Dopaminergic Regulation of Glucose-induced Insulin Secretion through Dopamine D2 Receptors in the Pancreatic Islets In Vitro

The stimulatory effect of dopamine through dopamine 1)2 receptor on glucose - induced insulin secretion was studied in the pancreatic islets in nitro. I)oparnilie signifieanlly stimula(ed insulin secretion at a concentration of 10 a N1 in the presence of high,glucose ( 20 nii1 ). ' fhe higher concentrations of dopamine (111 -1() 4) inhibited glucose- induced insulin secretion in the presence of both 4 mM1 and 20 m M glucose. Stimulatory and inhibitory effect of dopamine on glucose - induced insulin secretion was reverted by the addition of dopamine 1)2 receptor antagonists such as butaclamol and sulpiride . Norepinephrine (NE) at 111 4 11 concentration inhibited the dopamine uptake as well as its stimulatory effect at 11) - 8 IN1 concentration on glucose induced insulin secretion. Our results suggest that dopamine exerts a differential effect on glucose -induced insulin secretion through dopamine D2 receptor and it is essential for the regulation of glucose-induced insulin secretion by pancreatic islets.

Decreased GABAA Receptors Functional Regulation 3 in the Cerebral Cortex and Brainstem of Hypoxic Neonatal Rats: 4 Effect of Glucose and Oxygen Supplementation

Hypoxia in neonates can lead to biochemical and molecular alterations mediated through changes in neurotransmitters resulting in permanent damage to brain. In this study, we evaluated the changes in the receptor status of GABAA in the cerebral cortex and brainstem of hypoxic neonatal rats and hypoxic rats supplemented with glucose and oxygen using binding assays and gene expression of GABAAa1 and GABAAc5. In the cerebral cortex and brainstem of hypoxic neonatal rats, a significant decrease in GABAA receptors was observed, which accounts for the respiratory inhibition. Hypoxic rats sup- plemented with glucose alone and with glucose and oxygen showed, respectively, a reversal of the GABAA receptors, andGABAAa1 and GABAAc5 gene expression to control. Glucose acts as an immediate energy source thereby reducing the ATP-depletion-induced increase in GABA and oxygenation, which helps in encountering anoxia. Resuscitation with oxygen alone was less effective in reversing the receptor alterations. Thus, the results of this study suggest that reduction in the GABAA receptors functional regulation during hypoxia plays an important role in mediating the brain damage. Glucose alone and glucose and oxygen supplementation to hypoxic neonatal rats helps in protecting the brain from severe hypoxic damage.

Dopamine D1 and D2 Receptor Gene Expression and cGMP, IP3 and Ca2+ Regulation in the Brain Regions of Hypoxic Neonatal Rats: Role of Glucose, Oxygen and Epinephrine Supplementation

Department of Biotechnology, Cochin University of Science and Technology

GABA, serotonin, muscarinic receptors - their second messengers and transcription factors functional regulation in the brain regions of hypoxic neonatal rats: Resuscitation with glucose, oxygen and epinephrine

The present study was designed to investigate the protective effect of glucose, oxygen and epinephrine resuscitation on impairment in the functional role of GABAergic, serotonergic, muscarinic receptors, PLC, BAX, SOD, CAT and GPx expression in the brain regions of hypoxia induced neonatal rats. Also, the role of hormones - Triiodothyronine (T3) and insulin, second messengers – cAMP, cGMP and IP3 and transcription factors – HIF and CREB in the regulation of neonatal hypoxia and its resuscitation methods were studied. Behavioural studies were conducted to evaluate the motor function and cognitive deficit in one month old control and experimental rats. The efficient and timely supplementation of glucose plays a crucial role in correcting the molecular changes due to hypoxia, oxygen and epinephrine. The sequence of glucose, epinephrine and oxygen administration at the molecular level is an important aspect of the study. The additive neuronal damage effect due to oxygen and epinephrine treatment is another important observation. The corrective measures by initial supply of glucose to hypoxic neonatal rats showed from the molecular study when brought to practice will lead to healthy intellectual capacity during the later developmental stages, which has immense clinical significance in neonatal care.

