Excess Glucose Research Articles

1736-P: Effect of Glucokinase Haploinsufficiency on Pancreatic Beta-Cell Function and Mass in High-Fat, High-Sucrose Diet-Fed Mice

Background and Aim: We previously found in db/db mice that glucokinase haploinsufficiency reduces excessive glucose signaling in beta-cells and optimizes intracellular metabolic patterns, thereby preserving pancreatic beta-cell function and mass, ultimately improving glucose tolerance. In the present study, we investigated the effect of glucokinase haploinsufficiency on beta-cell function and mass in high-fat, high-sucrose diet (HFHS)-fed mice. Method: Four-week-old male wild-type (Gck+/+) and glucokinase haploinsufficient (Gck+/−) mice were fed normal chow (NC) or HFHS. Blood glucose levels were measured, and glucose tolerance, glucose-stimulated insulin secretion (GSIS), and pancreatic beta-cell mass were evaluated over time (16, 40, and 60 weeks of age). Results: At 16 weeks of age, no difference was found in glucose tolerance between NC and HFHS feeding in both Gck+/+ and Gck+/− mice. At 40 weeks of age, Gck+/+ HFHS-fed mice exhibited increases in GSIS and beta-cell mass versus Gck+/+ NC-fed mice (7.0 ± 1.2 mg vs. 3.3 ± 1.6 mg; P < 0.01), and glucose tolerance was preserved. Conversely, Gck+/− HFHS-fed mice displayed no increase in beta-cell mass (4.1 ± 0.5 mg vs. 3.9 ± 1.5 mg), a slight increase in GSIS, and worsening of glucose tolerance compared with Gck+/− NC-fed mice. At 60 weeks of age, Gck+/+ HFHS-fed mice displayed further increases in beta-cell mass (14.7 ± 2.0 mg) and GSIS with no worsening of glucose tolerance. In Gck+/− HFHS-fed mice, beta-cell mass (5.5 ± 1.4 mg) and GSIS were partially increased, and no further worsening of glucose tolerance was observed after 40 weeks of age. Conclusion: Gck+/− mice fed HFHS displayed insufficient increases in beta-cell mass and GSIS, resulting in worsening of glucose tolerance. In the longer term, however, these mice did not exhibit subsequent declines in beta-cell mass and GSIS nor progressive worsening of glucose tolerance unlike the non-compensatory phase in people with type 2 diabetes. Disclosure I.Shigesawa: None. T.Atsumi: Speaker's Bureau; Eli Lilly Japan K.K., Kowa Company, Ltd. A.Nakamura: Research Support; Abbott Japan Co., Ltd., Boehringer Ingelheim Japan, Inc., Daiichi Sankyo, Taisho Pharmaceutical Holdings Co., Ltd., Teijin Pharma Limited, Kowa Company, Ltd., Mitsubishi Tanabe Pharma Corporation. Y.Yamauchi: None. S.Kawata: None. A.Miyazaki: None. H.Nomoto: Speaker's Bureau; Novo Nordisk, Sumitomo Pharma, Co., Ltd. H.Kameda: None. H.Miyoshi: Research Support; Abbott, LifeScan Diabetes Institute, Taisho Pharmaceutical Holdings Co., Ltd., Speaker's Bureau; AstraZeneca, Boehringer Ingelheim Japan, Inc., Eli Lilly Japan K.K., Kowa Company, Ltd., MSD Life Science Foundation, Novo Nordisk, Ono Pharmaceutical Co., Ltd., Sanofi K.K., Mitsubishi Tanabe Pharma Corporation. Y.Terauchi: Advisory Panel; Novo Nordisk, Eli Lilly Japan K.K., Sanofi, AstraZeneca, MSD Life Science Foundation, Consultant; Astellas Pharma Inc., Research Support; Abbott Japan Co., Ltd., Boehringer Ingelheim Japan, Inc., Mitsubishi Tanabe Pharma Corporation, Daiichi Sankyo, Novo Nordisk, Eli Lilly Japan K.K., Sanofi, Sumitomo Dainippon Pharma Co., Ltd., Kyowa Kirin Co., Ltd., Speaker's Bureau; Kowa Company, Ltd., Merck Sharp & Dohme Corp., Ono Pharmaceutical Co., Ltd., Abbott Japan Co., Ltd., Boehringer Ingelheim Japan, Inc., Novartis Pharmaceuticals Corporation, Mitsubishi Tanabe Pharma Corporation, Daiichi Sankyo, Sanwa Kagaku Kenkyusho, Novo Nordisk, Eli Lilly Japan K.K., Sanofi, Sumitomo Dainippon Pharma Co., Ltd., Astellas Pharma Inc., AstraZeneca, Taisho Pharmaceutical Holdings Co., Ltd., Medtronic, Teijin Pharma Limited, Roche Diagnostics, LifeScan Diabetes Institute, Terumo Corporation, Bayer Inc., Eisai Co., Ltd., Takeda Pharmaceutical Co., Ltd., Kyowa Kirin Co., Ltd.

