1 antioxidant pathways in mouse Leydig cells under hyperglycaemia condition

We studied the effects of betaine on steroidogenesis, endoplasmic reticulum stress and Nrf2 antioxidant pathways of mice Leydig cells under hyperglycaemia conditions. Leydig cells were grown in low and high glucose concentrations (5 mM and 30 mM) in the presence of 5 mM of betaine for 24 h. Gene expression was determined using a real-time PCR method. The protein levels were determined by Western blot analysis. The testosterone production was evaluated by the ELISA method. Cellular contents of reduced and oxidised glutathione were measured by colorimetric method. Hyperglycaemia caused impaired steroidogenesis and ERS in Leydig cells associated with the down-regulation of 3β-HSD, StAR, P450scc, LH receptor and increased expression of GRP78, CHOP, ATF6 and IRE1. Betaine could improve cell viability, attenuate the ERS, and restore testosterone production in Leydig cells under hyperglycaemia conditions. Betaine can protect Leydig cells against the adverse effects of hyperglycaemia by regulating steroidogenesis, antioxidants, and ERS.

Chromium propionate in turkeys: effects on insulin sensitivity

The objective of this study was to evaluate the effects of dietary chromium (Cr), as Cr propionate (Cr Prop), on measures of insulin sensitivity in turkeys. Plasma glucose and nonesterified fatty acid (NEFA), and liver glycogen concentrations were used as indicators of insulin sensitivity. One-day-old Nicholas Large White female poults (n=336) were randomly assigned to dietary treatments consisting of 0 (control), 0.2, 0.4, or 0.6 mg supplemental Cr/kg diet. Each treatment consisted of 12 replicate cages with 7 turkeys per cage. Final BW were taken on d 34, and on d 35 two birds from each cage were sampled for plasma glucose and NEFA, and liver glycogen determination at the initiation (fed state) and termination (fasted state) of a 24-h fast. Following a 24-h fast, 2 turkeys per cage were refed (refed state) their treatment diet for 4 h, and then harvested. Feed/gain and ADG did not differ between control and Cr-supplemented turkeys over the 34-d study, but feed intake tended (P=0.071) to be greater for controls than turkeys receiving 0.4 mg Cr/kg diet. Fed turkeys had greater plasma glucose (P=0.002) and liver glycogen (P=0.001) concentrations, and lower (P=0.001) NEFA concentrations than fasted birds. Turkeys refed after fasting had greater (P=0.001) plasma glucose and liver glycogen concentrations, and lower (P=0.001) plasma NEFA levels than fed turkeys. Liver glycogen and plasma NEFA concentrations did not differ among control and Cr-supplemented birds in the fed, fasted, or refed state. Plasma glucose concentrations were not affected by treatment in fed or fasted turkeys. Turkeys supplemented with 0.2 or 0.4 mg Cr/kg and refed after fasting had lower (quadratic, P=0.038) plasma glucose concentrations than controls. Plasma glucose concentrations in refed birds did not differ among Cr-supplemented turkeys. The lower plasma glucose concentration in Cr-supplemented turkeys following refeeding is consistent with Cr enhancing insulin sensitivity.

Carbon Microspheres with Cr(VI) Adsorption Performance were Prepared by In-situ Hydrothermal Carbonization Method

Biochar material is a renewable adsorbent widely used for treating contaminated wastewater. The hydrothermal carbon (HTC) were prepared from low polymeric sugars and low concentration glucose under hydrothermal carbonization reactions without using dispersants. The composition and structure of the biochar produced were characterized using X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), Raman spectroscopy (Raman), and N2 adsorption-desorption, indicating that amorphous graphitic carbon was obtained. Experimental results from the static adsorption of Cr(VI)-contaminated wastewater showed that HTCP-2 exhibited the highest adsorption capacity for Cr(VI), with a maximum adsorption capacity of 22.62 mg.g−1.The adsorption Cr(VI), MB, and RhB by the synthesized biochar all conformed to the pseudo-second-order kinetic model and Freundlich isotherm, suggesting a multilayer chemical adsorption process. Additionally, the synthesized HTC surface is enriched with a significant amount of oxygen-rich functional groups, which also has good adsorption performance for cationic dyes. Furthermore, the test results of fluorescence, photocurrent, and impedance indicate that HTCP-2 possesses the ability to generate and separate photoinduced charge carriers. This implied that HTCP-2 can be used for the preparation of adsorption photocatalysts, which effectively remove environmental pollutants through the synergistic effect of adsorption-photocatalysis. This study provides a research foundation for advancing water treatment technologies. Copyright © 2023 by Authors, Published by BCREC Group. This is an open access article under the CC BY-SA License (https://creativecommons.org/licenses/by-sa/4.0).

