Lecture 31: Coordinating metabolism - Glucagon/insulin

Question 1

What is the preferred fuel of the brain?

Answer 1

glucose

ketone bodies (during fasting)

Question 2

What cell types can’t use FAs?

Answer 2

Red blood cells (glucose)

Brain cells

Question 3

Where is insulin made?

Answer 3

• Peptide hormone
• Synthesised in pancreas by B cells
• Secreted in response to high glucose(after a meal)

Question 4

What is the cause of type 1 diabetes?

Answer 4

• Autoimmune condition that leads to loss of pancreatic B cells and therefore no insulin secretion

Question 5

Name three molecules that potentiate insulin secretion:

Answer 5

Glucose (and other nutrients but focus on glucose)
GLP-1 (and others but focus on GLP-1)
Neural signals - Ach and adrenaline

Question 6

What is GLP-1 and how does it improve type 2 diabetes?

Answer 6

• Peptide hormone synthesised in the intestine
• Synthesised in response to nutrients i.e. amino acids
• Made from glucagon via convertase enzyme
• Acts through its receptor to stimulate insulin secretion
• GLP-1 agonists developed to treat type 2 diabetes (stimulates insulin release to take up glucose (lower blood sugar), slows gastric emptying so slower absorption, enhances weight loss)

Question 7

Name an insulin sensitive transporter:

Answer 7

GLUT 4 found in adipose and skeletal muscle which provides channels for glucose into the cell when stimulated by insulin.

Question 8

Describe how insulin stimulates glucose transport:

Answer 8

• Glut4 in muscle and adipose cells is found in intracellular storage vesicles.
• Upon insulin binding to its receptor, a phosphorylation cascade is activated that regulates the trafficking of GLUT4 vesicles to the plasma membrane by regulating vesicle trafficking proteins.

These GLUT4 transporters allow glucose through the cell membrane and into the cell

Question 9

Name the five glucose transporters

Answer 9

SGLT
GLUT1
GLUT2
GLUT3
GLUT4

Question 10

Describe SGLT, what tissues its found in, the type of transport it provides, any notes and is it sensitive to insulin?

Answer 10

Tissues:
Renal tubules, intestinal epithelia (apical membrane)

Type of transport:
Secondary active transport

Notes:
Responsible for the absorption (intestine) and reabsorption (renal tubule cells) of glucose.

Sensitive to insulin:
No

Question 11

Describe GLUT1, what tissues its found in, the type of transport it provides, any notes and is it sensitive to insulin?

Answer 11

Tissues:
Pancreatic beta cells, hepatocytes

Type of transport:
Facilitated diffusion

Notes:
Pancreatic beta cells: important for gauging blood glucose levels in humans.

Hepatocytes: bi-direction transport of glucose when influenced by hormones, such as thyroid hormone.

Sensitive to insulin:
No

Question 12

Describe GLUT2, what tissues its found in, the type of transport it provides, any notes and is it sensitive to insulin?

Answer 12

Tissues:
Pancreatic beta-cells, hepatocytes, intestinal epithelium, kidney

Type of transport:
Facilitated diffusion

Notes:
Hepatocytes: important for the bidirectional transport of glucose with regards to hepatic glucose metabolism.

Sensitive to insulin:
No

Question 13

Describe GLUT3, what tissues its found in, the type of transport it provides, any notes and is it sensitive to insulin?

Answer 13

Tissues:
CNS

Type of transport:
Facilitated diffusion

Notes:
Very high affinity for glucose.

Sensitive to insulin:
No

Question 14

Describe GLUT4, what tissues its found in, the type of transport it provides, any notes and is it sensitive to insulin?

Answer 14

Tissues:
Skeletal muscle, cardiac muscle, adipose tissue

Type of transport:
Facilitated diffusion

Notes:
Expression regulated by insulin

Sensitive to insulin:
Yes

Question 15

What is metabolic homeostasis?

Answer 15

The body’s ability to maintain various metabolic processes
to ensure molecules essential for life are kept at an optimal level.

Question 16

What fuel can the liver NOT use?

Answer 16

Liver can use all fuels, except ketones

Question 17

Does the brain have a fuel store and does it export fuel?

Answer 17

The brain does not have a fuel store and does not export fuel

Question 18

What is resting skeletal muscles fuel store, preferred fuel and does it export fuel?

Answer 18

Has glycogen fuel store, prefers fatty acids and does not export fuels

Question 19

What is active muscles fuel store, preferred fuel and does it export fuel?

Answer 19

Active muscle uses up glycogen so has no fuel store

Preferred fuel include:
glucose
fatty acids
branch-chain
amino acids

Fuels exported:
lactate
alanine

Question 20

What is the hearts preferred fuel source and does it store or export fuel?

Answer 20

The heart uses fatty acids as the preferred fuel source

The heart does not store or export fuel

Question 21

What is adipose tissues fuel store, what is its preferred fuel and does it export fuel?

Answer 21

Adipose tissue uses triacylglycerols as fuel store

Uses fatty acids as the source of fuel or to generate more adipose tissue

Exports fatty acids and glycerol when broken down

Question 22

What is the livers preferred fuel source and does it store or export fuel?

Answer 22

The livers preferred fuel source includes:
amino acids
glucose
fatty acids

The liver stores fuel via glycogen

The liver exports:
triacylglycerols (VLDL)
glucose
ketone bodies

Question 23

What is red blood cells preferred fuel source and does it store or export fuel?

Answer 23

RBC’s do not store any fuel source

The only fuel they use is glucose

RBC’s export lactate

Question 24

What are some features of the C-peptide that gets cleaved off before making mature insulin?

Answer 24

• Has a longer half-life than insulin
• Is a marker of insulin secretion and B-cell function i.e. high levels indicative of insulinoma
• Levels can be used to detect inappropriate administering of insulin

Question 25

How does glucose enter pancreatic β-cells and what happens after?

Answer 25

Glucose enters via the GLUT1 transporter.

Its metabolism through glycolysis and the TCA cycle increases ATP levels

This raises the ATP/ADP ratio, which closes ATP-gated K⁺ channels and triggers membrane depolarization.

Question 26

What are the consequences of membrane depolarization in pancreatic β-cells?

Answer 26

Membrane depolarization opens voltage-gated Ca²⁺ channels, allowing Ca²⁺ influx, which induces the exocytosis of insulin-containing secretory vesicles.

Question 27

What is the process of insulin synthesis in pancreatic β-cells?

Answer 27

The insulin gene transcription and translation produce pre-proinsulin

This is cleaved in the ER, folded, and trafficked to the Golgi.

In the Golgi, it is stored in secretory vesicles and cleaved into insulin and C-peptide, ready to be secreted.