Role of sodium pyruvate in maintaining the survival and cytotoxicity of Staphylococcus aureus under high glucose conditions.

Glucose is a crucial carbon source for the growth of Staphylococcus aureus, but an excess of glucose is detrimental and even leads to cell death. Pyruvate, the central metabolite of glycolysis, has been shown to have anti-inflammatory and antioxidant properties. This study aimed to investigate the protective effect of pyruvate on S. aureus under high glucose conditions. Sodium pyruvate greatly increased the cytotoxicity of S. aureus strain BAA-1717 to human erythrocytes and neutrophils in vitro. However, the cytotoxicity and survival of S. aureus were significantly reduced by high glucose, which was restored to normal levels by the addition of sodium pyruvate. The expression of hlg and lukS in S. aureus was higher in the LB-GP cultures than that in LB-G cultures, but there was no significant difference in cytotoxicity between LB-GP and LB-G cultures. Furthermore, the hemolytic activity of S. aureus supernatants could be inhibited by the cell-free culture medium (CFCM) of LB-G cultures, suggesting that high levels of extracellular proteases were presence in the CFCM of LB-G cultures, resulting in degradation of the hemolytic factors. The expression of sarA, which negatively regulates extracellular protease secretion, was higher in LB-GP cultures than that in LB-G cultures. Additionally, sodium pyruvate increased acetate production in S. aureus, which helps maintain cell viability under acidic environment. In conclusion, pyruvate plays an important role in the survival and cytotoxicity of S. aureus under high glucose conditions. This finding may aid in the development of effective treatments for diabetic foot infections.

Differential effects of sugar and fat on adipose tissue inflammation

Obese individuals experience low grade inflammation initiated within their adipose tissue. However, the early events that lead to the release of these inflammatory factors from adipose tissue are poorly characterized. To separate glucose effects from lipid effects on adipose tissue, we used an adipose-specific TXNIP knockout model where excess basal glucose influx into adipocytes led to modest increase in adiposity without using high fat diet. We found an uncoupling of two events that are generally presumed to be coregulated: (1) an increase of adipose tissue macrophage (ATM) number; and (2) pro-inflammatory activation of ATMs. These two events are associated with different triggering signals: elevated free fatty acids output and extracellular matrix remodeling with increased ATM number, whereas decreased adiponectin level with activated ATM. This separation reflects non-overlapping pathways regulated by glucose and lipids in adipocytes, and neither group alone is sufficient to elicit the full inflammatory response in adipose tissue.

The Impact of Hypothyroidism on Diabetes Mellitus and Its Complications: A Comprehensive Review.

