Rate Of Glucose Production Research Articles

Evidence That in Uncontrolled Diabetes, Hyperglucagonemia Is Required for Ketosis but Not for Increased Hepatic Glucose Production or Hyperglycemia.

Several lines of evidence implicate excess glucagon secretion in the elevated rates of hepatic glucose production (HGP), hyperglycemia, and ketosis characteristic of uncontrolled insulin-deficient diabetes (uDM), but whether hyperglucagonemia is required for hyperglycemia in this setting is unknown. To address this question, adult male Wistar rats received either streptozotocin (STZ) to induce uDM (STZ-DM) or vehicle and remained nondiabetic. Four days later, animals received daily subcutaneous injections of either the synthetic GLP-1 receptor agonist liraglutide in a dose-escalating regimen to reverse hyperglucagonemia or its vehicle for 10 days. As expected, plasma glucagon levels were elevated in STZ-DM rats, and although liraglutide treatment lowered glucagon levels to those of nondiabetic controls, it failed to attenuate diabetic hyperglycemia, elevated rates of glucose appearance (Ra), or increased hepatic gluconeogenic gene expression. In contrast, it markedly reduced levels of both plasma ketone bodies and hepatic expression of the rate-limiting enzyme involved in ketone body production. To independently confirm this finding, in a separate study, treatment of STZ-DM rats with a glucagon-neutralizing antibody was sufficient to potently lower plasma ketone bodies but failed to normalize elevated levels of either blood glucose or Ra. These data suggest that in rats with uDM, hyperglucagonemia is required for ketosis but not for increased HGP or hyperglycemia.

Hepatocyte responses to in vitro freezing and β-adrenergic stimulation: Insights into the extreme freeze tolerance of subarctic Rana sylvatica.

The wood frog, Rana sylvatica LeConte 1825, is a freeze-tolerant amphibian widely distributed in North America. Subarctic populations of this species can survive experimental freezing to temperatures below -16 °C, whereas temperate populations tolerate freezing only at temperatures above -6 °C. We investigated whether hepatocytes isolated from frogs indigenous to Interior Alaska (subarctic) or southern Ohio (temperate) had distinct characteristics that could contribute to this variation in freeze tolerance capacity. Following in vitro freezing, cell damage, as assessed from lactate dehydrogenase leakage, was similar between samples from Alaskan and Ohioan frogs. Preincubation of cells in media containing glucose or urea, the two primary cryoprotectants used by R. sylvatica, markedly reduced freezing damage to hepatocytes; however, results suggested that cells of the northern phenotype were comparatively more amenable to cryoprotection by urea. Stimulation of isolated hepatocytes with β-adrenergic agonists, which simulates the freezing-induced cryoprotectant mobilization response, gave rates of glucose production from endogenous glycogen reserves that were similar between the populations. Our findings suggest that extreme freeze tolerance in subarctic R. sylvatica does not require an enhanced ability of the liver to resist freezing stress or rapidly mobilize cryoprotectant.

Glucose Homeostasis Disorders in Premature Infants

An abnormal plasma glucose concentration is one of the most commonly encounter­ ed metabolic problems in the intensive care of premature infants. Compared with term infants, glycogen reserves are lower in the preterm neonatal liver. Despite this, preterm infants are at a greater risk of hyperglycemia than term infants are, which is owing to comparable production rate of endogenous glucose and impaired ability to reduce glucose production rate in response to hyperglycemia. Debate continues about the normal plasma glucose concentrations and the guideline for glucose con­ trol in pre mature infants. Some randomized controlled trials in very low birth weight infants demonstrated little clinical benefit of tight glycemic control with early insulin therapy and higher calorie intake in terms of mortality, morbidities and growth para­ meters. Compared with term infants, preterm infants have limited endocrine and metabolic adaptation to hypoglycemia. In any case, hypoglycemia in premature in­ fants should not be considered a physiologic condition. The operational criteria for intervention of hypoglycemia should be different from that in term infants. Con­ tinuous non­invasive glucose monitoring is a promising tool considering the principle of minimal handling of extremely premature infants. However, the clinical implication of abnor mal glucose concentrations, previously undetected on intermittent measure­ ments, is unclear.

