The liver and glucose homeostasis

Question 1

What are the three main body fuels used for energy production?

Answer 1

The three main body fuels used for energy production are glucose (stored as glycogen), long chain fatty acids (stored as triacylglycerol), and amino acids (mainly present in proteins).

Question 2

Why is it necessary to store and release fuels in a controlled manner?

Answer 2

It is necessary to store fuels when they are abundant and release them in a controlled way during the post-absorptive period, exercise, or other periods of increased demand (e.g., illness or starvation).

Question 3

What happens to dietary compounds immediately after a meal?

Answer 3

After a meal, the immediate fate of dietary compounds involves the uptake of materials by the liver and adipose tissue, mainly through import processes.

Question 4

What happens during the post-absorptive period between meals?

Answer 4

During the post-absorptive period between meals, the cells of the liver and adipose tissues export materials.

Question 5

What is the role of glycogen mobilization?

Answer 5

Glycogen reserves are mobilized to maintain the availability of nutrients in the blood during the post-absorptive period.

Question 6

What is the major energy source for tissues?

Answer 6

Glucose is the major energy source for tissues.

Question 7

Where are excess carbohydrates stored?

Answer 7

Excess carbohydrates are stored as fat in adipose tissue and as glycogen in the liver.

Question 8

What is the function of the liver in relation to ketone bodies?

Answer 8

The liver synthesizes ketone bodies but cannot utilize them as an energy source. It does not oxidize ketone bodies.

Question 9

Name three types of ketone bodies.

Answer 9

The three types of ketone bodies are acetoacetate, beta-hydroxybutyrate, and acetone. They are produced from fatty acid breakdown.

Question 10

Why is blood glucose constantly replenished?

Answer 10

Glucose is a major energy substrate in the body, and blood glucose is constantly replenished to prevent hypoglycemia (low blood sugar levels).

Question 11

Why is the brain particularly vulnerable to hypoglycemia?

Answer 11

The brain is most vulnerable to hypoglycemia because cerebral cells primarily derive their energy from the aerobic metabolism of glucose. They cannot store significant amounts of glucose or synthesize glucose, and they cannot metabolize substrates other than glucose or ketone bodies.

Question 12

What are the limitations of cerebral cells in extracting glucose from the extracellular fluids?

Answer 12

Cerebral cells cannot extract sufficient glucose for their needs from the extracellular fluids at low concentrations because glucose entry into the brain is not facilitated by hormones.

Question 13

Which hormones are involved in controlling blood glucose levels?

Answer 13

Blood glucose levels are increased by glucagon, catecholamines, cortisol, and growth hormone, while they are decreased by insulin.

Question 14

What is gluconeogenesis?

Answer 14

Gluconeogenesis is the process of synthesizing glucose in the liver and kidneys from non-carbohydrate precursors, such as amino acids, glycerol, and lactate.

Question 15

What is glycogenolysis?

Answer 15

Glycogenolysis refers to the mobilization of glycogen stores in the liver.

Question 16

What are the major pathways involved in maintaining plasma glucose levels?

Answer 16

The major pathways involved in maintaining plasma glucose levels are gluconeogenesis (glucose synthesis from non-carbohydrate precursors), glycogenolysis (mobilization of liver glycogen stores), glycogen and fat synthesis (conversion of glucose into glycogen and fat), and glycolysis (oxidation of glucose by peripheral tissues).

Question 17

What is the normal range for maintaining plasma glucose levels?

Answer 17

Plasma glucose is normally maintained between 6.0 – 7.8 mmol/L, despite varying amounts of glucose entering the body.

Question 18

What are the sources of blood glucose?

Answer 18

The sources of blood glucose include glucose absorbed from the intestine for 2-3 hours following a meal.

Question 19

How long does glycogen degradation provide a source of blood glucose?

Answer 19

Glycogen degradation provides a source of blood glucose between meals and can last for 12-24 hours.

Question 20

What happens during sleep or extended food deprivation in terms of blood glucose?

Answer 20

During sleep or extended food deprivation, there is a gradual dependence on de novo glucose synthesis by gluconeogenesis.

Question 21

What are the hormonal controls of blood glucose homeostasis?

Answer 21

Blood glucose homeostasis is controlled by fluctuations in the circulating levels of insulin and glucagon. Alterations in the ratio of insulin to glucagon within the blood are essential for the maintenance of blood glucose.