Diabetes mellitus (DM) is one of the most prevalent metabolic disorders in the world and is characterized by excessive blood glucose levels, which lead to deranged carbohydrate, protein, and lipid metabolisms. At its core, DM is an impairment of insulin metabolism, leading to a plethora of clinical features. The thyroid gland is another vital cog in the wheel of the endocrine system, and the hormones synthesized by it are heavily involved in the control of the body's metabolism. Hypothyroidism is a state in which thyroid hormones are deficient due to various factors and is characterized by a metabolically hypoactive state. Together, insulin, implicated in DM, and thyroid hormones engage in an intricate dance and serve to regulate the body's metabolism. It is imperative to explore the relationship between these two common endocrine disorders to understand their clinical association and mold treatments specific to patients in which they coexist. Both type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM) have been shown to have an increased association with hypothyroidism, especially in patients with risk factors including female sex, hyperlipidemia, obesity, and anemia. This review also explores DM's macrovascular and microvascular complications and their association with hypothyroidism. It is of great use to screen for hypothyroidism in diabetic patients. Specific protocols, especially for patients at an elevated risk, provide improved quality of life to patients affected by this highly prevalent disease.

Effects of Diabetes Mellitus-Related Dysglycemia on the Functions of Blood-Brain Barrier and the Risk of Dementia.

Diabetes mellitus is one of the most common metabolic diseases worldwide, and its long-term complications include neuropathy, referring both to the peripheral and to the central nervous system. Detrimental effects of dysglycemia, especially hyperglycemia, on the structure and function of the blood-brain barrier (BBB), seem to be a significant backgrounds of diabetic neuropathy pertaining to the central nervous system (CNS). Effects of hyperglycemia, including excessive glucose influx to insulin-independent cells, may induce oxidative stress and secondary innate immunity dependent inflammatory response, which can damage cells within the CNS, thus promoting neurodegeneration and dementia. Advanced glycation end products (AGE) may exert similar, pro-inflammatory effects through activating receptors for advanced glycation end products (RAGE), as well as some pattern-recognition receptors (PRR). Moreover, long-term hyperglycemia can promote brain insulin resistance, which may in turn promote Aβ aggregate accumulation and tau hyperphosphorylation. This review is focused on a detailed analysis of the effects mentioned above towards the CNS, with special regard to mechanisms taking part in the pathogenesis of central long-term complications of diabetes mellitus initiated by the loss of BBB integrity.

Excess glucose or fat differentially affects metabolism and appetite-related gene expression during zebrafish embryogenesis

Zebrafish embryos use their yolk sac reserve as the sole nutrient source during embryogenesis. The two main forms of energy fuel can be found in the form of glucose or fat. Zebrafish embryos were exposed to glucose or injected with free fatty acid/Triacylglycerol (FFA/TAG) into the yolk sac at 24 hpf. At 72 hpf, glucose exposed or FFA/TAG injected had differential effects on gene expression in embryos, with fat activating lipolysis and β-oxidation and glucose activating the insulin pathway. Bulk RNA-seq revealed that more gene expression was affected by glucose exposure compared to FFA/TAGs injection. Appetite-controlling genes were also differently affected by glucose exposure or FFA/TAG injections. Because the embryo did not yet feed itself at the time of our analysis, gene expression changes occurred in absence of actual hunger and revealed how the embryo manages its nutrient intake before active feeding.