Cholesterol-Induced Hepatic Inflammation Does Not Underlie the Predisposition to Insulin Resistance in Dyslipidemic Female LDL Receptor Knockout Mice

Chronic inflammation is considered a causal risk factor predisposing to insulin resistance. However, evidence is accumulating that inflammation confined to the liver may not be causal to metabolic dysfunction. To investigate this, we assessed if hepatic inflammation explains the predisposition towards insulin resistance in low-density lipoprotein receptor knock-out (Ldlr −/−) mice. For this, wild type (WT) and Ldlr −/− mice were fed a chow diet, a high fat (HF) diet, or a high fat, high cholesterol (HFC) diet for 2 weeks. Plasma lipid levels were elevated in chow-fed Ldlr −/− mice compared to WT mice. Although short-term HF or HFC feeding did not result in body weight gain and adipose tissue inflammation, dyslipidemia was worsened in Ldlr −/− mice compared to WT mice. In addition, dyslipidemic HF-fed Ldlr −/− mice had a higher hepatic glucose production rate than HF-fed WT mice, while peripheral insulin resistance was unaffected. This suggests that HF-fed Ldlr −/− mice suffered from hepatic insulin resistance. While HFC-fed Ldlr −/− mice displayed the anticipated increased hepatic inflammation, this did neither exacerbate systemic nor hepatic insulin resistance. Therefore, our results show that hepatic insulin resistance is unrelated to cholesterol-induced hepatic inflammation in Ldlr −/− mice, indicating that hepatic inflammation may not contribute to metabolic dysfunction per se.

Pharmacokinetics and pharmacodynamics of insulin glargine given in the evening as compared with in the morning in type 2 diabetes.

To compare pharmacokinetics (PK) and pharmacodynamics (PD) of insulin glargine in type 2 diabetes mellitus (T2DM) after evening versus morning administration. Ten T2DM insulin-treated persons were studied during 24-h euglycemic glucose clamp, after glargine injection (0.4 units/kg s.c.), either in the evening (2200 h) or the morning (1000 h). The 24-h glucose infusion rate area under the curve (AUC0-24h) was similar in the evening and morning studies (1,058 ± 571 and 995 ± 691 mg/kg × 24 h, P = 0.503), but the first 12 h (AUC0-12h) was lower with evening versus morning glargine (357 ± 244 vs. 593 ± 374 mg/kg × 12 h, P = 0.004), whereas the opposite occurred for the second 12 h (AUC12-24h 700 ± 396 vs. 403 ± 343 mg/kg × 24 h, P = 0.002). The glucose infusion rate differences were totally accounted for by different rates of endogenous glucose production, not utilization. Plasma insulin and C-peptide levels did not differ in evening versus morning studies. Plasma glucagon levels (AUC0-24h 1,533 ± 656 vs. 1,120 ± 344 ng/L/h, P = 0.027) and lipolysis (free fatty acid AUC0-24h 7.5 ± 1.6 vs. 8.9 ± 1.9 mmol/L/h, P = 0.005; β-OH-butyrate AUC0-24h 6.8 ± 4.7 vs. 17.0 ± 11.9 mmol/L/h, P = 0.005; glycerol, P < 0.020) were overall more suppressed after evening versus morning glargine administration. The PD of insulin glargine differs depending on time of administration. With morning administration insulin activity is greater in the first 0-12 h, while with evening administration the activity is greater in the 12-24 h period following dosing. However, glargine PK and plasma C-peptide levels were similar, as well as glargine PD when analyzed by 24-h clock time independent of the time of administration. Thus, the results reflect the impact of circadian changes in insulin sensitivity in T2DM (lower in the night-early morning vs. afternoon hours) rather than glargine per se.

Coordinated changes in hepatic amino acid metabolism and endocrine signals support hepatic glucose production during fetal hypoglycemia.

