TABLE OF CONTENTS

Title Page    –         –         –         –         –         –         –         –         i

Certification           –         –         –         –         –         –         –         ii

Dedication   –         –         –         –         –         –         –         –         iii

Acknowledgement           –         –         –         –         –         –         iv

Table of Contents  –         –         –         –         –         –         –         v

CHAPTER ONE: INTRODUCTION        –         –         –         1

CHAPTER TWO: THE LIVER       –         –         –         –         4

2.1     Function of the Liver-      –         –         –         –         –         –         5

2.1.1  Blood Supply-       –         –         –         –         –         –         –         6

2.1.2 Biliary Flow-         –         –         –         –         –         –         –         7

2.1.3 Metabolism  –        –         –         –         –         –         –         –         8

2.1.4 Breakdown of Insulin and Other Hormones- –         –         –         10

2.1.5 Lymph Production-         –         –         –         –         –         –         11

2.2     Clinical Significance of the Liver-       –         –         –         –         14

2.3     Glucose Metabolism-       –         –         –         –         –         –         18

2.3.1  Blood Glucose Regulation-        –         –         –         –         –         18

2.3.2  Mechanism of Glucose Metabolism –  –         –         –         –         20

CHAPTER THREE: THE ROLE OF

GLUCOSE IN THE METABOLISM OF GLUCOSE  –         21

3.1     Hepatic Glucose Production-     –         –         –         –         –         26

3.1.1 Gluconeogenesis-  –         –         –         –         –         –         –         26

3.1.2 Glycogenolysis-     –         –         –         –         –         –         –         30

3.1.3 Glucose Dephosphorylation-     –         –         –         –         –         31

3.2     The Use of Liver in Monitoring Glucose Disorder-           –         33

CHAPTER FOUR: SUMMARY AND CONCLUSION

4.1     Summary-    –         –         –         –         –         –         –         –         37

4.2     Conclusion – –         –         –         –         –         –         –         –         38

References

CHAPTER ONE: INTROUCTION

The liver is considered the second largest organ in the body and its weight ranges from 1.5 to 2.5% of the lean body weight. It preforms vascular, immunological, metabolic, and secretory and excretory functions (Mitra  and Metcalf, 2009). About 30% of the cardiac output is directed to the liver which exceptionally receives both arterial blood from the hepatic artery and venous blood from the portal vein the latter supplies about 70 to 75% of hepatic blood flow but only 50% of oxygen supply and it takes the blood directly from the gut to the liver. This allows for the first pass metabolism and makes the liver prone to the ingested drugs as they are absorbed from the intestine (Vaja and Ghuman, 2017). Its plays an essential role in metabolism and has an important role in preserving and regulating the level of lipid, glucose in the body as well as energy metabolism. Among the important functions performed by the liver is maintaining of blood glucose levels during fasting by releasing glucose from glycogen and synthesis of glucose from amino acids. Fat and cholesterols absorbed from diet were brought to and accumulate in the liver which produces fatty acids and cholesterols from acetyl-COA come from glucose. In the liver, excess fatty acids could be converted to ketone bodies that supply energy to brain and muscle in case of starvation (Chiang, 2014).

Understanding pathways of glucose metabolism in the liver of healthy humans may help to clarify metabolic alternation that occur in obesity and diabetes mellitus, two common diseases. In addition, glucose metabolism maybe involved in other disorders as well, as glucose provide reducing equivalents for fatty acid synthesis, ribose 5-phosphate for nucleotide synthesis and precursors for glycosylation reactions. Carbohydrate derived from intestinal absorption are initially handled by hepatocytes whereas dietary fatty acids form triglycerides inside the enterocytes and reach the lymph stream assembled as chylomicrons that are incorporated to the blood steam and finally arrive in the liver as remnant chylomicrons. In healthy individuals, the liver is a major site of glucose utilization during the post-prandial periods although hepatic contribution to glucose consumption relative to peripheral tissues has been found variable in different studies, from one-third to 50-60% of the glucose ingested. Peripheral glucose uptake including skeletal muscle and non-insulin sensitive tissues (predominantly the brain) account for the rest of total glucose disposal after meals (Ferrannini et al., 2000). To be utilized, glucose enters the hepatocyte and is phosphorylated to glucose 6-phosphate. Glucose 6-phosphate may follow a number of metabolic pathways, including glycogen synthesis, the hexosamine pathways, the pentose phosphate pathway and oxidative routes. Excess glucose is use to synthesize fatty acids in the liver. In addition to glucose utilization, human liver releases glucose to the systemic circulation, either from previously stored glycogen (glycogenolysis) or by generating glucose from precursors such as alanine, lactate and glycerol (gluconeogenesis). This unique ability of the human liver to store and release glucose is crucial to ensure periods of fasting.