Increase In Glucose Production Research Articles

Effect of oxymatrine on liver gluconeogenesis is associated with the regulation of PEPCK and G6Pase expression and AKT phosphorylation.

An increase in liver gluconeogenesis is an important pathological phenomenon in type 2 diabetes mellitus (T2DM) and oxymatrine is an effective natural drug used for T2DM treatment. The present study aimed to explore the effect of oxymatrine on gluconeogenesis and elucidate the underlying mechanism. Male Sprague-Dawley rats were treated with a high-fat diet and streptozotocin for 4 weeks to induce T2DM, and HepG2 cells were treated with 55 mM glucose to simulate T2DM in vitro. T2DM rats were treated with oxymatrine (10 or 20 mg/kg weight) or metformin for 4 weeks, and HepG2 cells were treated with oxymatrine (0.1 or 1 µM), metformin (0.1 µM), or oxymatrine combined with MK-2206 (AKT inhibitor) for 24 h. Fasting blood glucose and insulin sensitivity of rats were measured to evaluate insulin resistance. Glucose production and uptake ability were measured to evaluate gluconeogenesis in HepG2 cells, and the expression of related genes was detected to explore the molecular mechanism. Additionally, the body weight, liver weight and liver index were measured and hematoxylin and eosin staining was performed to evaluate the effects of the disease. The fasting glucose levels of T2DM rats was 16.5 mmol/l, whereas in the control rats, it was 6.1 mmol/l. Decreased insulin sensitivity (K-value, 0.2), body weight loss (weight, 300 g), liver weight gain, liver index increase (value, 48) and morphological changes were observed in T2DM rats, accompanied by reduced AKT phosphorylation, and upregulated expression of phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6Pase). High-glucose treatment significantly increased glucose production and decreased glucose uptake in HepG2 cells, concomitant with a decrease in AKT phosphorylation and increase of PEPCK and G6Pase expression. In vivo, oxymatrine dose-dependently increased the sensitivity of T2DM rats to insulin, increased AKT phosphorylation and decreased PEPCK and G6Pase expression in the liver, and reversed the liver morphological changes. In vitro, oxymatrine dose-dependently increased AKT phosphorylation and glucose uptake of HepG2 cells subjected to high-glucose treatment, which was accompanied by inhibition of the expression of the gluconeogenesis-related genes, PEPCK and G6Pase. MK-2206 significantly inhibited the protective effects of oxymatrine in high-glucose-treated cells. These data indicated that oxymatrine can effectively prevent insulin resistance and gluconeogenesis, and its mechanism may be at least partly associated with the regulation of PEPCK and G6Pase expression and AKT phosphorylation in the liver.

Hyperglycemia and stress response in acute coronary syndromes

Abstract Funding Acknowledgements Type of funding sources: Public hospital(s). Main funding source(s): University of Buenos Aires Background Cortisol is a stress marker in patients with acute coronary syndrome (ACS) and it has a permissive effect on the actions of hormones that increase glucose production. Its association with blood glucose levels in diabetic and non-diabetic patients could help to understand the relationship between stress, hyperglycaemia and mortality. Methods Prospective and observational single-centre study. All patients admitted with a diagnosis of ACS to the coronary care unit of a University Hospital were included. The age, sex and clinical characteristics were recorded, along with the clinical outcomes. On admission, blood samples were obtained to measure serum glucose (SG) and cortisol (SC). Results Over a total of 149 patients, 35.37% had a diagnosis of ST-segment elevation ACS. Median age was 69 (60.1 – 79) years, 61.1% were male, 59.5% were hypertense, 18.2% dyslipidemic, 23% smokers, and 28.4% diabetics. Total mortality during hospitalization was 6.8%, and cardiovascular mortality was 6.1%. We observed a significantly higher SC and SG on admission in patients who died (table 1), with a mild and positive correlation between them (Spearman’s rho = 0.24, p = 0.005). Diabetic patients had a higher SG on admission [191.1 mg/dl (157.5 – 250,8) vs. 116.0 mg/dl (99.0 – 141.0), < 0.001]. Diabetes was not associated with mortality, although correlation between glucose and cortisol remained constant in diabetics and non-diabetics (figure 1). Conclusion Hypercortisolemia and hyperglycaemia were associated with an increased in-hospital mortality. Although hyperglycemia confers a worse prognosis, we found that its correlation with cortisol was constant in diabetics and non-diabetics. This suggests that hyperglycaemia could be a surrogate stress marker, not related to diabetes as a risk factor in an acute setting. Serum glucose and cortisol on admission LaboratorySurvivorsNon-survivorsp-valueGlucose (mg/dL)128 (101 - 163)156 (134.5 - 197.2)0.04Cortisol (ug/dL)13.7 (7,98 - 23.65)43.7 (34.6 - 50.0)0.0004Abstract Figure. Serum cortisol and glucose on admission.