Reduced fetal glucose supply, induced experimentally or as a result of placental insufficiency, produces an early activation of fetal glucose production. The mechanisms and substrates used to fuel this increased glucose production rate remain unknown. We hypothesized that in response to hypoglycemia, induced experimentally with maternal insulin infusion, the fetal liver would increase uptake of lactate and amino acids (AA), which would combine with hormonal signals to support hepatic glucose production. To test this hypothesis, metabolic studies were done in six late gestation fetal sheep to measure hepatic glucose and substrate flux before (basal) and after [days (d)1 and 4] the start of hypoglycemia. Maternal and fetal glucose concentrations decreased by 50% on d1 and d4 (P < 0.05). The liver transitioned from net glucose uptake (basal, 5.1 ± 1.5 μmol/min) to output by d4 (2.8 ± 1.4 μmol/min; P < 0.05 vs. basal). The [U-¹³C]glucose tracer molar percent excess ratio across the liver decreased over the same period (basal: 0.98 ± 0.01, vs. d4: 0.89 ± 0.01, P < 0.05). Total hepatic AA uptake, but not lactate or pyruvate uptake, increased by threefold on d1 (P < 0.05) and remained elevated throughout the study. This AA uptake was driven largely by decreased glutamate output and increased glycine uptake. Fetal plasma concentrations of insulin were 50% lower, while cortisol and glucagon concentrations increased 56 and 86% during hypoglycemia (P < 0.05 for basal vs. d4). Thus increased hepatic AA uptake, rather than pyruvate or lactate uptake, and decreased fetal plasma insulin and increased cortisol and glucagon concentrations occur simultaneously with increased fetal hepatic glucose output in response to fetal hypoglycemia.

Enzymatic degradation of Poly (ε-Caprolactone) and Starch blends bontaining SiO 2 nanoparticle by Amyloglucosidase and α-Amylase

The aims of the study were to investigate the effect of poly(e caprolactone) (PCL) and nano- SiO2 within the thermoplastic starch (TPS) blends on the rate and extent of starch enzymatic hydrolysis using enzymes α-amylase and amyloglucosidase. The results of this study have revealed that blends with nano-SiO2 content at 6 wt% exhibited a significantly reduced rate and extent of starch hydrolysis. The results suggest that this may have been attributed to interactions between starch and nano- SiO2 that further prevented enzymatic attack on the remaining starch phases within the blend. The total solids that remained after 6000 min were 52 wt. % (TPS: PCL); 59 wt.% (TPS: PCL: 2% nano-SiO2); 64 wt.% (TPS: PCL: 4% nano-SiO2); 67 wt.% (TPS: PCL: 6% nano-SiO2). The rate of glucose production from each nanocomposite substrates was most rapid for the substrate without nano- SiO2 and decreased with the addition of nano- SiO2, for TPS: PCL blend (374 μg/ml.h), 246 μg/ml.h (TPS: PCL: 2% nano- SiO2), 217 μg/ml.h (TPS: PCL: 4% nano- SiO2) and 199 μg/ml.h for (TPS: PCL: 6% nano- SiO2). Enzymatic degradation behaviour of TPS: PCL: nano- SiO2 was based on the determinations of Water resistance, Weight loss and the Reducing sugars.

Liver fat content and hepatic insulin sensitivity in overweight patients with type 1 diabetes.

Patients with type 1 diabetes mellitus (T1DM) lack the portal/peripheral insulin gradient, which might diminish insulin stimulation of hepatic lipogenesis and protect against development of nonalcoholic fatty liver disease (NAFLD). We compared liver fat content and insulin sensitivity of hepatic glucose production and lipolysis between overweight T1DM patients and nondiabetic subjects. We compared 32 overweight adult T1DM patients and 32 nondiabetic subjects matched for age, body mass index (BMI), and gender. Liver fat content was measured using proton magnetic resonance spectroscopy ((1)H-MRS), body composition by magnetic resonance imaging, and insulin sensitivity using the euglycemic-hyperinsulinemic clamp technique (insulin 0.4 mU/kg · min combined with infusion of D-[3-(3)H]glucose). We also hypothesized that low liver fat might protect from obesity-associated increases in insulin requirements and, therefore, determined insulin requirements across BMI categories in 3164 T1DM patients. Liver fat content was significantly lower in T1DM patients than in nondiabetic subjects (0.6% [25th-75th quartiles, 0.3%-1.1%] vs 9.0% [3.0%-18.0%]; P < .001). The endogenous rate of glucose production (R(a)) during euglycemic hyperinsulinemia was significantly lower (0.4 [-0.7 to 0.8] mg/kg fat-free mass · min vs 0.9 [0.2-1.6] fat-free mass · min; P = .012) and the percent suppression of endogenous Ra by insulin was significantly greater (89% [78%-112%] vs 77% [50%-94%]; p = .009) in T1DM patients than in nondiabetic subjects. Serum nonesterified fatty acid concentrations during euglycemic hyperinsulinemia were significantly lower (78.5 [33.0-155.0] vs 306 [200.0-438.0] μmol/L; P < .001) and the percent suppression of nonesterified fatty acids significantly higher (89.1% [78.6%-93.3%] vs 51.4% [36.5%-71.1%]; P < .001) in T1DM patients than in nondiabetic subjects. Insulin doses were similar across BMI categories. T1DM patients might be protected from steatosis and hepatic insulin resistance. Obesity may not increase insulin requirements in T1DM.