Selenium Injection in Dam Rabbits During Gestation Has Important Effects on Progeny Productive Performance.

Micromineral elements have a fundamental participation in the processes of organogenesis and fetal development. The objective of this study was to assess the effect of selenium (Se) injection in pregnant female rabbits, during organogenesis or rapid fetal growth, on the productive performance of their progeny. An experiment was carried out with 30 New Zealand female rabbits, with an average age of 6 months. At the end of mating (day 0), using a randomized complete design, the female rabbits were distributed into three experimental groups, which were assigned to the following treatments: Control, female rabbits were injected intramuscularly (IM) with 0.5 ml of saline on days 13 and 23 of gestation; Early administration, female rabbits that were injected IM with Se (0.10 mg/kg BW) on day 13 of gestation (organogenesis) and 0.5 ml of saline on day 23 of gestation; and Late administration, female rabbits that were injected IM with 0.5 ml of saline on day 13 of gestation and Se (0.10 mg/kg BW) on day 23 of gestation (rapid fetal growth). No differences were found on kindling performance of dams and pre-weaning growth of rabbit offspring. However, an injection of Se to pregnant rabbits affected the growth and development of their progeny, with the treatment leading to changes in the yield of some carcass traits (forelimb weight and forelimb muscle weight) and weights of some organs (liver, lungs, and spleen). The Se treatment (both early and late) also resulted in lower concentrations of glucose, triglycerides, and cholesterol when compared to the control group. These effects were different when Se injection was performed during organogenesis or rapid fetal development. The results from this study suggest that there are beneficial effects of gestational Se injection of rabbit dams on important productive traits of their progeny.

Global and Spatial Metabolomics of Individual Cells Using a Tapered Pneumatically Assisted nano-DESI Probe.

Single-cell metabolomics has the potential to reveal unique insights into intracellular mechanisms and biological processes. However, the detection of metabolites from individual cells is challenging due to their versatile chemical properties and concentrations. Here, we demonstrate a tapered probe for pneumatically assisted nanospray desorption electrospray ionization (PA nano-DESI) mass spectrometry that enables both chemical imaging of larger cells and global metabolomics of smaller 15 μm cells. Additionally, by depositing cells in predefined arrays, we show successful metabolomics from three individual INS-1 cells per minute, which enabled the acquisition of data from 479 individual cells. Several cells were used to optimize analytical conditions, and 93 or 97 cells were used to monitor metabolome alterations in INS-1 cells after exposure to a low or high glucose concentration, respectively. Our analytical approach offers insights into cellular heterogeneity and provides valuable information about cellular processes and responses in individual cells.

Reduced glucose concentration enhances ultradian rhythms in Pdcd5 promoter activity in vitro.

Intrinsically driven ultradian rhythms in the hourly range are often co-expressed with circadian rhythms in various physiological processes including metabolic processes such as feeding behaviour, gene expression and cellular metabolism. Several behavioural observations show that reduced energy intake or increased energy expenditure leads to a re-balancing of ultradian and circadian timing, favouring ultradian feeding and activity patterns when energy availability is limited. This suggests a close link between ultradian rhythmicity and metabolic homeostasis, but we currently lack models to test this hypothesis at a cellular level. We therefore transduced 3T3-L1 pre-adipocyte cells with a reporter construct that drives a destabilised luciferase via the Pdcd5 promotor, a gene we previously showed to exhibit robust ultradian rhythms in vitro. Ultradian rhythmicity in Pdcd5 promotor driven bioluminescence was observed in >80% of all cultures that were synchronised with dexamethasone, whereas significantly lower numbers exhibited ultradian rhythmicity in non-synchronised cultures (∼11%). Cosine fits to ultradian bioluminescence rhythms in cells cultured and measured in low glucose concentrations (2mM and 5mM), exhibited significantly higher amplitudes than all other cultures, and a shorter period (6.9h vs. 8.2h, N = 12). Our findings show substantial ultradian rhythmicity in Pdcd5 promotor activity in cells in which the circadian clocks have been synchronised in vitro, which is in line with observations of circadian synchronisation of behavioural ultradian rhythms. Critically, we show that the amplitude of ultradian rhythms is enhanced in low glucose conditions, suggesting that low energy availability enhances ultradian rhythmicity at the cellular level in vitro.