Factors responsible for low serum vitamin-D levels in type-2 diabetes mellitus females: a cross-sectional study

Background: Diabetes mellitus are a group of disorders as a result of reduced insulin secretion, insulin resistance, and increased glucose production and many more unknown etiologies. As compared to diabetic non-obese, diabetic obese individuals have an increased chance of 13.5 % in developing diabetic complications. Many diabetic patients are found to be vitamin-D deficient and its role in insulin regulation is being studied in many studies. Thus, diabetic complications and vitamin-D deficiency are likely to be developed in obese diabetic females.Methods: Type-2 diabetic females from 30 years to 60 years, attending in medicine as out-patient and female type-2 diabetes patients admitted in medical ward of RRMCH were assessed clinically. Parameters such as anthropometric measurements, weight, height, waist-hip ratio, tested for serum levels vitamin-D including other relevant investigations related to diabetes were done. Totally, 156 patients were assessed.Results: Assessment of 156 patients are as follows, 48.47±9.56years was the mean age of this study group. SD: 5.10±4.36 years is the mean diabetic duration of this study population. 0.98 was the mean waist-hip ratio. 98.93 cm was the mean waist circumference. 24.97 was the mean BMI. Mean fasting blood sugar (FBS) and post-prandial glucose test (PPBS) were: 202.73 mg/dl, 280.99 mg/dl respectively, 9.33% was the mean HbA1C. Majority of the females with type-2 diabetes (92.5%) had low levels of serum vitamin-D. 16.19 ng/ml was the mean serum vitamin-D levels. lower levels of serum vitamin-D were significantly associated with diabetic duration (p=0.082+), poor glycaemic control (p<0.001**) and increased BMI (p=0.011*).Conclusions: Majority of the females with type-2 diabetes mellitus were with waist-hip ratio more than 0.8 and Waist circumference more than 80 cm. Most of the study population had poor diabetic control. Lower levels of serum vitamin-D were found in almost all females with type-2 diabetes mellitus (92.5 %) and the most likely risk factor being obesity and poor glycaemic control as a conclusion of this study.

Perfluorooctanesulfonic Acid (PFOS) Thwarts the Beneficial Effects of Calorie Restriction and Metformin.

A combination of calorie restriction (CR), dietary modification, and exercise is the recommended therapy to reverse obesity and nonalcoholic fatty liver disease. In the liver, CR shifts hepatic metabolism from lipid storage to lipid utilization pathways, such as AMP-activated protein kinase (AMPK). Perfluorooctanesulfonic acid (PFOS), a fluorosurfactant previously used in stain repellents and anti-stick materials, can increase hepatic lipids in mice following relatively low-dose exposures. To test the hypothesis that PFOS administration interferes with CR, adult male C57BL/6N mice were fed ad libitum or a 25% reduced calorie diet concomitant with either vehicle (water) or 100 μg PFOS/kg/day via oral gavage for 6 weeks. CR alone improved hepatic lipids and glucose tolerance. PFOS did not significantly alter CR-induced weight loss, white adipose tissue mass, or liver weight over 6 weeks. However, PFOS increased hepatic triglyceride accumulation, in both mice fed ad libitum and subjected to CR. This was associated with decreased phosphorylated AMPK expression in liver. Glucagon (100 nM) treatment induced glucose production in hepatocytes, which was further upregulated with PFOS (2.5 μM) co-treatment. Next, to explore whether the observed changes were related to AMPK signaling, HepG2 cells were treated with metformin or AICAR alone or in combination with PFOS (25 μM). PFOS interfered with glucose-lowering effects of metformin, and AICAR treatment partially impaired PFOS-induced increase in glucose production. In 3T3-L1 adipocytes, metformin was less effective with PFOS co-treatment. Overall, PFOS administration disrupted hepatic lipid and glucose homeostasis and interfered with beneficial glucose-lowering effects of CR and metformin.