Question 22

What are the steps involved in insulin secretion by pancreatic beta-cells?

Answer 22

When blood glucose is high, ATP levels in beta-cells increase.
This leads to the closure of K+ channels and membrane depolarization.
Depolarization causes voltage-gated Ca2+ channels to open, allowing Ca2+ to flow into the cell.
The increased intracellular Ca2+ concentration triggers insulin release through exocytosis.

Question 23

Why does blood glucose vary relatively little throughout the day or night despite changes in food intake?

Answer 23

Blood glucose remains relatively stable due to fluctuations in the circulating levels of insulin and glucagon, which help maintain blood glucose homeostasis.

Question 24

What condition demonstrates the importance of the insulin-to-glucagon ratio in maintaining blood glucose?

Answer 24

Diabetes mellitus demonstrates the importance of maintaining the appropriate ratio of insulin to glucagon for blood glucose regulation.

Question 25

What is the major and most important metabolic effect of insulin?

Answer 25

The major and most important metabolic effect of insulin is the stimulation of glucose entry into cells.

Question 26

How do polar molecules like glucose enter cells across a lipid membrane?

Answer 26

The transport of molecules like glucose across a lipid membrane can occur through passive or active transport systems.

Question 27

What is passive transport?

Answer 27

Passive transport is the movement of molecules across a membrane driven by a concentration gradient. Molecules move from an area of higher concentration to an area of lower concentration.

Question 28

What is active transport?

Answer 28

Active transport is the movement of molecules across a membrane against a concentration gradient. This process requires the expenditure of energy, often in the form of ATP.

Question 29

How do molecules enter cells via a concentration gradient?

Answer 29

Molecules enter cells via a concentration gradient during passive transport. They move from an area of higher concentration outside the cell to an area of lower concentration inside the cell.

Question 30

How do molecules enter cells against a concentration gradient?

Answer 30

Molecules enter cells against a concentration gradient during active transport. This process requires the use of transport proteins and the expenditure of energy to move molecules from an area of lower concentration to an area of higher concentration.

Question 31

What is the significance of glucose transport into tissues?

Answer 31

Glucose transport into tissues is essential as all cells express at least one transporter isoform and require a certain level of glucose uptake for their metabolic needs.

Question 32

Name the different glucose transporter isoforms and their associated tissues.

Answer 32

Glut 1: Found in many tissues, including erythrocytes, muscle, brain, kidney, colon, placenta, and fetal tissue.
Glut 2: Found in the liver and pancreatic beta cells.
Glut 3: Found in the brain.
Glut 4: Found in skeletal muscle and adipose tissue. It is insulin-sensitive.
Glut 5: Found in the small intestine and acts as a transporter for fructose, not glucose.

Question 33

How does glucose enter cells?

Answer 33

Glucose enters cells through facilitated diffusion, which is a carrier-mediated process. It enters the cells down its concentration gradient.

Question 34

What is the family of glucose transporter proteins called?

Answer 34

The family of glucose transporter proteins is called Gluts. These transporters are structurally related but are encoded by different genes and are expressed in a tissue-specific manner.

Question 35

How is glucose entry into tissues regulated by insulin?

Answer 35

Insulin regulates glucose entry into tissues through pathways involving PKC (protein kinase C) and Akt. Insulin stimulates the translocation of Glut 4 transporters to the plasma membrane, increasing glucose uptake by insulin-sensitive tissues.

Question 36

What additional factor increases glucose entry into working skeletal muscle?

Answer 36

Muscle contraction causes additional Glut 4 mobilization and translocation to the plasma membrane, leading to increased glucose entry into working skeletal muscle.

Question 37

What are the immediate effects of insulin?

Answer 37

The immediate effects of insulin include an increase in the rate of glucose uptake in muscle and adipocytes and modulation of the activity of enzymes involved in glucose metabolism. These effects occur within minutes and do not require protein synthesis. They occur at insulin concentrations of 10-9 to 10-10 mol/L.

Question 38

What are the longer-lasting effects of continuous exposure to insulin?

Answer 38

Continued exposure to insulin produces longer-lasting effects, including an increase in the expression of liver enzymes that synthesize glycogen and adipocyte enzymes that synthesize triacylglycerols. Insulin also inhibits lipolysis in adipose tissue by inactivating hormone-sensitive lipase, which mobilizes fatty acids from triglyceride stores. Additionally, insulin functions as a growth factor for some cells, such as fibroblasts. These effects occur over several hours and require continuous exposure to insulin at around 10-8 mol/L.