In fission yeast, 65 non-essential mitochondrial proteins related to respiration and stress become essential in low-glucose conditions.

Mitochondria perform critical functions, including respiration, ATP production, small molecule metabolism, and anti-oxidation, and they are involved in a number of human diseases. While the mitochondrial genome contains a small number of protein-coding genes, the vast majority of mitochondrial proteins are encoded by nuclear genes. In fission yeast Schizosaccharomyces pombe, we screened 457 deletion (del) mutants deficient in nuclear-encoded mitochondrial proteins, searching for those that fail to form colonies in culture medium containing low glucose (0.03-0.1%; low-glucose sensitive, lgs), but that proliferate in regular 2-3% glucose medium. Sixty-five (14%) of the 457 deletion mutants displayed the lgs phenotype. Thirty-three of them are defective either in dehydrogenases, subunits of respiratory complexes, the citric acid cycle, or in one of the nine steps of the CoQ10 biosynthetic pathway. The remaining 32 lgs mutants do not seem to be directly related to respiration. Fifteen are implicated in translation, and six encode transporters. The remaining 11 function in anti-oxidation, amino acid synthesis, repair of DNA damage, microtubule cytoskeleton, intracellular mitochondrial distribution or unknown functions. These 32 diverse lgs genes collectively maintain mitochondrial functions under low (1/20-1/60× normal) glucose concentrations. Interestingly, 30 of them have homologues associated with human diseases.

Does the peroral chromium administration in young Hariana calves reduce the risk of calf diarrhea by ameliorating insulin response, lactose intolerance, antioxidant status, and immune response?

BackgroundThe reduction in insulin sensitivity during rumen development may predispose dairy calves towards lactose intolerance, which could be the reason behind neonatal calf diarrhea (NCD). Chromium (Cr) results in a range of effects when fed to ruminants, but most studies have shown improved insulin sensitivity. The aim of this study was to determine the effect of Cr supplementation on insulin sensitivity, lactose intolerance, diarrhoea and antioxidant, and immune response in young Hariana calves. MethodsA total of 20 milk-fed Hariana calves were randomly assigned to 1 of 2 treatments, each consisted of 10 calves: (1) a control group without supplemental Cr and (2) a 0.15 mg Cr as Cr-picolinate (CrPic)/kg BW0.75 supplemented group (Cr0.15). ResultsA more rapid glucose disappearance with unaltered insulin kinetics during intravenous glucose tolerance test (IVGTT) and oral lactose tolerance test (OLTT) indicates greater insulin sensitivity in Cr supplemented calves. Better insulin sensitivity in Cr supplemented calves was further confirmed by higher values of the quantitative insulin sensitivity check index (QUICKI), revised quantitative insulin sensitivity check index (RQUICKI) and insulin receptor substrate-1 (IRS-1) and lower (P < 0.05) values of homeostasis model assessment-insulin resistance (HOMA-IR) and glucose-to-insulin ratio in Cr supplemented calves during IVGTT. Cr supplementation resulted in a lower (P < 0.05) serum cortisol concentration, whereas serum non-esterified fatty acid (NEFA) concentrations during IVGTT did not differ among the groups. The rise in serum glucose concentrations within 2 h post lactose infusion during OLTT peaked at more than twice the basal glucose concentration, therefore calves were not considered as lactose intolerant. Within monthly blood samples, concentrations of serum insulin were similar among treatments, whereas the Cr supplemented group had lower (P < 0.05) serum glucose concentration and glucose-to-insulin ratio compared with the control group. No treatment differences were detected in the biomarkers of antioxidant status and immunity. Serum Cr concentrations were higher (P < 0.05) in Cr supplemented calves while concentrations of other studied minerals were remained unaltered. The incidence, duration of diarrhea, and faecal score were better (P < 0.05) in calves fed on Cr supplemented diet whereas, no treatment effect was observed on average daily gain (ADG). During the study period, no calves died, and no calves were found to have pneumonia, navel or joint disease. ConclusionFeeding a Cr-supplemented diet improved insulin sensitivity and reduced the risk of diarrhoea in milk-fed young calves, but had no or minimal effects on lactose intolerance, antioxidant status, immune response, and growth performance.