Altered brain energy metabolism related to astrocytes in tauopathies

AbstractBackgroundAccumulated evidence suggests altered energy metabolism in the brain of tauopathies. In Alzheimer’s disease (AD) and progressive supranuclear palsy (PSP), decreased fluorodeoxyglucose (FDG) uptake in the cingulate cortex is considered a marker of neurodegeneration. However, its underlying pathogenesis remains unknown. It is hypothesized that lactate, a glucose metabolite, is produced in astrocytes and subsequently shuttles to neurons as an energy substrate. The current study aims to examine alterations in lactate and glucose concentrations and their association with astrocytic activities in the cingulate cortex of patients with AD and PSP.MethodThirty AD, 30 PSP, and 30 healthy control (HC) subjects were enrolled. Lactate, glucose, and myoinositol (mI), an astroglial marker, in the anterior cingulate cortex (ACC) and posterior cingulate cortex (PCC) were determined by magnetic resonance spectroscopy (MRS) (3T scanner, SPECIAL sequence, TR/TE 3000/8.5ms, LCModel analysis) (Figure 1). Tau depositions were assessed using PET imaging with 18F‐PM‐PBB3.ResultAll the patients with AD and PSP were confirmed to have the typical distribution of tau pathology. Lactate, glucose, and mI levels were higher in the ACC in PSP and AD, and PCC in AD compared to HC (p < 0.05) (Figure 2). In these cortical regions, lactate levels showed a positive correlation with mI levels (p < 0.05) (Figure 3). Lactate levels in the PCC in AD patients showed a positive correlation with Clinical Dementia Rating‐Sum of Boxes (CDR‐SB) scores (p < 0.05) (Figure 4). Moreover, mI levels in the ACC in PSP patients were negatively correlated with Frontal Assessment Battery (FAB) scores (p < 0.05) (Figure 4).ConclusionWe found elevated lactate and glucose levels accompanied by an increased astroglial marker mainly in the PCC in AD and ACC in PSP patients. Moreover, elevated lactate and mI levels in the cingulate cortex reflected the cognitive decline of AD and PSP, respectively. The excess lactate and glucose levels in the disease‐specific regions might reflect decreased energy utilization as shown in previous FDG‐PET studies. Given the residual lactate levels were correlated with mI levels, we speculated that the impaired lactate shuttle of reactivated astrocytes disrupts energy metabolism, leading to cognitive dysfunctions.

The Association of Asymptomatic Urinary Tract Infection (UTI) with Diabetes Mellitus (DM) in Pregnant Women

Background: Urinary tract infection (UTI) is a common infection of diabetic pregnant women because of excess urine glucose excretion and lowered immunity. UTI during pregnancy is directly proportionate to maternal and neonatal complications. Diabetes mellitus (DM) and urological health problems are closely related during pregnancy. DM patients are prone to UTI, bladder issues and sexual dysfunction. The intent of the study was to find out the association of asymptomatic urinary tract infection (UTI) with diabetes mellitus (DM) in pregnant women. Material & Methods: A prospective cross-sectional study was carried out in the Department of Public Health of Varendra University in Bangladesh for the duration of 4 months in the summer session from May 2018 to August 2018. All the pregnant mothers (N=119) with diabetes mellitus in Chapai Nawabganj during the study period constituted the study population. Ethical clearance was taken from the hospital. The data analysis was performed using Statistical Package for the Social Sciences (SPSS) Version 25.0. Results: Among the study population (N=119), the mean age of the respondents was 25.14 ± 4.82 years, and most of the respondents were in the age group of below 25 years. It was observed that around one-third of the respondents (36,30.3%) monthly income was up to 15,000 taka. Regarding the duration of gestation, it was observed that the mean duration of gestation was 19.06 ± 5.62 weeks. Around one-fourth of the respondents (33,27.7%) had good but unhygienic sanitation and the majority of them (78,65.5%) had good and hygienic sanitation conditions. It was recognized that the majority of the respondents (82,68.9%) had 6-8 times of micturition per day. Sixty-two respondents who had DM did not know about UTI and the relationship between the pattern of DM and urinary tract infection was not found statistically significant (p>0.05). Conclusion: In the case of pregnancy, in women with DM, UTI is the most commonly noticed maternal infection. The findings provided by the analysis might help in the management of asymptomatic urinary tract infections during pregnancy.

The Effect of Overnutrition on Mediated Collagen in Drosophila Melanogaster Physiology

Obesity affects approximately 13% of the adult population, resulting in excessive fat cell deposition and metabolic dysfunction. Collagen, a protein that supports skin regeneration, muscle building, and pain relief, is studied in Drosophila melanogaster under different diet conditions. This experiment aims to test whether overnutrition affects physiology and collagen due to any anatomical changes in Drosophila Melanogaster, more commonly known as fruit flies. The research conducted over several weeks utilizes two diets: an obesity-inducing diet containing excessive glucose and coconut oil and a traditional diet of blue food medium, yeast, and water. The study groups include a wild-type, collagen-mutated, and obesity-mutated group, with multiple assays measuring how the obesity-inducing diet affects each population and their collagen levels. The results reveal that the obese group experienced higher food consumption levels but had lower locomotive ability than the other test groups. Hydroxyproline, the building amino acid for collagen, and collagen levels were higher in the obesity mutant than in the wild-type and collagen mutated group. The study shows that anatomical changes in organisms are influenced by both diet and movement. The obesity group, on an obesity-inducing diet, experienced decreased movement related to increased food intake and decreased neural activity. The high-fat and high-sugar diet suppressed neuronal autophagy, created inaccurate hunger and satiety perceptions, and increased collagen deposition. Anatomical changes were observed in collagen-heavy tissue areas, whereas decreased neural activity and increased feeding rates were behavioral changes. The study emphasized the importance of a healthy diet and exercise in promoting overall health.