Question 39

What is the role of insulin in glucose metabolism?

Answer 39

Insulin increases the rate of glucose uptake in muscle and adipocytes, promoting glucose utilization. It also modulates the activity of enzymes involved in glucose metabolism. These immediate effects contribute to the regulation of blood glucose levels.

Question 40

How does insulin affect glycogen synthesis and lipid metabolism?

Answer 40

Insulin increases the expression of liver enzymes involved in glycogen synthesis, promoting the storage of glucose as glycogen. In adipocytes, insulin increases the expression of enzymes involved in triacylglycerol synthesis, promoting the storage of fatty acids as triacylglycerols. Insulin also inhibits lipolysis, preventing the breakdown of triglycerides into fatty acids.

Question 41

In addition to its metabolic effects, what other role does insulin play?

Answer 41

Insulin functions as a growth factor for some cells, such as fibroblasts, contributing to cell growth and proliferation.

Question 42

What are the two products of the pentose phosphate pathway?

Answer 42

The two products of the pentose phosphate pathway are ribose phosphate, which is used for the synthesis of RNA and DNA, and NADPH, which is used for biosynthesis and maintaining the redox balance of the cell.

Question 43

Where does the pentose phosphate pathway branch from in glycolysis?

Answer 43

The pentose phosphate pathway branches from glycolysis at glucose 6-phosphate.

Question 44

Which tissues are rich in pentose phosphate pathway enzymes?

Answer 44

Tissues involved in biosynthesis, such as the liver and adipose tissue, are rich in pentose phosphate pathway enzymes.

Question 45

What happens to pentose phosphate pathway intermediates in cells with less active biosynthetic processes?

Answer 45

In cells with less active biosynthetic processes, the intermediates of the pentose phosphate pathway, such as glyceraldehyde-3-phosphate and fructose-6-phosphate, are recycled back into glycolysis.

Question 46

What is the fate of glucose in muscle and heart cells?

Answer 46

In muscle and heart cells, glucose can be converted to pyruvate, which can further be converted to lactate or carbon dioxide (CO2) through oxidative metabolism. Glucose can also be used to produce energy or stored as glycogen. The heart and muscle cells have insulin-sensitive Glut4 transporters.

Question 47

What is the role of the insulin-sensitive Glut4 transporter in heart and muscle cells?

Answer 47

The insulin-sensitive Glut4 transporter in heart and muscle cells allows for the uptake of glucose from the bloodstream. Glucose can then be stored as glycogen or used to produce energy.

Question 48

What is the fate of glucose in the liver?

Answer 48

In the liver, glucose can be stored as glycogen or undergo glycolysis to form pyruvate, which can then be converted to lactate, carbon dioxide (CO2), or acetyl CoA. Some glucose is used to produce ATP, while excess acetyl CoA is used for fat synthesis. Additionally, a portion of glucose in the liver goes through the pentose phosphate pathway to form NADPH, which supports fat biosynthesis. The liver uses the Glut2 transport system.

Question 49

What is the fate of glucose in the brain?

Answer 49

In the brain, glucose is metabolized through aerobic metabolism to produce energy. It can also enter the pentose phosphate pathway to provide NADPH for lipid synthesis. Glucose uptake in the brain is facilitated by the Glut1 and Glut3 transport systems.

Question 50

What is the fate of glucose in adipose tissue?

Answer 50

In adipose tissue, glucose enters through the Glut4 transporter. It can be metabolized through glycolysis to produce acetyl CoA, which can be used to produce ATP or synthesize fats. Additionally, glucose can be used in the pentose phosphate pathway to produce NADPH, which is required for fatty acid synthesis.

Question 51

What is the fate of glucose in red blood cells (RBCs)?

Answer 51

In red blood cells, glucose is transported through the Glut1 transport system. It undergoes glycolysis to produce energy in the form of lactate. A portion of glucose also enters the pentose phosphate pathway to produce NADPH, which is essential for the maintenance of reduced glutathione. RBCs rely solely on glycolysis for energy production, as they lack mitochondria and cannot oxidize glucose fully via the TCA cycle and the electron transport chain.