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The Effect Of Antidiabetic Agent Glibenclamide And Meltformine On Lipids And Glycated Haemoglobin In Type 2 Diabetes Patient Attending Uith Ilorin
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2.4.1.1 BIOSYNTHESIS
Cholesterol is synthesized by virtually all tissues in humans, although liver, intestines, adrenal cortex and reproductive tissues, including ovaries, testes, and placenta, make the largest contributions to the body’s cholesterol pool. As with fatty acids, all the carbon atoms in cholesterol are provided by acetate, and NADPH provides the reducing equivalents. The pathway is endergonic, being driven by hydrolysis of the high-energy thioster bond of acetyl coenzymes A(CoA) and the terminal phosphate bond of adenosine triphosphate (ATP). Synthesis requires enzymes in both the cytosol and the membrane of the smooth endoplasmic reticulum (ER). The pathway is responsive to changes in cholesterol concentration, and regulatory mechanisms exist to balance the rate of cholesterol synthesis within the body against the rate of cholesterol excretion. An imbalance in this regulation can lead to an elevation in circulating levels of plasma cholesterol, with the potential for vascular disease (Prem, 2010).
• Synthesis of 3-hydroxy-3-methylglutaryl (HMG) CoA
The first two reactions in the cholesterol synthesis pathway are similar to those in the pathway that produce ketones bodies. They result in the production of HMG CoA. First, two acetyl CoA molecules condense to form acetoacetyl CoA. Next, a third molecule of acetyl CoA is added, producing HMG CoA, a six-carbon compound.
[Note: Liver parenchymal cells contains two isoenzymes of HMG CoA synthase. The cytosolic enzyme participates in cholesterol synthesis, whereas the mitochondria enzyme functions in the pathway for ketone body synthesis] (Prem, 2010).
• Synthesis of mevalonate
The next step, the reduction of HMG CoA to mevalonate, is catalysed by HMG CoA reductase and is the rate- limiting and key regulated step in cholesterol synthesis,. It occurs in the cytosol, uses two molecules of NADPH as the reducing agent, and releases CoA, making the reaction irreversible.
[Note: HMG CoA reductase is an intrinsic membrane protein of the Endoplasmic Reticulum, with the enzyme’s catalytic domain projecting into the cytosol (Prem, 2010).
• Synthesis of cholesterol
The reactions and enzymes involved in the synthesis of cholesterol from mevalonate are as follows;
• Mevalonate is converted to 5-pyrophosphomevalonate in two steps, each of which transfers a phosphate group from ATP.
• A five carbon isoprene unit – isopentyl pyrophosphate (IPP) – is formed by the decarboxylatrion of 5-pyrophosphomevalonate. The reaction requires ATP.
• IPP is isomerized to 3,3-dimethylally pyrophosphate (DPP).
• IPP and DPP condense to form ten-carbon geranyl pyrophosphate (GPP)
• A second molecule of IPP then condenses with GPP to form 15-carbon farnesyl pyrophosphate (FPP).
• Two molecules of FPP combine, releasing pyrophosphate, and are reduced, forming the 30-carbon compound squalene.
• Squalene is converted to the sterol lanosterol by a sequence of reactions catalysed by Endoplasmic Reticulum-associated enzymes that use molecular oxygen and NADPH. The hydroxylation of squalene triggers the cyclization of the structure to lanosterol.
• The conversion of lanosterol to cholestetrol is a multistep process, resulting in the shortening of the carbon 4, migration of the double bond from carbon 8 to carbon 5, and reduction of the double bond between carbon 24 and carbon 25 (Richard et al.,2012).
2.4.1.2 Regulation of Cholesterol Synthesis
Biosynthesis of cholesterol is directly regulated by the cholesterol levels present, though the homeostatic mechanisms involved are only partly understood. A higher intake from food leads to a net decrease in endogenous production, whereas lower intake from food has the opposite effect. The main regulatory mechanism is the sensing of intracellular cholesterol in the endoplasmic reticulum by the protein SREBP (sterol regulatory element-binding protein 1 and 2) (Rizos, 2011).