Adrenergic and Glutamergic Receptor Gene Expression and Their Functional regulation in the Cerebral Cortex of Hypoxia Induced Neonatal Rats:Role of Oxygen,Epinephrine and Glucose Supplementation

In the present work, the role of oxygen, epinephrine and glucose supplementation in regulating neurotransmitter contents, adrenergic and glutamate receptor binding parameters in the cerebral cortex of experimental groups of neonatal rats were investigated. The study of neurotransmitters and their receptors in the cerebral cortex and the EEG pattern in the brain regions of neonatal rats were taken as index for brain damage due to hypoxia, oxygen and epinephrine. Real-Time PCR work was done to confirm the binding parameters. Second messenger, cyclic Adenosine Monophosphate (cAMP) was assayed to find the functional correlation of the receptors. Behavioural studies were carried out to confirm the biochemical and molecular studies. The efficient and timely supplementation of glucose plays a crucial role in correcting the molecular changes due to hypoxia, oxygen and epinephrine. The addictive neuronal damage effect due to oxygen and epinephrine treatment is another important observation. The corrective measures from the molecular study brought to practice will lead to maintain healthy intellectual capacity during the later developmental stages, which has immense clinical significance in neonatal care.

“Studies on glucose tolerant β-glucosidases from a novel Byssochlamys fulva and their applications in biomass to ethanol conversion”

Beta-glucosidases are critical enzymes in biomass hydrolysis process and is important in creating highly efficient enzyme cocktails for the bio-ethanol industry. Among the two strategies proposed for overcoming the glucose inhibition of commercial cellulases, one is to use heavy dose of BGL in the enzyme blends and the second is to do simultaneous saccharification and fermentation where glucose is converted to alcohol as soon as it is being generated. While the former needs extremely high quantities of enzyme, the latter is inefficient since the conditions for hydrolysis and fermentation are different. This makes the process technically challenging and also in this case, the alcohol generation is lesser, making its recovery difficult. A third option is to use glucose tolerant β-glucosidases which can work at elevated glucose concentrations. However, there are very few reports on such enzymes from microbial sources especially filamentous fungi which can be cultivated on cheap biomass as raw material. There has been very less number of studies directed at this, though there is every possibility that filamentous fungi that are efficient degraders of biomass may harbor such enzymes. The study therefore aimed at isolating a fungus capable of secreting glucose tolerant β- glucosidase enzyme. Production, characterization of β-glucosidases and application of BGL for bioethanol production were attempted.

Dopamine receptor subtypes functional regulation in insulin induced hypoglycemic neonatal rats: Effect of Glucose, Bacopa monnieri and Bacoside A resuscitation

In the present work we studied the potential of Bacopa monnieri and Bacoside A treatment to enhance the antioxidant system and support the neuronal survival in the hypoglycemic neonatal brain. For achieving the aim, DAD1 and DAD2 receptors functional regulation, gene expression of growth factors, neuronal survival and apoptotic factors during insulin induced hypoglycemic neonatal brain in rats were studied.

A Gain Scheduling Model Predictive Controller for Blood Glucose Control in Type 1 Diabetes

This paper presents a control strategy for blood glucose(BG) level regulation in type 1 diabetic patients. To design the controller, model-based predictive control scheme has been applied to a newly developed diabetic patient model. The controller is provided with a feedforward loop to improve meal compensation, a gain-scheduling scheme to account for different BG levels, and an asymmetric cost function to reduce hypoglycemic risk. A simulation environment that has been approved for testing of artificial pancreas control algorithms has been used to test the controller. The simulation results show a good controller performance in fasting conditions and meal disturbance rejection, and robustness against model–patient mismatch and errors in meal estimation

Prediction of glucose excursions under uncertain parameters and food intake in intensive insulin therapy for type 1 diabetes mellitus