Absence of glucagon and insulin action reveals a role for the GLP-1 receptor in endogenous glucose production.

The absence of insulin results in oscillating hyperglycemia and ketoacidosis in type 1 diabetes. Remarkably, mice genetically deficient in the glucagon receptor (Gcgr) are refractory to the pathophysiological symptoms of insulin deficiency, and therefore, studies interrogating this unique model may uncover metabolic regulatory mechanisms that are independent of insulin. A significant feature of Gcgr-null mice is the high circulating concentrations of GLP-1. Hence, the objective of this report was to investigate potential noninsulinotropic roles of GLP-1 in mice where GCGR signaling is inactivated. For these studies, pancreatic β-cells were chemically destroyed by streptozotocin (STZ) in Gcgr(-/-):Glp-1r(-/-) mice and in Glp-1r(-/-) animals that were subsequently treated with a high-affinity GCGR antagonist antibody that recapitulates the physiological state of Gcgr ablation. Loss of GLP-1 action substantially worsened nonfasting glucose concentrations and glucose tolerance in mice deficient in, and undergoing pharmacological inhibition of, the GCGR. Further, lack of the Glp-1r in STZ-treated Gcgr(-/-) mice elevated rates of endogenous glucose production, likely accounting for the differences in glucose homeostasis. These results support the emerging hypothesis that non-β-cell actions of GLP-1 analogs may improve metabolic control in patients with insulinopenic diabetes.

Targeting steroid receptor coactivator 1 with antisense oligonucleotides increases insulin-stimulated skeletal muscle glucose uptake in chow-fed and high-fat-fed male rats.

The steroid receptor coactivator 1 (SRC1) regulates key metabolic pathways, including glucose homeostasis. SRC1(-/-) mice have decreased hepatic expression of gluconeogenic enzymes and a reduction in the rate of endogenous glucose production (EGP). We sought to determine whether decreasing hepatic and adipose SRC1 expression in normal adult rats would alter glucose homeostasis and insulin action. Regular chow-fed and high-fat-fed male Sprage-Dawley rats were treated with an antisense oligonucleotide (ASO) against SRC1 or a control ASO for 4 wk, followed by metabolic assessments. SRC1 ASO did not alter basal EGP or expression of gluconeogenic enzymes. Instead, SRC1 ASO increased insulin-stimulated whole body glucose disposal by ~30%, which was attributable largely to an increase in insulin-stimulated muscle glucose uptake. This was associated with an approximately sevenfold increase in adipose expression of lipocalin-type prostaglandin D2 synthase, a previously reported regulator of insulin sensitivity, and an approximately 70% increase in plasma PGD2 concentration. Muscle insulin signaling, AMPK activation, and tissue perfusion were unchanged. Although GLUT4 content was unchanged, SRC1 ASO increased the cleavage of tether-containing UBX domain for GLUT4, a regulator of GLUT4 translocation. These studies point to a novel role of adipose SRC1 as a regulator of insulin-stimulated muscle glucose uptake.

Increased and early lipolysis in children with long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) deficiency during fast.

Children with long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency (LCHAD) have a defect in the degradation of long-chain fatty acids and are at risk of hypoketotic hypoglycemia and insufficient energy production as well as accumulation of toxic fatty acid intermediates. Knowledge on substrate metabolism in children with LCHAD deficiency during fasting is limited. Treatment guidelines differ between centers, both as far as length of fasting periods and need for night feeds are concerned. To increase the understanding of fasting intolerance and improve treatment recommendations, children with LCHAD deficiency were investigated with stable isotope technique, microdialysis, and indirect calometry, in order to assess lipolysis and glucose production during 6 h of fasting. We found an early and increased lipolysis and accumulation of long chain acylcarnitines after 4 h of fasting, albeit no patients developed hypoglycemia. The rate of glycerol production, reflecting lipolysis, averaged 7.7 ± 1.6 µmol/kg/min, which is higher compared to that of peers. The rate of glucose production was normal for age; 19.6 ± 3.4 µmol/kg/min (3.5 ± 0.6 mg/kg/min). Resting energy expenditure was also normal, even though the respiratory quotient was increased indicating mainly glucose oxidation. The results show that lipolysis and accumulation of long chain acylcarnitines occurs before hypoglycemia in fasting children with LCHAD, which may indicate more limited fasting tolerance than previously suggested.