Impaired Pancreatic β-Cell Function in Critically Ill Children.

Critical illness hyperglycemia (CIH) is common in the pediatric intensive care unit (PICU). Increased glucose production, insulin resistance (IR), and pancreatic β-cell dysfunction are responsible mechanisms. We aimed to investigate β-cell function in the PICU and to uncover its relation to clinical and laboratory variables and ICU mortality. We prospectively recruited 91 children. Pancreatic β-cell function was assessed by using a homeostasis model assessment (HOMA)-β. Patients with β-cell function <40.0% had significantly higher Pediatric Risk of Mortality III (PRISM III) scores, higher rates of a positive C-reactive protein (CRP), lower IR, and a longer hospital stay. The patients with 40–80% β-cell function had the highest IR. Intermediate IR was found when the β-cell function was >80%. ICU survivors had better β-cell function than ICU non-survivors. A multivariate logistic regression analysis revealed that higher PRISM III score and HOMA-β <80.0% were significant predictors of mortality. In conclusion, β-cell dysfunction is prevalent among PICU patients and influences patient morbidity and mortality.

Adipose tissue and age‑dependent insulin resistance: New insights into WAT browning (Review).

Insulin resistance (IR) is defined as impaired insulin function, reduced glucose uptake and increased glucose production, which can result in type II diabetes, metabolic syndrome and even bone metabolic disorders. A possible reason for the increasing incidence of IR is population aging. Adipose tissue (AT) is an important endocrine organ that serves a crucial role in whole-body energy homeostasis. AT can be divided into white AT (WAT), beige AT and brown AT (BAT). Several mechanisms have been previously associated with age-dependent IR in WAT. However, BAT, a metabolically active tissue, controls the levels of plasma glucose and triglyceride metabolism. Therefore, the present review aimed to summarize the mechanisms of age-dependent IR induced by AT and to determine the role of WAT browning in achieving positive therapeutic outcomes in age-dependent IR.

EL TRATAMIENTO CON SOFOSBUVIR MEJORA LA RESISTENCIA A LA INSULINA INDUCIDA POR EL VIRUS DE LA HEPATITIS C

Chronic hepatitis C virus (HCV) infection is associated with insulin resistance and type 2 diabetes. The overall aim of this study was to evaluate the effects of sofosbuvir (SOF) on HCV-induced insulin resistance. Clinical parameters were recorded and insulin resistance index (HOMA) calculated from 42 insulin-resistant HCV-patients who underwent SOF-based regimens, at baseline, at the end of treatment (EoT), and at one year after the EoT. Likewise, Huh7 cells expressing full-length HCV replicons were used to elucidate the molecular mechanisms involved in insulin action regulated by SOF. All patients reached a sustained virological response after SOF treatment and, as expected, a significant reduction in liver damage markers and fibrosis stage was observed at the EoT that remained one year later. HOMA significantly improved throughout the study time period. Besides, an increase of total cholesterol, low-density lipoprotein cholesterol and apolipoprotein B levels were maintained over time after the EoT. At the molecular level, SOF treatment improved the activation of the insulin signalling cascade after stimulation with the hormone in HCV-hepatocytes and, accordingly, reversed the elevated expression of gluconeogenic genes, the increased glucose production and the impairment of glycogen synthesis induced by HCV. Furthermore, SOF challenge induced an increase of insulin receptor substrate 1 (IRS1) content parallel to a reduction in its serine phosphorylation in HCV-hepatocytes. These results provide novel evidence about the molecular mechanisms involved in the hepatic insulin sensitization induced by SOF treatment involving the recovery of IRS1 protein levels as a hallmark of SOF effects.

Role of Vidangadi Kwatha in Madhumeha (Diabetes Mellitus Type II)

Diabetes mellitus (DM) refers to a group of common metabolic disorders that share the phenotype of hyperglycaemia. The two broad categories of DM are designed type 1 and type 2. Type 1 diabetes is the result of complete or near-total insulin deficiency. Type 2 DM is a heterogeneous group of disorders characterized by variable degrees of insulin resis-tance, impaired insulin secretion, and increased glucose production. Here a case of newly diagnosed type 2 diabetes mellitus in a patient who underwent 3 follow up of Vidangadi Kwatha delivered in 3 months is reported. After treatment, the patient’s fasting blood glucose and post plasma blood glucose levels, as well as haemoglobin A1C level, were decreased. Further-more, no adverse effects were observed. The finding in this clinical study are encouraging and provide evidence supporting the effectiveness of Vidangadi Kwatha in reducing type 2 diabetes melli-tus in a patient.

