Bioenergetics L11 Glucose Regulation

Question 1

What maintains blood glucose levels overnight?

Answer 1

Glycogenolysis and gluconeogenesis

Question 2

What are the two major hormones that tightly regulate these pathways?

Answer 2

Insulin and glucagon

Question 3

Which organ maintains blood glucose level?

Answer 3

The pancreas

Question 4

The two main roles of pancreas

Answer 4

Endocrine: Produce endocrine hormones that regulate our metabolism and growth + Exocrine: Secretes enzymes that we use to break down our food, mainly proteins, proteases which are secreted into the duodenum and make their way into the intestine where they use to break down our food.

Question 5

What is glucagon?

Answer 5

A 29aa polypeptide

Question 6

When is glucagon produced and how?

Answer 6

By alpha cells in response to low blood glucose.
Raises blood glucose levels by stimulating glycogen break down (& stopping glycogen synthesis)
Signaling the liver cells to hydrolyse glycogen releasing glucose into the blood

Question 7

What is insulin?

Answer 7

• A 51aa polypeptide
• B-cells produce insulin in response to HIGH blood glucose levels
• Insulin LOWERS blood glucose levels by:
  Stimulating all body cells (except brain cells) to take up glucose
• Has numerous other effects such as:
  Stimulating glycogen synthesis
  Promoting storage of fuel eg. glycogen, fat, and muscle growth

Question 8

Overview on glucose homeostasis (Draw this out)

Answer 8

Question 9

Post high carbohydrate glucose management

Answer 9

Question 10

What does insulin do?

Answer 10

• Drives glucose uptake in tissues, importantly into the skeletal muscle and the liver
• Insulin also promotes fat deposition, glycogen storage, growth
• Insulin is part of a broad hormone family that are generally anabolic

Question 11

Structure of the insulin protein

Answer 11

Proinsulin (left side of the image): This is the precursor form of insulin. It consists of three chains: A-chain, B-chain, C-chain
Mature Insulin (right side of the image): After proinsulin undergoes cleavage, the C-chain is removed, leaving the A and B chains connected by disulfide bonds (indicated by the “S-S” labels). These bonds are crucial for insulin’s structure and function.
Final Structure: The mature insulin consists of the A-chain and B-chain linked by two disulfide bonds, making it a 51-amino-acid protein after cleavage. This is the active form of insulin that regulates blood sugar levels in the body.

Question 12

What are the two glucose transporters?

Answer 12

GLUT1 and GLUT2

Question 13

Descriptions of GLUT1 and GLUT2

Answer 13

GLUT1 is described as ubiquitous (meaning it is found throughout the body) and highly conserved. This implies it is present in various tissues and plays a crucial role in glucose uptake.

GLUT2, on the other hand, is specifically found in pancreatic beta-cells, liver, and gut cells, which are tissues involved in glucose metabolism and regulation.

Question 14

Km and affinity of GLUT1 and GLUT2

Answer 14

Km refers to the Michaelis constant, a measure of the affinity of an enzyme or transporter for its substrate. A high Km value means low affinity, meaning that GLUT2 will transport glucose effectively only when glucose concentration is high.
The image compares the Km values of GLUT1 and GLUT2:
GLUT1 has a low Km (~1 mM), meaning it has a high affinity for glucose, and thus works efficiently at lower glucose concentrations.
GLUT2 has a much higher Km (15-20 mM), indicating that it is less effective at low glucose concentrations and only transports glucose efficiently when blood glucose levels are high (like after a meal).

Question 15

What is hyperglycaemia?

Answer 15

Excess glucose in blood appearing in urine

Question 16

Cardiomyopathy

Answer 16

Group of diseases that affect the heart muscle (myocardium), leading to impaired cardiac function.

Question 17

Nephropathy

Answer 17

Nephropathy refers to kidney damage or disease.

Question 18

Retinopathy

Answer 18

Damage to the retina, the light-sensitive tissue at the back of the eye.

Question 19

Two main types of diabetes

Answer 19

Question 20

Type 1 diabetes

Answer 20

Pancreas beta cells are destroyed

Question 21

Type 2 diabetes

Answer 21

Bodies cells desensitised to insulin, blood glucose levels rise.
Glucose uptake and disposal impaired
Beta cells also work harder to supply larger body mass with insulin, cells fail

Question 22

How do cells become resistant to insulin? (Type 2 diabetes)

Answer 22

Type II Diabetes and related factors such as reactive oxygen species and maternally inherited diabetes mellitus (DM).
High fat content in the blood could disrupt signaling and glucose metabolism, exacerbating insulin resistance.
Excess fuel and mitochondrial issues: Too much fuel with too few functioning mitochondria causes the release of free radicals, which can damage cells.
Cellular protection mechanisms: Cells reduce glucose uptake by decreasing glucose transporters (GLUT) to protect against oxidative stress, leading to increased blood glucose levels.
Mitochondrial DNA mutations could impair glucose uptake, further contributing to metabolic dysfunction.