Glucose metabolism derangements in adults with the MELAS m.3243A>G mutation

The m.3243A>G mutation in the mitochondrial gene MT-TL1 leads to a wide clinical spectrum ranging from asymptomatic carriers to MELAS (mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes) at the severe end. Diabetes mellitus (DM) occurs in mitochondrial diseases, with the m.3243A>G mutation being the most common mutation associated with mitochondrial DM. The pathogenesis of mitochondrial DM remains largely unknown, with previous studies suggesting that impaired insulin secretion is the major factor. In this study we used stable isotope infusion techniques to assess glucose metabolism in vivo and under physiological conditions in 5 diabetic and 11 non-diabetic adults with the m.3243A>G mutation and 10 healthy adult controls. Our results revealed increased glucose production due to increased gluconeogenesis in both diabetic and non-diabetic subjects with the m.3243A>G mutation. In addition, diabetic subjects demonstrated insulin resistance and relative insulin deficiency, resulting in an inability to increase glucose oxidation which can explain the development of DM in these subjects. Non-diabetic subjects showed normal insulin sensitivity; and therefore, they were able to increase their glucose oxidation rate. The ability to increase glucose utilization can act as a compensatory mechanism that explains why these subjects do not have DM despite the higher rate of glucose production. These results suggest that increased gluconeogenesis is not enough to cause DM and the occurrence of combined insulin resistance and relative insulin deficiency are needed to develop DM in individuals with the m.3243A>G mutation. Therefore, multiple defects in insulin and glucose metabolism are required for DM to occur in individuals with mitochondrial diseases. The results of this study uncover previously undocumented alterations in glucose metabolism in individuals with the m.3243A>G mutation that contribute significantly to our understanding of the pathogenesis of mitochondrial DM and can have significant implications for its management.

Effects of delayed gastric emptying on postprandial glucose kinetics, insulin sensitivity, and β-cell function.

Controlling meal-related glucose excursions continues to be a therapeutic challenge in diabetes mellitus. Mechanistic reasons for this need to be understood better to develop appropriate therapies. To investigate delayed gastric emptying effects on postprandial glucose turnover, insulin sensitivity, and β-cell responsivity and function, as a feasibility study prior to studying patients with type 1 diabetes, we used the triple tracer technique C-peptide and oral minimal model approach in healthy subjects. A single dose of 30 μg of pramlintide administered at the start of a mixed meal was used to delay gastric emptying rates. With delayed gastric emptying rates, peak rate of meal glucose appearance was delayed, and rate of endogenous glucose production (EGP) was lower. C-peptide and oral minimal models enabled the assessments of β-cell function, insulin sensitivity, and β-cell responsivity simultaneously. Delayed gastric emptying induced by pramlintide improved total insulin sensitivity and decreased total β-cell responsivity. However, β-cell function as measured by total disposition index did not change. The improved whole body insulin sensitivity coupled with lower rate of appearance of EGP with delayed gastric emptying provides experimental proof of the importance of evaluating pramlintide in artificial endocrine pancreas approaches to reduce postprandial blood glucose variability in patients with type 1 diabetes.

Effect of eplerenone on insulin action in essential hypertension: a randomised, controlled, crossover study.

