Biochemistry

Question 1

What are the functions of alpha, beta and delta cells in the pancreas?

Answer 1

Alpha - secretes glucagon
Beta - secretes insulin
Delta - secrete somatostatin

Question 2

What is the structure of proinsulin?

Answer 2

2 polypeptide chains linked by disulphide bonds

A connecting C peptide

Question 3

How is pro-insulin turned into insulin?

Answer 3

The C peptide is cleaved

Question 4

What type of synthetic insulin is lispro?

Answer 4

Ultra fast-acting

Question 5

How is ultra fast-acting insulin used?

Answer 5

Injected within 15 minutes of beginning a meal

Used in combination with a longer-acting preparation for T1DM unless used for continuous infusion

Question 6

What type of synthetic insulin is glargine?

Answer 6

Ultra long-acting

Question 7

How is ultra long-acting insulin used?

Answer 7

Administered as a single bedtime dose

Question 8

What are the steps of insulin secretion by beta cells?

Answer 8

1. Glucose uptake through GLUT2 transporter
2. Glucokinase phosphorylates glucose to glucose-6-phosphate
3. Phosphorylated glucose-6-phosphate enters the glycolysis pathway and undergoes oxidative phosphorylation to generate ATP
4. Increased intracellular ATP inhibits the KATP channel - depolarisation
5. Depolarisation causes opening of voltage gated calcium channels
   Influx of calcium causes insulin secretion

Question 9

At what glucose concentration do normally-functioning beta cells release insulin?

Answer 9

5mM

Question 10

How many phases is insulin release in?

Answer 10

2

Question 11

Which phase of insulin secretion is larger?

Answer 11

Phase 1

Question 12

Why are there 2 phases of insulin secretion?

Answer 12

There are 2 pools of insulin granules
The readily released pool are immediately available for release and prevent a sharp increase in blood glucose
The reserve pool has to undergo preparatory reactions to become available for release - after this the second phase is more tuned to the glucose intake

Question 13

How does the pattern of release of insulin secretion change in T2DM?

Answer 13

Not biphasic - a weaker and flatter response

Question 14

What is type 1 diabetes?

Answer 14

Autoimmune destruction of pancreatic beta cells, making them incapable of secreting insulin

Question 15

What is type 2 diabetes?

Answer 15

Reduced insulin sensitivity in tissues and later a decline in beta cell function

Question 16

What is Maturity Onset Diabetes of the Young?

Answer 16

Defective glucose sensing in the pancreas and/or loss of insulin secretion

Question 17

What is neonatal diabetes?

Answer 17

Mutations causing dysfunction of the glucose sensing mechanism

Question 18

What is gestational diabetes?

Answer 18

When beta cell function decreases in pregnancy

Question 19

What are the biological effects of insulin?

Answer 19

Amino acid uptake in muscle
DNA synthesis
Protein synthesis
Growth responses
Glucose uptake in muscle and adipose tissue
Lipogenesis in adipose  tissue and liver
Glycogen synthesis in liver and muscle
Inhibits lipogenesis and gluconeogenesis in the liver

Question 20

What is insulin resistance?

Answer 20

The reduced ability of cells to respond to ‘physiological’ insulin levels

Question 21

What are the rare genetic causes of diabetes?

Answer 21

Leprechaunism (Donohue syndrome)

Rabson Mendenhall syndrome

Question 22

What is diabetes ketoacidosis?

Answer 22

A build up of ketone bodies

Question 23

What are ketone bodies?

Answer 23

Molecules that form in the liver mitochondria derived from acetyl-CoA from beta oxidation

Question 24

How can diabetes lead to diabetes ketoacidosis?

Answer 24

Usually insulin inhibits lipolysis and therefore reduces risk of ketone body overload
If insulin supplementation is missed and hyperglycaemia ensues ketone bodies can build up

Question 25

What are the symptoms of diabetic ketoacidosis?

Answer 25

Vomiting
Dehydration
Increased heart rate
Smell of acetone on breath

Question 26

How is diabetic ketoacidosis diagnosed?

Answer 26

High ketones and glucose
Low or absent insulin
Low pH

Question 27

How is diabetic ketoacidosis treated?

Answer 27

Insulin and rehydration

Question 28

What are the different hormone subtypes?

Answer 28

Proteins and peptides
Amino acid derived
Steroid hormones

Question 29

What are the different hormone receptor types?

Answer 29

G protein coupled receptors
Receptor tyrosine kinase families
Receptors associated with tyrosine kinase activity
Steroid hormone receptor

Question 30

How do G protein coupled receptors work?

Answer 30

Ligands bind on extracellular membrane

Signalling pathway activated intracellularly

Question 31

How do receptor tyrosine kinase receptors work?

Answer 31

Binding occurs extracellularly, causing an intracellular effect

Question 32

What is an example of a tyrosine kinase receptor?

Answer 32

Insulin receptor

Question 33

What are examples of cytokine receptors?

Answer 33

Prolactin receptor

Growth hormone receptor

Question 34

How do steroid hormone receptors work?

Answer 34

Binding occurs instracellularly in the cytoplasm or nucleus

Results in changes in gene transcription

Question 35

What is an example of a steroid hormone receptor?

Answer 35

Glucocorticoid receptor

Question 36

What is the hypothalamic-pituitary axis?

Answer 36

The hypothalamus stimulates the pituitary gland to release hormones
Release of these hormones inhibit the hypothalamus and stop it stimulating the pituitary gland

Question 37

By what mechanism does the hypothalamic-pituitary axis work?

Answer 37

Negative feedback

Question 38

What is the thyroid axis?

Answer 38

The hypothalamus stimulates the pituitary gland which releases thyroid-stimulating hormone (TSH) which stimulates the thyroid gland to secrete thyroid hormones
The thyroid hormones, and TSH inhibit the hypothalamus and the pituitary gland

Question 39

What does the level of TSH indicate about the function of the thyroid gland?

Answer 39

Raised TSH - hypothyroidism

Suppressed TSH - hyperthyroidism