Fabrications of the Flexible Non-Enzymatic Glucose Sensors Using Au-CuO-rGO and Au-CuO-rGO-MWCNTs Nanocomposites as Carriers.

A flexible, non-enzymatic glucose sensor was developed and tested on a polyethylene terephthalate (PET) substrate. The sensor's design involved printing Ag (silver) as the electrode and utilizing mixtures of either gold-copper oxide-modified reduced graphene oxide (Au-CuO-rGO) or gold-copper oxide-modified reduced graphene oxide-multi-walled carbon nanotubes (Au-CuO-rGO-MWCNTs) as the carrier materials. A one-pot synthesis method was employed to create a nanocomposite material, consisting of Au-CuO-rGO mixtures, which was then printed onto pre-prepared flexible electrodes. The impact of different weight ratios of MWCNTs (0~75 wt%) as a substitute for rGO was also investigated on the sensing characteristics of Au-CuO-rGO-MWCNTs glucose sensors. The fabricated electrodes underwent various material analyses, and their sensing properties for glucose in a glucose solution were measured using linear sweep voltammetry (LSV). The LSV measurement results showed that increasing the proportion of MWCNTs improved the sensor's sensitivity for detecting low concentrations of glucose. However, it also led to a significant decrease in the upper detection limit for high-glucose concentrations. Remarkably, the research findings revealed that the electrode containing 60 wt% MWCNTs demonstrated excellent sensitivity and stability in detecting low concentrations of glucose. At the lowest concentration of 0.1 μM glucose, the nanocomposites with 75 wt% MWCNTs showed the highest oxidation peak current, approximately 5.9 μA. On the other hand, the electrode without addition of MWCNTs displayed the highest detection limit (approximately 1 mM) and an oxidation peak current of about 8.1 μA at 1 mM of glucose concentration.

Zirconium copper oxide microflowers based non-enzymatic screen-printed electrochemical sensor for the detection of glucose in saliva, urine, and blood serum.

Zirconium copper oxide microflowers (Zr/CuO MF) based non-enzymatic sensor was developed for glucose detection in saliva, urine, and blood. An easy urea hydrolysis method was employed for the synthesis of the metal oxide and further calcined to improve the catalytic property. The flower-like morphology of the Zr/CuO was confirmed by SEM analysis and the presence of copper and zirconium was examined using energy dispersive X-ray analysis (EDAX). The Zr/CuO MF modified screen-printed electrodes exhibited excellent glucose sensing performance in 0.15M NaOH medium and could quantify glucose in the range from 10µM to 27mM. A high sensitivity of 1.815 ± 0.003mAmM-1cm-2 was obtained for lower glucose concentration from 15µM to 3mM and 1.250 ± 0.006mAmM-1cm-2 for higher concentration glucose from 3 to 27mM. The limit of detection of the fabricated sensor was found to be 0.8µM. The sensor displayed high selectivity and stability towards glucose in different body fluids like saliva, urine, and blood serum at a working potential of 0.6V (vs. Ag/AgCl). In saliva, urine, and serum samples, the sensor exhibited excellent recovery of 95-108, 92-108, and 93-101% in saliva, urine, and serum, respectively, with a relative standard deviation of less than 10%, demonstrating high accuracy and reliability of the sensor. The developed sensor is promising for developing an invasive and non-invasive point-of-care testing device for glucose detection.

Serum/Faecal S100A12, CRP and lactoferrin can be used to distinguish ınfectious and non-ınfectious canine diarrhoea.