An association exists between hyperaldosteronism, hypertension and impaired insulin action. Eplerenone is a selective mineralocorticoid receptor antagonist; however, little is known about its effects on insulin action. The aim of this study was to determine the effect of eplerenone on insulin action in hypertensive adults, using the hyperinsulinaemic euglycaemic clamp. A randomised, controlled, double-blind, crossover design was employed. After a 6-week washout period, hypertensive, non-diabetic patients were treated with either eplerenone 25 mg twice daily or doxazosin 2 mg twice daily for 12 weeks. After each treatment period, insulin action was assessed by a hyperinsulinaemic euglycaemic clamp, with isotope dilution methodology. After washout, treatment groups were crossed over. Fifteen patients completed the study. There were no differences in fasting glucose, or fasting insulin between treatment with eplerenone or doxazosin. The measure of overall insulin sensitivity, exogenous glucose infusion rates during the last 30 min of the clamp, was similar with both treatments; 23.4 (3.9) μmol kg(-1) min(-1) after eplerenone and 23.3 (3.6) μmol kg(-1) min(-1) after doxazosin (P=0.83). Isotopically determined fasting endogenous glucose production rates were similar after both treatments (eplerenone 9.4 (0.6) μmol kg(-1) min(-1) vs doxazosin 10.6 (0.7) μmol kg(-1) min(-1)). There was a trend for lower endogenous glucose production rates during hyperinsulinaemia following eplerenone compared with doxazosin (2.0 (0.8) μmol kg(-1) min(-1) vs 4.1 (0.9) μmol kg(-1) min(-1)). There was no difference in insulin stimulated peripheral glucose utilisation rates after treatment with eplerenone or doxazosin (25.4 (3.6) μmol kg(-1) min(-1) vs 27.0 (3.9) μmol kg(-1) min(-1)). This study gives reassuring evidence of the neutral effect of eplerenone on insulin action in hypertensive, non-diabetic patients.

New liver-β-cell axis that controls insulin secretory capacity.

New liver-β-cell axis that controls insulin secretory capacity.

Abdominal subcutaneous adipose tissue insulin resistance and lipolysis in patients with non-alcoholic steatohepatitis.

BackgroundSystemic insulin resistance (IR) is a primary feature in non-alcoholic steatohepatitis (NASH), however, there remain limited data on tissue-specific insulin sensitivity in vivo.MethodsWe examined tissue-specific (adipose, muscle and liver) insulin sensitivity and inflammation in 16 European Caucasian patients with biopsy-confirmed NASH and in 15 healthy controls. All underwent a two-step hyperinsulinaemic euglycaemic clamp incorporating stable isotope measurements of carbohydrate and lipid metabolism with concomitant subcutaneous adipose tissue (SAT) microdialysis.ResultsHepatic and muscle insulin sensitivity were decreased in patients with NASH compared with controls, as demonstrated by reduced suppression of hepatic glucose production and glucose disposal (Gd) rates following insulin infusion. In addition, rates of lipolysis were higher in NASH patients with impaired insulin-mediated suppression of free fatty acid levels. At a tissue specific level, abdominal SAT in patients with NASH was severely insulin resistant, requiring >sixfold more insulin to cause ½-maximal suppression of glycerol release when compared with healthy controls. Furthermore, patients with NASH had significantly higher circulating levels of pro-inflammatory adipocytokines than controls.ConclusionNASH patients have profound IR in the liver, muscle and in particular adipose tissues. This study represents the first in vivo description of dysfunctional SAT in patients with NASH.

Enzymatic Hydrolysis of Rice Straw to Fermentable Sugar: Kinetic Study

As the gradual up-growing trend of industrialization and urbanization leading steady increment of demand of energy; eco-friendly, bio degradable, cost competitive and promising source of energy with high sustainability is toughly needed for the new era of modern world. Hydrolysis of cellulose by cellulase enzymes is a vital candidate for this option. It is a solid-liquid heterogeneous reaction; strongly affected by the non-reaction resistances caused most notably by the crystalline structure; reaction environment parameters as temperature, pH, characteristics of enzyme, cell &amp; substrate loading and hence must have to be defined for specific enzyme-substrate amalgamation. In this present investigation, glucose was produced from rice straw using cellulytic enzyme pseudomonas sp., isolated from municipal solid waste. Glucose yield was found to increase as the rice straw particle size decreased from 0.5 mm to 45 ?m, while the optimal temperature and pH were found within the range of 30°C and 7.0 respectively. The concentration and rate of glucose production was observed to depend on pretreatment of rice straw, substrate concentration and enzyme loading. A kinetic model rate expression has been developed for such a process based on the Michaelis – Mentens and Line weaver–Burk approach. Comparison between the experimental data and those predicted from the rate model indicate good agreement with a mean absolute deviation of about 0.304916. DOI: http://dx.doi.org/10.3329/jce.v27i2.17778 Journal of Chemical Engineering, IEB Vol. ChE. 27, No. 2, December 2012: 20-24

Fermentable Sugar Production and Separation from Water Hyacinth Using Enzymatic Hydrolysis

Water hyacinth containing a remarkable amount of cellulose which is found throughout the world as unusable material that can be used as one of the promising source for the production of glucose, initial step to produce bio ethanol. In this current study different types of treatments highest glucose concentration was obtained by hot water treated method. In addition, glucose was produced from water hyacinth using cellulytic enzyme pseudomonas sp., isolated from cow dung. Glucose concentration and production rate increases with the increasing of substrate concentration and enzyme loading, particle size 45µm and a pH 6.00 and temperature 40°C are the optimum for glucose production. A kinetic model rate expression has been developed for enzymatic hydrolysis of water hyacinth based on the Michaelis – Mentens model and parameters are determined. 0.15gm Reducing sugar are separated from the mixture of glucose water solution using 2 gm of water hyacinth. 0.531mg/l Cellulytic composition in water hyacinth are determined.