Tracer metabolomics reveals the role of aldose reductase in glycosylation

Abnormal polyol metabolism is predominantly associated with diabetes, where excess glucose is converted to sorbitol by aldose reductase (AR). Recently, abnormal polyol metabolism has been implicated in phosphomannomutase 2 congenital disorder of glycosylation (PMM2-CDG) and an AR inhibitor, epalrestat, proposed as a potential therapy. Considering that the PMM2 enzyme is not directly involved in polyol metabolism, the increased polyol production and epalrestat's therapeutic mechanism in PMM2-CDG remained elusive. PMM2-CDG, caused by PMM2 deficiency, presents with depleted GDP-mannose and abnormal glycosylation. Here, we show that, apart from glycosylation abnormalities, PMM2 deficiency affects intracellular glucose flux, resulting in polyol increase. Targeting AR with epalrestat decreases polyols and increases GDP-mannose both in patient-derived fibroblasts and in pmm2 mutant zebrafish. Using tracer studies, we demonstrate that AR inhibition diverts glucose flux away from polyol production toward the synthesis of sugar nucleotides, and ultimately glycosylation. Finally, PMM2-CDG individuals treated with epalrestat show a clinical and biochemical improvement.

Targeted lipidomics reveals a novel role for glucosylceramides in glucose response

The addition of excess glucose to the diet drives a coordinated response of lipid metabolism pathways to tune the membrane composition to the altered diet. Here, we have employed targeted lipidomic approaches to quantify the specific changes in the phospholipid and sphingolipid populations that occur in elevated glucose conditions. The lipids within wild-type Caenorhabditis elegans are strikingly stable with no significant changes identified in our global mass spectrometry–based analysis. Previous work has identified ELO-5, an elongase that is critical for the synthesis of monomethyl branched-chain fatty acids (mmBCFAs), as essential for surviving elevated glucose conditions. Therefore, we performed targeted lipidomics on elo-5 RNAi-fed animals and identified several significant changes in these animals in lipid species that contain mmBCFAs as well as in species that do not contain mmBCFAs. Of particular note, we identified a specific glucosylceramide (GlcCer 17:1;O2/22:0;O) that is also significantly upregulated with glucose in wild-type animals. Furthermore, compromising the production of the glucosylceramide pool with elo-3 or cgt-3 RNAi leads to premature death in glucose-fed animals. Taken together, our lipid analysis has expanded the mechanistic understanding of metabolic rewiring with glucose feeding and has identified a new role for the GlcCer 17:1;O2/22:0;O.

Transcriptome Analysis to Elucidate the Effects of Milk Replacer Feeding Level on Intestinal Function and Development of Early Lambs.