This study aimed to evaluate the diagnostic efficacies of selected inflammatory and intestinal biomarkers in cases of infectious and non-infectious diarrhoea in dogs. A total of 60 dogs, 12 healthy (Control Group) and 48 with diarrhoea were used. Viral, Bacterial, Parasitic (infectious) and Nutritional diarrhoea (non-infectious) subgroups (n: 12) were formed according to the aetiology, on the basis of clinical and laboratory examinations. Selected inflammatory and intestinal biomarkers (Calgranulin, S100A12; Lactoferrin, LCTF; C-reactive protein, CRP) were measured both in serum and faecal samples. Compared to the Control and Nutritional Diarrhoea groups, the infectious diarrhoea groups had higher serum S100A12, LCTF, CRP, blood urea nitrogen, creatinine (CR), alanine transaminase and alkaline phosphatase, and lower glucose (GLU), sodium (Na) and potassium (K) concentrations (p<0.05); Viral and Parasitic Diarrhoea groups had lower serum albumin (ALB) and total protein (TP) concentrations (p<0.05). Faecal S100A12, LCTF and CRP concentrations were higher in infectious diarrhoea groups compared to the Control and Nutritional Diarrhoea groups (p<0.05). Faecal LCTF and CRP concentrations were higher in the Bacterial Diarrhoea group than in the Viral and Parasitic Diarrhoea groups (p<0.05). It was determined that serum (area under curve, AUC: 0.842 and 0.956) and faecal (AUC: 0.975 and 0.786) S100A12 and CRP concentrations in viral diarrhoea; serum (AUC: 0.956) and faecal (AUC: 0.992) LCTF concentrations in bacterial diarrhoea have diagnostic values in the diagnosis of the presence of intestinal inflammation and damage and can be used in the differential diagnosis of infectious and non-infectious diarrhoea.

Glucose Starvation Stimulates the Promoting Strength of a Novel Evolved Suc2 Promoter.

Promoters are essential for designing Saccharomyces cerevisiae cell factories. Identifying novel promoters tuned to produce specific metabolites under increasingly diverse industrial stresses is required to improve the economic feasibility of whole fermentation processes. In this study, a positively evolved Suc2 promoter (SUC 2p) with promoter activity stronger than that of the wild-type Suc2 promoter (SUC 2wtp) was obtained. Quantitative real-time PCR, fluorescence analysis, Western blotting, and a β-galactosidase activity assay revealed that SUC 2p is a medium-strength promoter compared with eight reported promoters at a medium glucose concentration (2% (w/v)). Different glucose concentrations modulated the strength of SUC 2p. Low glucose concentrations (0.05 and 0.5% (w/v)) enhanced the promoter strength of SUC 2p dramatically, with promoter activity higher than that of reported strong promoters. Glucose starvation resulted in the formation of a new Msn2/4 binding site on SUC 2p. Our work should facilitate the development of promoters with novel fine-tuning properties and the construction of S. cerevisiae cell factories suitable for the industrial production of essential chemicals under glucose-deprived conditions.

Hypoglycaemia Among Diabetes Patients: A Preventive Approach

Hypoglycaemia is a low blood glucose concentration and an indicator of diabetes mellitus, and are associated with physical and psychological morbidity. It is a common, potentially avoidable consequence of diabetes treatment, and a major barrier to better metabolic control in diabetes. It is due to overtreatment of diabetes patients with insulin or sulfonylureas or glinides or also consumption of too little food or unplanned excessive exercise or physical activity. It is the acute complication of diabetes and is associated with considerable morbidity and mortality. It is important of the early recognition, treatment, and prevention of hypoglycaemia. Immediate treatment of severe hypoglycaemia is needed to avoid life threatening complications of the diabetic patients. In this study an attempt has been taken to discuss the aspects of hypoglycaemia of diabetes mellitus patients.

The Role of Glucose Concentration and Resveratrol in Modulating Neuroinflammatory Cytokines: Insights from an In Vitro Blood-Brain Barrier Model.

BACKGROUND The prevalence of type 2 diabetes mellitus is rising, presumably because of a coexisting pandemic of obesity. Since diabetic neuropathy and neuroinflammation are frequent and significant complications of both prolonged hyperglycemia and iatrogenic hypoglycemia, the effect of glucose concentration and resveratrol (RSV) supplementation on cytokine profile was assessed in an in vitro model of the blood-brain barrier (BBB). MATERIAL AND METHODS The in vitro model of BBB was formed of endothelial cells and astrocytes, which represented the microvascular and brain compartments (MC and BC, respectively). The BC concentrations of selected cytokines - IL-10, IL-12, IL-17A, TNF-alpha, IFN-γ, GM-CSF in response to different glucose concentrations in the MC were studied. The influence of LPS in the BC and RSV in the MC on the cytokine profile in the BC was examined. RESULTS Low glucose concentration (40 mg/dL) in the MC resulted in increased concentration of all the cytokines in the BC except TNF-alpha, compared to normoglycemia-imitating conditions (90 mg/dL) (P<0.05). High glucose concentration (450 mg/dL) in the MC elevated the concentration of all the cytokines in the BC (P<0.05). RSV decreased the level of all cytokines in the BC after 24 h following its administration for all glucose concentrations in the MC (P<0.02). The greatest decline was observed in normoglycemic conditions (P<0.05). CONCLUSIONS Both hypo- and hyperglycemia-simulating conditions impair the cytokine profile in BC, while RSV can normalize it, despite relatively poor penetration through the BBB. RSV exhibits anti-neuroinflammatory effects, especially in the group with normoglycemia-simulating conditions.

