PBL 6: Kylie Nicholls -Diabetes

Question 1

Identify conditions under which insulin and glucagon are released from the pancreas

Answer 1

Insulin release

1. Fed state
2. Increased in Blood Glucose concentration
3. Incretins -substances that promote insulin secretion
4. Sulfonylureas (drugs that stimulate beta cell activity)
5. Alpha adrenergic stimulation

Glucagon Release

1. Fasting State
2. Decreases in insulin secretion

Question 2

List the major roles of insulin in the body

Answer 2

Increases GLUT-4 translocation in adipose and muscle tissue -> increases uptake of glucose

Inhibits

1. HSL -> Decreased lipolysis
2. Protein breakdown to AAs
3. Glycogen breakdown
4. Gluconeogenesis
5. Glucagon Release

Stimulates

1. FA storage as TAGs
2. AA formation into proteins
3. Glycogen synthesis
4. Glycolysis

Question 3

List the major roles of glucagon in the body.

Answer 3

Inhibits

1. TAG synthesis from FAs
2. Protein synthesis from AAs
3. Glycogen Synthesis
4. Glycolysis

Stimulates

1. Protein breakdown and AA release
2. TAG breakdown and FA release
3. Glycogen breakdown and Glucose release
4. Gluconeogenesis

Question 4

Recognise the importance of maintaining blood glucose between meals

Answer 4

Importance of Blood Glucose Level

• Primary fuel source
• Required by the brain
• Lack of available glucose

Question 5

Describe the major controls in normal individuals exerted by insulin on glucose uptake into muscle cells.

Answer 5

Insulin:

1. Recruitment of GLUT4 transports to plasma membrane
2. Promotion of glycogen synthesis from glucose by enhancing transcription of hexokinase, PFK and pyruvate dehydrogenase
3. Promotion of protein synthesis
4. Inhibition of Protein Breakdown

Question 6

Describe the major controls in normal individuals exerted by insulin on glucose uptake into adipocytes.

Answer 6

1. Promotes glucose uptake by recruiting GLUT4 transporters to plasma membrane
2. Promotes glycolysis, leading to formation of a-glycerol phosphate and conversion of pyruvate to FFAs through pyruvate dehydrogenase
3. Promotes esterification of a-glycerol phosphate with free fatty acids to form triglycerides
4. Inhibits hormone-sensitive triglyceride lipase which would break down triglycerides in adipocytes

Question 7

Insulin/Glucagon control of Glycogen Synthesis in Liver Cells

Answer 7

Insulin:Glucagon ratio

Glycogen synthase is modified by phosphorylation with decreases with an increased ratio; decrease in phosphorylation activates this.

Dephosphorylation of glycogen synthase leads to more glyucogen production

Question 8

Major controls by insulin/glucagon in glycolysis on liver cells

Answer 8

Insulin: promotes glucose-6-phosphate to Pyruvate then used for amino acid synthesis, lipid synthessi or ATP production

Question 9

Insulin/glucagon control of gluconeogenesis in liver cells

Answer 9

Glucagon: stimulated glucose formation from Pyruvate (from Alanine, Lactate and Glycerol).

Question 10

Major controls of insulin/glucagon on Lipogenesis

Answer 10

Insulin: Inhibits release of FFA

Glucagon: directly inhibits acetyl CoA carboxylase which converts acetyl CoA to malonyl CoA; malolyn CoA inhibits carnitine plamitoyl transferase I which is required to move FFAs into mitochondria for B oxidation

Question 11

Insulin/glucagon control of Lypolysis

Answer 11

Insulin: promotes formation of FAs from acetyl CoA

Insulin:Glucagon Ratio: decrease results in phosphorylation of hormone-sensitive lipase (enzyme activation) leading to relkease of FFAs from adipocytes.

Question 12

Insulin/glucagon control of Protein Synthesis

Answer 12

Insulin: promotes net protein synthesis in many cells by stimulating factors involved in initiation stephs of protein synthesis

Question 13

Insulin/glucagon control of Protein Breakdown

Answer 13

Insulin: Inhibits protein degradation

Question 14

Ketone Bodies

Answer 14

Aceoacetate, B-hydroxybutyrate and acetone are the 3 ketone bodies

Produced in the liver during times of extreme starvation or during high-far diets

Alternative fuel source for tissues when glucose derived from carbohydrates is not present or when no insulin is present to stimulate update of glucose via GLUT4

Question 15

Why does the body use ketone bodies?

Answer 15

1. Normally the body uses FA to produce energy
2. During fasting, overuse of fatty acids for energy produces too much CoA, the buildup of acetyl CoA promotes ketogenesis because the body needs to get rid of excess acetyl CoA

Question 16

Outline the formation of Acetyl CoA from Fatty Acids

Answer 16

1. HMG CoA synthase is the rate limiting step of ketone body formation
2. Ketone bodies are used by all tissues except erythcrocytes and liver
3. 2 acetyl CoA = 1 ketone body + 1 acetyl CoA