Although early feeding strategies influence intestinal development, the effects of milk replacer (MR) feeding level on intestinal structure and functional development and underlying regulatory mechanisms remain unclear. In this study, 14 male Hu lambs were fed MR at 2% or 4% of their average body weight and weaned at 35 days of age. The MR was produced by the Institute of Feed Research of the Chinese Academy of Agricultural Sciences, and it contains 96.91% dry matter, 23.22% protein, and 13.20% fat. Jejunal tissues were assessed by RNA-seq for differences in the gene expression of lambs at 49 days of age; regulatory pathways and mechanisms of the effects of early nutrition on intestinal function and development were analyzed, along with growth performance, feed intake, jejunal histomorphology, and digestive enzyme activities. Increasing MR- feeding levels increased dry matter intake and daily gain before weaning, as well as lactase, amylase, lipase, trypsin, and chymotrypsin activities and intestinal villus length and muscular thickness. Overall, 1179 differentially expressed genes were identified, which were enriched in nutrient metabolism, coagulation cascades, and other pathways. Further, intensive MR feeding affected insulin sensitivity to reduce excessive glucose interception by intestinal tissues to ensure adequate absorbed glucose release into the portal circulation and promoted lipid and protein degradation in intestinal tissues to meet the energy demand of intestinal cells by regulating AHSG, IGFBP1, MGAT2, ITIH, and CYP2E1 expression.

Сучасний погляд на патогенетичні механізми діабетичної ретинопатії

Diabetes mellitus (DM) and its complications are an actual problem of modern medicine. This pathology continues to spread throughout the world like a non-infectious epidemic. In this review new data about the role of different cellular mechanisms in forming of diabetic retinopathy (DR), namely, oxidative-nitrosative stress, mitochondrial dysfunction, neurodegeneration and inflammation. A new approach to DR pathogenesis is the primacy of the neurodegenerative changes in the retina vs previously held views of the problem as а microvascular pathology of the eye only. At the moment, hyperglycemia is considered as the main etiological factor of DR. Activation of the oxidation of excess glucose triggers a cascade of reactions with the formation of oxidative and nitrosative stress. Mitochondria are the most sensitive to oxidative-nitrosative organelles in cells of the retina. Hyperglicemia-induced mitochondrial dysfunction, with cellular respiration disruption and increased production of free radicals in neurons of the retina, can promote their further degeneration and DR enhancing. Local inflammation in the retina, which is facilitated in DM, also considered as a new component of DR pathogenesis. In this case, the inflammatory cascade occurs at the molecular level without clinical manifestations of inflammation. The review provides analysis of modern literature data on this mechanism involving in retinal complications of DM. It is emphasized, that retinal inflammation in DM enhances neurodegeneration and promote retinopathy.

Disproportionate Fetal Abdominal Growth in Patients With Diabetes Does Not Increase the Risk of Neonatal Hypoglycemia [ID: 1369330

INTRODUCTION: Neonates of pregnant persons with diabetes are at increased risk of hypoglycemia. The Fetal Abdominal Adiposity Score (FAAS) is a measure of disproportionate fetal abdominal growth theorized to serve as a proxy for fetal exposure to excess glucose in utero. We sought to characterize the relationship between FAAS and neonatal hypoglycemia in this population. METHODS: Pregnancies complicated by gestational diabetes (GDM), or preexisting diabetes type 1 (T1DM) or type 2 (T2DM), resulting in delivery of a live singleton nonanomalous fetus were identified within an existing NIH-funded database. Corresponding third-trimester ultrasounds (US) were identified. The FAAS was calculated as follows for each pregnancy, using measurements from the last US prior to delivery: fetal biparietal diameter minus fetal abdominal diameter (calculated as abdominal circumference/π). Results were expressed as a percentile for the gestational age at measurement relative to a reference population. Clinically significant neonatal hypoglycemia was defined as a hypoglycemia that either required treatment or resulted in a blood glucose level of 25 mg/dL or lower in the first 24 hours of life. RESULTS: Clinically significant hypoglycemia occurred in 58/1,299 neonates (4.5%), including 0/39 (0%) with FAAS at the 10th centile and 11/229 (4.8%) with FAAS at the 90th centile. There was no statistically significant difference in risk of hypoglycemia between various FAAS categories (P=.133). FAAS was weakly associated with the lowest postnatal blood sugar (R=0.098). CONCLUSION: Among pregnancies complicated by diabetes, FAAS was not associated with risk of neonatal hypoglycemia even for those at the extremes of abdominal growth.