Submerged fermentation using Aspergillus tubingensis as an efficient strategy to obtain antioxidant extracts from black cricket proteins

In recent years, there has been growing interest in edible insects as a novel food source due to their high nutritional value and more sustainable cultivation system compared to traditional animal sources. Edible insects are rich in proteins, which can be used to produce bioactive peptides through enzymatic hydrolysis or fermentation. The main objective of this study was to evaluate the production of an antioxidant extract using proteins extracted from the black cricket (Gryllus assimilis) as a substrate for the submerged fermentative process conducted by the filamentous fungus Aspergillus tubingensis. A response surface methodology (CCRD) was employed to investigate the effect of glucose and black cricket protein concentrations in the culture medium on the release of the peptides. The results demonstrated that the maximum values for DPPH (290.79 µmol TE g–1), ABTS (862.82 µmol TE g–1), and FRAP (1020.11 µmol TE g–1) were obtained at 72 or 96 h of fermentation using lower concentrations of both protein and glucose. These findings confirm that black cricket proteins are suitable for producing an antioxidant extract via microbial fermentation.

The Slight Adjustment in the Weight of Sulfur Sheets to Synthesize β-NiS Nanobelts for Maintaining Detection of Lower Concentrations of Glucose through a Long-Term Storage Test.

The β-nickel sulfide (β-NiS) nanobelts were fabricated by electrodepositing a nickel nanosheet film on Indium tin oxide (ITO)-coated glass substrates and sulfuring the nickel film on ITO-coated glass substrates. The sulfurization method can be used to form nanobelts without a template. A small glass tube was used to anneal the sulfur sheet with a nickel nanosheet film. After applying vacuum to the tube, the specimen was annealed at 500 °C. By adjusting the weight of the sulfur sheet in a small glass tube, a nanobelt structure can be formed on the film for 4 h. The β-NiS nanobelt film had a sulfide and nickel molar ratio that was nearly 0.7 (S/Ni). After five years of a long-term storage test, the β-NiS nanobelt films were able to measure the glucose in a solution with the value of sensitivity of 8.67 µA cm-2 µM-1. The β-NiS nanobelt film also detected glucose with a limit of low detection (LOD) of around 0.173 µM. The estimation of reproducibility was over 98%. Therefore, the β-NiS nanobelt film has a significant ability to detect low concentrations of glucose in a solution.

Alterations in Mitochondrial Morphology and Quality Control in Primary Mouse Lung Microvascular Endothelial Cells and Human Dermal Fibroblasts under Hyperglycemic Conditions.

The effect of hyperglycemia on the morphology of individual mitochondria and the state of the mitochondrial network in primary mouse lung microvascular endotheliocytes and human dermal fibroblasts has been investigated. The cells were exposed to high (30 mM) and low (5.5 mM) glucose concentrations for 36 h. In primary endotheliocytes, hyperglycemic stress induced a significant increase in the number of mitochondria and a decrease in the interconnectivity value of the mitochondrial network, which was associated with a decrease in the mean size of the mitochondria. Analysis of the mRNA level of the genes of proteins responsible for mitochondrial biogenesis and mitophagy revealed an increase in the expression level of the Ppargc1a, Pink1, and Parkin genes, indicating stimulated mitochondrial turnover in endotheliocytes under high glucose conditions. In primary fibroblasts, hyperglycemia caused a decrease in the number of mitochondria and an increase in their size. As a result, the mitochondria exhibited higher values for elongation. In parallel, the mRNA level of the Ppargc1a and Mfn2 genes in fibroblasts exposed to hyperglycemia was reduced. These findings indicate that high glucose concentrations induced cell-specific morphological rearrangements of individual mitochondria and the mitochondrial network, which may be relevant during mitochondria-targeted drug testing and therapy for hyperglycemic and diabetic conditions.