Considering the difficulty in the insulin dosage selection and the problem of hyper- and hypoglycaemia episodes in type 1 diabetes, dosage-aid systems appear as tremendously helpful for these patients. A model-based approach to this problem must unavoidably consider uncertainty sources such as the large intra-patient variability and food intake. This work addresses the prediction of glycaemia for a given insulin therapy face to parametric and input uncertainty, by means of modal interval analysis. As result, a band containing all possible glucose excursions suffered by the patient for the given uncertainty is obtained. From it, a safer prediction of possible hyper- and hypoglycaemia episodes can be calculated

Prediction of postprandial blood glucose under intra-patient variability and uncertainty and its use in the design of insulin dosing strategies for type 1 diabetic patients

In this thesis I propose a novel method to estimate the dose and injection-to-meal time for low-risk intensive insulin therapy. This dosage-aid system uses an optimization algorithm to determine the insulin dose and injection-to-meal time that minimizes the risk of postprandial hyper- and hypoglycaemia in type 1 diabetic patients. To this end, the algorithm applies a methodology that quantifies the risk of experiencing different grades of hypo- or hyperglycaemia in the postprandial state induced by insulin therapy according to an individual patient’s parameters. This methodology is based on modal interval analysis (MIA). Applying MIA, the postprandial glucose level is predicted with consideration of intra-patient variability and other sources of uncertainty. A worst-case approach is then used to calculate the risk index. In this way, a safer prediction of possible hyper- and hypoglycaemic episodes induced by the insulin therapy tested can be calculated in terms of these uncertainties.

Biosensor-based diagnostics of contaminated groundwater: assessment and remediation strategy

Shallow groundwater beneath a former airfield site in southern England has been heavily contaminated with a wide range of chlorinated solvents. The feasibility of using bacterial biosensors to complement chemical analysis and enable cost-effective, and focussed sampling has been assessed as part of a site evaluation programme. Five different biosensors, three metabolic (Vibrio fischeri, Pseudomonas fluorescens 10568 and Escherichia coli HB101) and two catabolic (Pseudomonas putida TVA8 and E. coli DH5alpha), were employed to identify areas where the availability and toxicity of pollutants is of most immediate environmental concern. The biosensors used showed different sensitivities to each other and to the groundwater samples tested. There was generally a good agreement with chemical analyses. The potential efficacy of remediation strategies was explored by coupling sample manipulation to biosensor tests. Manipulation involved sparging and charcoal treatment procedures to simulate remediative engineering solutions. Sparging was sufficient at most locations. (C) 2004 Elsevier Ltd. All rights reserved.

Effect of dietary supplementation of different oils during the first or second half of pregnancy on the glucose tolerance of the sow

Poor glucose tolerance may be an under-researched contributory factor in the high (10% to 20%) pre-weaning mortality rate observed in pigs. Insulin resistance commences at around week 12 of gestation in the sow, although there are conflicting reports in the literature about the extent to which insulin resistance is modulated by maternal diet. The aim of the study was to determine the effects of supplementing the maternal diet with different dietary oils during either the first half or the second half of gestation on the glucose tolerance of the sow. Sows were offered the control (C: n = 5) diet as pellets or the C diet plus 10% extra energy (h = 16 per group) derived from either. (i) extra pellets; (ii) palm oil; (iii) olive oil; (iv) sunflower oil; or (v) fish oil. Experimental diets were fed during either the first (G1) or second (G2) half of gestation. A glucose tolerance test (GTT) was conducted on day 108 of gestation by administering 0.5g/kg glucose i.v. Blood samples were taken every 5 to 10 min for 90 min post administration. The change in body weight and backfat thickness during gestation was similar but both type and timing of dietary supplementation influenced litter size and weight. With the exception of the sunflower oil group, supplementing the maternal diet in G1 resulted in larger and heavier litters, particularly in mothers offered palm oil. Basal blood glucose concentrations tended to be more elevated in G1 than G2 groups, whilst plasma insulin concentrations were similar Following a GTT, the adjusted area under the curve was greater in G1 compared to G2 sows, despite no differences in glucose clearance. Maternal diet appeared to influence the relationship between glucose curve characteristics following a GTT and litter outcome. In conclusion, the degree of insulin sensitivity can be altered by both the period during which maternal nutritional supplementation is offered and the fatty acid profile of the diet.