Resveratrol attenuates dapagliflozin-induced renal gluconeogenesis via activating the PI3K/Akt pathway and suppressing the FoxO1 pathway in type 2 diabetes.

Dapagliflozin alleviates hyperglycemia by increasing glycosuria, but it induces renal gluconeogenesis, thus neutralizing its efficacy. Resveratrol (Rsv), a natural polyphenolic chemical, improves insulin sensitivity in type 2 diabetes (T2D). Here, we investigated the regulatory effects and underlying mechanisms of Rsv on dapagliflozin-induced renal gluconeogenesis. Male ob/ob mice were given the vehicle (HF), dapagliflozin (1 mg kg-1), Rsv (10 mg kg-1), or dapagliflozin and Rsv combination for 10 weeks. Glucose metabolism was evaluated by glucose and pyruvate tolerance tests. HK-2 cells (human renal proximal tubule cells) were treated with dapagliflozin (1 μmol L-1) for 2 h and further incubated with Rsv (10 μmol L-1) for 12 h. The effects of Rsv on gluconeogenesis and insulin signaling were assessed. Dapagliflozin treatment increased glucose production in HK-2 cells and lowered blood glucose and induced gluconeogenesis in ob/ob mice. After Rsv treatment, the enhanced glucose production and gluconeogenesis were alleviated. The upregulated mRNA and protein expression of phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6Pase) and the activation of the forkhead transcription factor O1 (FoxO1) protein in the dapagliflozin group were attenuated by Rsv administration. Rsv also improved renal insulin signaling by increasing PI3K and Akt phosphorylation. The PI3K inhibitor LY294002 dramatically decreased the p-Akt expression and activated FoxO1 by dephosphorylation, thus diminishing the inhibitory effects of Rsv on dapagliflozin-induced PEPCK and G6Pase expression. The data showed the mechanisms of Rsv in attenuating dapagliflozin-induced renal gluconeogenesis via activating the PI3K/Akt pathway and further suppressing FoxO1 activation, suggesting a potential intervention to achieve better glucose-lowering effects for SGLT2 inhibitors in T2D therapy.

Effect of elevated iron stores on lipid profile in patients of type 2 diabetes mellitus

Introduction: Diabetes Mellitus (DM) comprises a group of metabolic disorders presenting with hyperglycemia resulting from insulin deficiency or decreased glucose utilization and increased glucose production. Ferritin is a globular protein which is an index for iron stores present in the body. Many research studies have found relationship between elevated ferritin levels (iron stores) and the development of diabetes mellitus and metabolic syndrome. The present study was done to establish relationship between type 2 diabetes and ferritin levels and to see the effect of elevated iron stores on lipid profile i.e. total cholesterol, triglycerides, HDL (High density lipoprotein) and LDL (low density lipoprotein). Materials and Methods: 50 cases (patients of type 2 diabetes) and 50 apparently healthy subjects were selected and compared with each other. Serum ferritin, lipid profile i.e. total cholesterol, triglycerides, HDL and LDL were measured from serum at clinical biochemistry section. Results: Serum ferritin was high (p Conclusion: Study shows elevated ferritin level was found in the patients suffering from type 2 diabetes mellitus. Elevated iron stores are also associated with Total Cholesterol and Triglycerides. Keywords: Type 2 diabetes mellitus, Elevated iron stores, Ferritin, Lipid profile.

Altered glucose metabolism and insulin resistance in cancer-induced cachexia: a sweet poison.

Cancer cachexia is a wasting disorder characterised by specific skeletal muscle and adipose tissue loss. Cancer cachexia is also driven by inflammation, altered metabolic changes such as increased energy expenditure, elevated plasma glucose, insulin resistance and excess catabolism. In cachexia, host-tumor interaction causes release of the lactate and inflammatory cytokines. Lactate released by tumor cells takes part in hepatic glucose production with the help of gluconeogenic enzymes. Thus, Cori cycle between organs and cancerous cells contributes to increased glucose production and energy expenditure. A high amount of blood glucose leads to increased production of insulin. Overproduction of insulin causes inactivation of PI3K/Akt/m-TOR pathway and finally results in insulin resistance. Insulin is involved in maintaining the vitality of organs and regulate the metabolism of glucose, protein and lipids. Insulin insensitivity decreases the uptake of glucose in the organs and results in loss of skeletal muscles and adipose tissues. However, looking into the complexity of this metabolic syndrome, it is impossible to rely on a single variable to treat patients having cancer cachexia. Hence, it becomes greater a challenge to produce a clinically effective treatment for this metabolic syndrome. Thus, the present paper aims to provide an understanding of pathogenesis and mechanism underlining the altered glucose metabolism and insulin resistance and its contribution to the progression of skeletal muscle wasting and lipolysis, providing future direction of research to develop new pharmacological treatment in cancer cachexia.