Cholesterol synthesis can also be turned off when cholesterol levels are high. HMG-CoA reductase contains both a cytosolic domain (responsible for its catalytic function) and a membrane domain. The membrane domain senses signals for its degradation. Increasing concentrations of cholesterol (and other sterols) cause a change in this domain's oligomerization state, which makes it more susceptible to destruction by the proteosome. This enzyme's activity can also be reduced by phosphorylation by an AMP-activated protein kinase. Because this kinase is activated by AMP, which is produced when ATP is hydrolyzed, it follows that cholesterol synthesis is halted when ATP levels are low (Rizos, 2011).
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ABSRACT - [ Total Page(s): 1 ]Abstract Is Coming Soon ... Continue reading---
APPENDIX A - [ Total Page(s): 1 ]APPENDIX IQUESTIONAIRE TO ACCESS THE ANTHROPOLOGIC INDICES OF PATIENTS WITH TYPE TWO DIABETES MELLITUS ON ANTIDIABETIC DRUGS (METFORMIN AND GLIBENCLAMIDE) ATTENDING UITH ILORIN.INTRODUCTION: I am a final year students of the Department of Medical Laboratory Science, School of Basic Medical Sciences, Kwara State University, Malete, Kwara State. This questionnaire is aimed at accessing the demographic indices of patients with type 2 Diabetes mellitus on metformin and diabinese in Ilorin metropolis ... Continue reading---
APPENDIX B - [ Total Page(s): 5 ]Step 2100µl of the supernatant was dispensed into the clean test tubes respectively.2ml of the cholesterol reagent was addedIt was incubated at room temperature for 10minsAbsorbance of sample against reagent blank was measured at 505nmGlycated HaemoglobinGlycated Haemoglobin is a form of haemoglobin that is measured primarily to identify the three-month average plasma glucose concentration. The test is limited to a three-month average.ProcedureReagentsBlank(µl) samp ... Continue reading---
CHAPTER ONE - [ Total Page(s): 2 ]The present study was designed to investigate and compare the effects of glibenclamide and metformin on prevalence of metabolic syndrome in type 2 diabetic patients.1.2 STATEMENT OF PROBLEMTo know if antidiabetic agents glibenclamide and meltformine has any effect on lipid and glycated haemoglobin in type 2 diabetes patients1.3 AIM OF STUDYTo evaluate the effect of antidiabetic agent glibenclamide and meltformine on lipids and glycated haemoglobin in type 2 diabetes patient attendi ... Continue reading---
CHAPTER THREE - [ Total Page(s): 1 ]CHAPTER THREE3.1 Material and Method3.2 Study AreaThe study was carried out at University of Ilorin Teaching Hospital, Ilorin, Kwara State. The hospital is located at the State capital of Ilorin, Kwara State Nigeria. It is a referral center to other public and private hospitals within and outside the state.3.3 SAMPLE SIZE DETERMINATIONThere was a random selection of ninety (90) subjects, 60 were type 2 Diabetes mellitus individual using either one or combine antidiabetic agent (glibe ... Continue reading---
CHAPTER FOUR - [ Total Page(s): 4 ]Tables 4.6: Correlation of Duration in Diabetes and BMI with biochemical parameters (T. cholesterol, High Density Lipoprotein, Low Density Lipoprotein, triglycerides, glycated, and fasting blood sugar) in Diabetic patient using antidiabetic drugs (Metformin and Glianpride). ... Continue reading---
CHAPTER FIVE - [ Total Page(s): 2 ]CHAPTER FIVE5.0 DISCUSSIONThe study shows discrepant results about the influence of metformin on lipid profile (10). Some studies, in agreement with ours, reported reduction only in TC levels (Grant, 1996; Ginsberg et al., 1999), while others reported reduction of TC and TG with an increase of HDL-C (Robinson et al., 1998; Yki-Jarvinen et al., 1999). Still other studies showed no changes in lipid profile (Groop et al., 1998; Rains et al., 1998). Another investigation showed an association of met ... Continue reading---
REFRENCES - [ Total Page(s): 3 ]Rodger, W. (2012). Sulphonylureas and heart disease in diabetes management. Diabetes Spectrum. Pg. 12–27.Rosenbaum, M. and Leibel, R. L. (2014). Role of leptin in energy homeostasis in humans. Journal of Endocrinology. 223(1): 83-96.Rowley, D.E. and Bezold, D.C. (2012). Using new insulin strategies in the outpatient treatment of diabetes: clinical applications. Journal of American Medical Association. Pg. 289.Shaw, D., De Rosa, N. and Di Maro, G. (2010). Metformin improves glucose, lipid ... Continue reading---