ANTIDIABETIC ACTIVITY TEST OF ETHANOL EXTRACT BROCOLI (BRASSICA OLERACEA VAR. ITALICA) IN WHITE MALE RATS

Diabetes is a chronic disease characterized by excessive blood glucose levels caused by absolute and relative insulin deficiency. The stages in this study were sampling, identification of samples/plants, simplification, simplification screening, and preparation of extracts by maceration. The method used in the diabetes activity test uses a glucometer to induce alloxan in rats at a dose of 150 mg/kg body weight. The test animals were 25 rats which were divided into 5 treatment groups namely CMC Na 0.5% (negative control), glibenclamide (positive control) 0.45 mg/kg body weight and EEB dose 200 mg/kg body weight, 400 mg/kg body weight and 600. mg/kg body weight. kg B.W. kg body weight as a test material given orally. Measurement of blood glucose values ​​according to Allox and on days 3, 5, and 7 after administration of the test substance, namely EEB. The test results data were analyzed statistically using one-way ANOVA at a 95% confidence level followed by Tukey's post hoc test. The results of the phytochemical screening showed that EEB contains alkaloids, flavonoids, tannins, saponins, and glycosides. The results of the diabetes efficacy test showed that EEB doses of 200, 400, and 600 mg/kg BW had an anti-diabetic effect on male white rats. The EEB dose of 600 mg/kg is the most effective. Post hoc Tukey test results showed that EEB doses of 200 mg/kg, 400 mg/kg, and 600 mg/kg were not significantly different from the positive control glibenclamide 0.45 mg/kg (p>0.05) and 200,400 ug. and 600 mg/kg BW were significantly different from the negative control CMC Na 0.5% (p<0.05).

Modified Cassava Starches’ Identification through Mid-Infrared Spectroscopy and Exploratory Analysis

Different starch properties may cause alterations in the foodstuff’s external appearance. However, modification processes in starches are usually secretive. The use of chemically modified starches is regulated by international standards, which makes it important to identify its presence and type. Mid-infrared spectroscopy (MIR)-modified starches’ identification can be hindered by the presence of excess glucose. This research investigates types of modification in commercial starches and in approaches that circumvent MIR’s limitations with exploratory analysis. It also considers that enzymatic hydrolysis (α-amylase and amyloglucosidase) can highlight the points of modification in the structure, which can be detected with infrared assays. To determine if sour cassava starch (FCS) is modified and check its type, six samples were selected: a native one, three of the most common cassava modified starches (etherified, esterified, and FCS), and two laboratory processed samples (Acid, Oxidized). The results showed that the sour cassava starch showed similarities with a commercial ester and an oxidized cassava starch, which may be due to the formation of a graft, corresponding to what the literature has already reported for corn starch treated with lactic acid and gamma radiation.

Astrocytic aerobic glycolysis provides lactate to support neuronal oxidative metabolism in the hippocampus.

Under physiological conditions, the energetic demand of the brain is met by glucose oxidation. However, ample evidence suggests that lactate produced by astrocytes through aerobic glycolysis may also be an oxidative fuel, highlighting the metabolic compartmentalization between neural cells. Herein, we investigate the roles of glucose and lactate in oxidative metabolism in hippocampal slices, a model that preserves neuron-glia interactions. To this purpose, we used high-resolution respirometry to measure oxygen consumption (O2 flux) at the whole tissue level and amperometric lactate microbiosensors to evaluate the concentration dynamics of extracellular lactate. We found that lactate is produced from glucose and transported to the extracellular space by neural cells in hippocampal tissue. Under resting conditions, endogenous lactate was used by neurons to support oxidative metabolism, which was boosted by exogenously added lactate even in the presence of excess glucose. Depolarization of hippocampal tissue with high K+ significantly increased the rate of oxidative phosphorylation, which was accompanied by a transient decrease in extracellular lactate concentration. Both effects were reverted by inhibition of the neuronal lactate transporter, monocarboxylate transporters 2 (MCT2), supporting the concept of an inward flux of lactate to neurons to fuel oxidative metabolism. We conclude that astrocytes are the main source of extracellular lactate which is used by neurons to fuel oxidative metabolism, both under resting and stimulated conditions.