High-level stable expression of gene for preparation of chlorothalonil hydrolytic dehalogenase and its application in elimination of chlorothalonil inhibition on bioconversion of lignocellulosic biomass

To achieve the high-level stable expression of chlorothalonil hydrolytic dehalogenase (Chd), the gene chd was first integrated into the chromosome of Bacillus subtilis WB800. High generation stability was achieved by almost no gene lost after six generations but Chd activity decreased. aprE promoter alteration, translation initiation region modification and multi-copy chromosome integration were studied and these modifications could increase Chd activity by 270%, 2304% and 25%. Chlorothalonil residual exhibited inhibition on bioconversion of lignocellulosic biomass. The addition of Chd crude enzyme (60μL per g wheat straw) could increase glucose production by 36.10% and 39.65% in synergistic hydrolysis and separate hydrolysis by laccase and cellulase with 120mg/L residual chlorothalonil. Filter paper activity and carboxymethyl cellulase activity were enhanced by 12.84% and 23.95%, and biomass of Trichoderma reesei was increased by 76.67% under 50μg chlorothalonil/g dry straw in solid-state fermentation. Thus, the high-level stable expressed Chd effectively eliminated chlorothalonil inhibition on enzymatic hydrolysis and solid-state fermentation. It showed promising potential for bioremediation of chlorothalonil pollution and improving conversion efficiency of lignocellulose.

Structural insights into differences in G protein activation by family A and family B GPCRs.

Family B heterotrimeric guanine nucleotide-binding protein (G protein)-coupled receptors (GPCRs) play important roles in carbohydrate metabolism. Recent structures of family B GPCR-Gs protein complexes reveal a disruption in the α-helix of transmembrane segment 6 (TM6) not observed in family A GPCRs. To investigate the functional impact of this structural difference, we compared the structure and function of the glucagon receptor (GCGR; family B) with the β2 adrenergic receptor (β2AR; family A). We determined the structure of the GCGR-Gs complex by means of cryo-electron microscopy at 3.1-angstrom resolution. This structure shows the distinct break in TM6. Guanosine triphosphate (GTP) turnover, guanosine diphosphate release, GTP binding, and G protein dissociation studies revealed much slower rates for G protein activation by the GCGR compared with the β2AR. Fluorescence and double electron-electron resonance studies suggest that this difference is due to the inability of agonist alone to induce a detectable outward movement of the cytoplasmic end of TM6.

Impact of Juvenile Diabetes Long-Term Treatment upon Adolescents Physical Activities at Al Nasiriya Diabetic and Endocrinology Center

Introduction: Exercise has a positive effect on health, strength gain, weight control, social activity and self development, contribute to the development of healthy habits in adults, but can also cause hypoglycemia. The variety, weight and duration of administration can cause various hormones (insulin, glucagon, catecholamine glucocorticoid), mediated metabolism. when the administration of insulin derived from insulin and / or an increase in anti-regulatory hormones increase glucose production in the liver and damage glucose in skeletal muscles. Although potential hyperglycemia can scare patients and their families, recipient fear of hypoglycemia can be a serious problem for clinical attention. Objectives: To determine impact of juvenile diabetes long-term treatment upon adolescents’ physical activity and to discovery out the relationship between impact of long-term treatment with adolescents specific demographic data. Methodology: A descriptive study design was performed to determine the impact of juvenile diabetes long-treatment upon adolescent’s physical activity in Al Nasiriya diabetic and endocrinology center. The study had started from February 6th, 2019 to June 7th, 2019. Non – probability (accidental) sample of (100) adolescents were selected. Conclusion: The present study concludes that the greatest impact of long-term treatment of diabetes on the adolescents lifestyle was on physical activity; in addition the statistical test shows that the significant association between the adolescents’ physical activity and their age, socio-economic status.