Pharmacokinetics, hemodynamic and metabolic effects of epinephrine to prevent post-operative low cardiac output syndrome in children

IntroductionThe response to exogenous epinephrine (Ep) is difficult to predict given the multitude of factors involved such as broad pharmacokinetic and pharmacodynamic between-subject variabilities, which may be more pronounced in children. We investigated the pharmacokinetics and pharmacodynamics of Ep, co-administered with milrinone, in children who underwent open heart surgical repair for congenital defects following cardiopulmonary bypass, including associated variability factors.MethodsThirty-nine children with a high risk of low cardiac output syndrome were prospectively enrolled. Ep pharmacokinetics, hemodynamic and metabolic effects were analyzed using the non-linear mixed effects modeling software MONOLIX. According to the final model, an Ep dosing simulation was suggested.ResultsEp dosing infusions ranged from 0.01 to 0.23 μg.kg-1.min-1 in children whose weight ranged from 2.5 to 58 kg. A one-compartment open model with linear elimination adequately described the Ep concentration-time courses. Bodyweight (BW) was the main covariate influencing clearance (CL) and endogenous Ep production rate (q0) via an allometric relationship: CL(BWi) = θCL x (BWi)3/4 and q0(BWi) = θq0 x (BWi )3/4. The increase in heart rate (HR) and mean arterial pressure (MAP) as a function of Ep concentration were well described using an Emax model. The effect of age was significant on HR and MAP basal level parameters. Assuming that Ep stimulated the production rate of plasma glucose, the increases in plasma glucose and lactate levels were well described by turnover models without any significant effect of age, BW or exogenous glucose supply.ConclusionsAccording to this population analysis, the developmental effects of BW and age explained a part of the pharmacokinetic and pharmacodynamics between-subject variabilities of Ep administration in critically ill children. This approach ultimately leads to a valuable Ep dosing simulation which should help clinicians to determine an appropriate a priori dosing regimen.

Short-Term Administration of Pegvisomant Improves Hepatic Insulin Sensitivity and Reduces Soleus Muscle Intramyocellular Lipid Content in Young Adults With Type 1 Diabetes

Data on the metabolic effects of GH derived from studies using GH suppression by pharmacological agents may not reflect selective actions. The purpose of this study was to evaluate the effects of GH antagonism on glucose and lipid metabolism using pegvisomant, a selective GH receptor antagonist in patients with type 1 diabetes (T1D). In a randomized, placebo-controlled, crossover study, 10 young adults with T1D were evaluated at baseline and after 4 weeks of treatment with either 10 mg of pegvisomant or placebo. The assessments included an overnight euglycemic steady state followed by a hyperinsulinemic euglycemic clamp and used glucose and glycerol cold stable isotopes. Hepatic and peripheral insulin sensitivity (IS), lipid turnover, and intramyocellular lipid (IMCL) were measured. Compared with placebo, pegvisomant treatment resulted in lower IGF-I levels (P < .001). During the overnight steady state, insulin requirements for euglycemia (P = .019), insulin levels (P = .008), and glucose production rates (Ra) (P = .033) were reduced. During the clamp study, glucose infusion rates (P = .031) increased and glucose Ra (P = .015) decreased whereas glucose disposal rates were unchanged. Free fatty acid levels were similar during the steady state but were lower during the clamp (P = .040) after pegvisomant. Soleus muscle IMCL decreased after treatment (P = .024); however, no change in tibialis anterior muscle was observed. The study demonstrates that GH antagonism in T1D results in improved hepatic insulin sensitivity. Lack of consistent changes in free fatty acid levels may suggest a direct effect of GH on IS. Unchanged peripheral IS despite reductions in IMCL indicate that GH-induced alterations in IMCL may not be causally linked to glucose metabolism.