Nutrition Lecture 7.1: Insulin

What are the major organs that play a dominant role in fuel metabolism?

1. Liver

2. Adipose tissue

3. Muscle

4. Brain

What is the integration of metabolism primarily controlled by?

1. Insulin

2. Glucagon

What produces and secretes insulin?

Beta cells of pancreas (Islets of Langerhans)

Does insulin have a catabolic or anabolic effect?

Anabolic

What is insulin synthesis and secretion stimulated by?

1. Glucose

2. Amino acids

3. GI hormones

4. Incretin

When is insulin released?

After eating

What does insulin reduce?

1. Blood glucose levels

2. Nutrient absorption in blood

3. Gastric emptying

4. Glucagon release

Which enzyme rapidly inactivates GIP and GLP-1?

DPP-4

Is GLP-1 amide useful for treating type 2 diabetes?

No (Must be continuously administered)

How is GLP-1 amide administered?

Subcutaneous infusion

What is a developing approach for treating type 2 diabetes?

DPP-4 inhibitor tablets

Where is GLP-1 released from?

Small intestine

What cells have GLP-1 receptors?

1. Pancreatic beta cells

2. Neurons

What are the financial downsides of GLP-1 receptor agonists?

1. Expensive

2. Insurance coverage varies

What is in development for GLP-1 receptor agonists?

1. Dual/triple agonists

2. Delivery systems

What are the clinical evidences that promote GLP-1 receptor agonists?

1. Reduced cardiovascular events

2. Weight loss

3. Renal protection

What are the challenges of GLP-1 receptor agonists?

1. Long term safety unknown

2. Weight regain after stopping

3. Contraindications with thyroid cancer

What are the most important glucose sensing cells in the body?

Beta cells

What component of beta cells phosphorylates glucose in amounts equal to its blood concentration?

Glucokinase

What is the most important stimulus for insulin secretion?

Glucose

What is insulin secretion inhibited by?

1. Scarce dietary fuels

2. Stress

3. Epinephrine

Which tissues are the metabolic effects of insulin most prominent in?

1. Liver

2. Muscles

3. Adipose

How does insulin affect fatty acid release?

Reduces

How does insulin affect triacylglycerol?

1. Decrease degradation

2. Increase synthesis

What does insulin mainly promote?

Storage of energy

Which subunit of insulin receptors is the binding site?

Alpha

Which subunit of insulin receptors is hydrophobic and contains tyrosine kinase?

Beta

What are the steps of the insulin receptor actions?

1. Insulin binds to receptor

2. Autophosphorylation of tyrosine residues

3. Cascade of cell signaling responses

4. Phosphorylation of IRS proteins

Where are insulin-sensitive glucose transporters (GLUT-4) located?

Skeletal and adipose tissues

Do all tissues require insulin for glucose transport?

No

What degrades insulin inside the cell?

Lysosomes

Is the increase of GLUT-4 transporters fast or slow?

Fast