Correlation between atherogenic factors in complicated and uncomplicated type 2 diabetes mellitus

Background: Diabetes mellitus (DM) refers to a group of common metabolic disorders that share the phenotype of hyperglycemia. The factors contributing to hyperglycemia include reduced insulin secretion, decreased glucose utilization and increased glucose production. The vascular complications of DM are subdivided into microvascular (retinopathy, neuropathy, nephropathy) and macrovascular complications (coronary artery disease, peripheral vascular disease, cerebrovascular disease). There is an observed disparity between various vascular complications of diabetes and the atherogenic factors.Methods: The patients with type 2 diabetes mellitus attending outpatient and inpatient departments in Dr. B. R. Ambedkar Medical College and hospital, from September 2014 to September 2016 were selected for this study. All patients were subjected to detailed history, physical examination and laboratory investigations with respect to complications of diabetes mellitus.Results: In this study, 76% of the patients had poor glycemic control with elevated HbA1c &gt;7%. 38% of patients had normal BMI. 36% of patients were overweight and 26% were obese. 62% of patients were either overweight or obese. Hypercholesterolemia was seen in 26% of patients with poor glycemic control. Hyperhomocysteinemia was present in 38% of patients with microvascular complications and 33% of patients with macrovascular complications.Conclusions: Type 2 diabetes mellitus showed a strong correlation between glycemic status and incidence of diabetes complications. Hypercholesterolemia and hyperhomocysteinemia have added to the increased incidence of complications as additional factors in metabolic derangements as a consequence of poor glycemic control.

Characterization of Huh7 cells after the induction of insulin resistance and post-treatment with metformin.

Liver-specific insulin resistance is associated with the development of the main challenges in metabolism, resulting in dyslipidemia, hyperinsulinemia and hyperglycemia. In vitro models developed for researching hepatic insulin resistance are limited and employed cell lines without similar characteristics to primary human hepatocytes. The Huh7 cell line has been established as a model with similar characteristics to primary human hepatocytes. In addition, it has been identified in the Huh7 cell line that infection with the hepatitis C virus induces insulin resistance. Therefore, we analyzed the induction of insulin resistance (IR) in the Huh7 cell line using an overdosage of insulin and treatment with metformin for its reversal, with the purpose of establishing an insulin resistance model useful for metabolic and pharmacological studies. Insulin-resistant Huh7 (Huh7-IR) showed a reduction in Glut2, glycogen levels, and glucose uptake stimulated by insulin or tyrosine phosphorylation from the β-fraction of insulin receptor post-insulin stimulation, with an increase of glucose production and lipid intracellular content. These biomarkers are frequently observed in insulin-resistant hepatic cells. Moreover, treatment of Huh7-IR with 0.5, 1 or 2mM of metformin by 24h decreased the biomarkers associated with an insulin-resistant state. These results suggest that Huh7-IR could be used as an in vitro system to research hepatic insulin resistance in metabolic and pharmacological studies.

JARID1a Ablation in the Liver Alters Systemic Metabolism and Adaptation to Feeding

The liver is a key regulator of systemic energy homeostasis whose proper function is dependent on the circadian clock. Here, we show that livers deficient in the oscillator component JARID1a exhibit a dysregulation of genes involved in energy metabolism. Importantly, we find that mice that lack hepatic JARID1a have decreased lean body mass, decreased respiratory exchange ratios, faster production of ketones, and increased glucose production in response to fasting. Finally, we find that JARID1aloss compromises the response of the hepatic transcriptome to nutrient availability. In all, ablation of hepatic JARID1a disrupts the coordination of hepatic metabolic programs with whole-body consequences.