Enriching and Smart Releasing Curcumin via Phenylboronic Acid‐Anchored Bioinspired Hydrogel for Diabetic Wound Healing

Diabetic wounds suffer from bacterial infections, reactive oxygen species, and inflammatory reactions. Curcumin (Cur) is a natural diketone with antibacterial, anti‐inflammatory, antioxidant activities, but poor water solubility and toxicity at high local concentration. Herein, inspired by the oxygen transport process of red blood cells via the dynamic interaction of hemoglobin and oxygen, phenylboronic acid (PBA)‐anchored hydrogel (GOHA‐PBA) is utilized to achieve active enrichment and smart release of Cur, which can reverse the inflammatory microenvironment and promote wound healing. First, PBA‐modified gelatin (Gel‐PBA) and oxidized hyaluronic acid (OHA) crosslink and form GOHA‐PBA by borate ester reaction and Schiff base reaction. GOHA‐PBA possesses excellent curcumin loading efficiency with 130 000 times than that in water and forms Cur‐laden GOHA‐PBA (GOHA‐Cur). GOHA‐Cur has injectability, self‐healing, and self‐adaptive properties, which are conducive to surgical procedure. GOHA‐Cur owns reversible adhesion properties, facilitating it be peeled off and remove harmful substances, including excess glucose, acids, bacteria, and ROS at the wounds. GOHA‐Cur can pH and glucose responsively release Cur; hence, it shows excellent antibacterial, antioxidant, anti‐inflammatory effects in vitro. Animal experiments show that GOHA‐Cur can inhibit inflammation and promote wound regeneration. This study can provide a valuable concept for Cur delivery and diabetic wound healing.

The role of ChREBP in carbohydrate sensing and NAFLD development.

Excessive sugar consumption and defective glucose sensing by hepatocytes contribute to the development of metabolic diseases including type 2 diabetes mellitus (T2DM) and nonalcoholic fatty liver disease (NAFLD). Hepatic metabolism of carbohydrates into lipids is largely dependent on the carbohydrate-responsive element binding protein (ChREBP), a transcription factor that senses intracellular carbohydrates and activates many different target genes, through the activation of de novo lipogenesis (DNL). This process is crucial for the storage of energy as triglycerides in hepatocytes. Furthermore, ChREBP and its downstream targets represent promising targets for the development of therapies for the treatment of NAFLD and T2DM. Although lipogenic inhibitors (for example, inhibitors of fatty acid synthase, acetyl-CoA carboxylase or ATP citrate lyase) are currently under investigation, targeting lipogenesis remains a topic of discussion for NAFLD treatment. In this Review, we discuss mechanisms that regulate ChREBP activity in a tissue-specific manner and their respective roles in controlling DNL and beyond. We also provide in-depth discussion of the roles of ChREBP in the onset and progression of NAFLD and consider emerging targets for NAFLD therapeutics.

Effect of electrical stimulation on the content of pAkt in myocyte cell culture under hyperglycemia

Introduction. The problems of studying the molecular mechanisms of pathogenesis, insulin resistance and finding new ways to correct them are still relevant.Aim: To study the effect of electrical stimulation on the amount of pAkt in a cell culture of C2C12 mouse myoblasts cultivated under hyperglycemic conditions.Material and Methods. We studied the effect of electrical stimulation on the amount of pAkt in a cell culture of C2C12 mouse myoblasts cultivated under hyperglycemic conditions. Cells were cultured in a medium containing 25 mM glucose and subjected to electrical impulse stimulation for 2, 6, and 24 hours.Results. It has been shown that the cultivation of C2C12 myoblasts in a medium with excess glucose is accompanied by a decrease in the amount of pAkt in cells, while pulsed electrical stimulation from 2 to 6 hours increases the concentration of this enzyme and restores the sensitivity of its phosphorylation pathways to insulin.Conclusions. The results obtained suggest that the contractile activity of muscle cells contributes to the restoration of cell sensitivity to insulin and the ability to absorb glucose, using the same regulatory and transport pathways that are affected i the development of type 2 diabetes.