Maternal immunometabolic adaptation in pregnancy

Abstract Pregnant women undergo dynamic metabolic and immunologic changes to ensure provision of nutrients to, and prevent rejection of, the fetus. The mother increases glucose production, glucose intolerance and insulin resistance to support fetal-placental development and transitions from lipid storage to lipolysis to meet her own energy demands. Maternal immunoregulation prevents rejection of the fetal semi-allograft whilst maintaining protection against pathogens. Hypothesis Immunometabolic adaptation underpins maternal immune function changes in pregnancy. Aim To determine whether monocytes undergo metabolic adaptation in pregnancy and at which gestational stage this might occur. Results Peripheral blood monocytes of term pregnant (&amp;gt;37 weeks) and not pregnant women were compared using flow cytometry. Pregnant women had significantly more non-classical CD16+ monocytes, and CD16+ and CD16− subsets had more CD36 (fatty acid transporter; p = 0.0025) and less CD98 (amino acid transporter; p = 0.0043). Bioenergetic analysis of monocytes showed oxidative phosphorylation was significantly reduced in pregnant women; glycolysis was unchanged. Also, oxidative phosphorylation was reduced significantly in the mononuclear cells of women with gestational diabetes at 28 weeks compared to healthy pregnant women at the same gestational stage. Discussion Ongoing work includes analysis of mitochondrial health and measuring transcriptomics, biosynthetic lipids, cytokines, and enzyme responses. Results are vital to understanding immunological adaptation during pregnancy. This could provide insight into adverse pregnancy outcomes and women’s long-term health in relation to immune-mediated diseases.

ZnCl2 Enhanced Acid Hydrolysis of Pretreated Corncob for Glucose Production: Kinetics, Thermodynamics and Optimization Analysis

The biomass of agricultural wastes as a source of fermentable sugars for biofuels production will address the food security and environmental preservation issues. These wastes are rich in lignocellulosic materials which can be hydrolyzed into fermentable sugars. However, low sugar yield and high energy consumption are some of the challenges faced in the process of hydrolization. This study investigated the low-cost corncob substrate for glucose production by dilute sulphuric acid hydrolysis in the presence of ZnCl2 at temperatures below 100°C after pretreatment with 10% NaOH.Time dependent hydrolysis data were analyzed by Saeman model, and thermodynamic parameters were obtained using Erying and Arrhenius equations while Box-Behnken model (Design Expert 6.0 version) was used for experimental design. As the substrate concentration increased from 50 mg/L to 150 mg/L, glucose yield increased from 10.4 mg/g to 14.6 mg/g for pretreated corncob while an increase from 3.4 mg/g to 8.6 mg/g was noted for untreated corncob. The hydrolysis rate constant was two orders of magnitude higher than the degradation rate constant. Thermodynamic parameters revealed endothermic process with positive Gibb’s free energy of hydrolysis having average values of 84.76 kJ/mol and 79.87 kJ/mol for pretreated and untreated samples respectively. The optimum yield from the model was found to be 177.44 mg/g with 3.94% H2SO4 and 0.43 mol/L ZnCl2 for 200 g/L compared with optimum yield of 46.37 mg/g obtainable without ZnCl2. The results of this study showed that the alkaline pretreatment of corncob increased the accessibility of cellulose from the solid fraction and increased glucose production.

Oxidative stress in patients with diabetes mellitus type 2

Background: Diabetes mellitus (DM) refers to a group of common metabolic disorders that share the phenotype of hyperglycemia. Depending on the etiology of the DM, factors contributing to hyperglycemia include reduced insulin secretion, decreased glucose utilization, and increased glucose production. India is one of the epicenters of the global DM pandemic. Oxidative stress which is classically defined as an event resulting from the magnitude of imbalance between oxidant and antioxidant substances, generated in a setting of oxidation-reduction reactions, is hypothesized to play an important role in the development of DM. Aims and Objectives: This study aims to assess lipid peroxidation by estimating serum malondialdehyde (MDA) and antioxidant status by assaying paraoxonase-1 (PON-1) in Type 2 diabetes patients and healthy controls and also to study the correlation between MDA and PON-1 levels in patients with Type 2 diabetes. Materials and Methods: A cross-sectional comparative study was conducted in 152 participants, which were divided into two groups as patients with type 2 diabetes (n = 76) and control (n = 76) non-diabetic, healthy, age- and sex-matched individuals. The study was conducted in Government Medical College, Kozhikode, after the approval of the Institutional Ethical Committee. All the subjects who satisfied the inclusion and exclusion criteria and who gave informed consent were included in a consecutive manner till sample size is achieved. Serum MDA and PON-1 were estimated using spectrophotometry. The data were analyzed using Statistical Package for the Social Sciences (SPSS) version 18. Results: Oxidative stress was increased in type 2 diabetic patients as evidenced by significantly elevated MDA and reduced PON-1 than the normal controls. Conclusion: Oxidative stress is an important pathophysiological process for the development of type 2 diabetes. This study reveals the importance of screening all diabetes patients for oxidative stress. Dietary management and antioxidant supplementation would help them to prevent development of complications following diabetes, which, in turn, improve their quality of life.