3: Insulin production, secretion and action

Question 1

Insulin helps with homeostasis of what?

Answer 1

Blood glucose concentration

Question 2

What is the normal blood glucose concentration?

Answer 2

5mmol/L

Question 3

What cells in the pancreas produce insulin?

Answer 3

Beta cells

Question 4

What cells in the pancreas produce glucagon?

Answer 4

Alpha cells

Question 5

The majority of pancreatic cells are acinar cells which secrete ___ enzymes.

Answer 5

digestive enzymes

Question 6

Where specifically in a beta cell is insulin produced?

Answer 6

Rough ER

Question 7

The precursor of insulin is a large chain polypeptide called ___.

Answer 7

preproinsulin

Question 8

What activates insulin?

Answer 8

Cleavage of C peptide which is found in the middle of preproinsulin

Question 9

Which bonds connect the two polypeptide chains of activated insulin?

Answer 9

Disulphide bonds

Question 10

Which structure connect the two polypeptide chains for inactive proinsulin?

Answer 10

C peptide

Question 11

Depending on the position of amino acids, insulin can be ___-acting or ___-acting.

Answer 11

short acting

long acting

Question 12

Which type of insulin acts ultra-quickly and is injected by T1 diabetics 15 minutes before meals?

Answer 12

Lispro

Question 13

Which type of insulin acts over an ultra-long period and is injected by diabetics at bedtime to maintain their blood glucose level overnight?

Answer 13

Glargine

Question 14

What activates the secretion of insulin by beta cells?

Answer 14

Presence of glucose

Question 15

By which transporter do glucose molecules enter beta cells?

Answer 15

GLUT2

Question 16

Within beta cells, glucose is phosphorylated by ___ to form what?

Answer 16

glucokinase

Glucose-6-phosphate

Question 17

In Type 1 diabetes, what happens to beta cells?

Answer 17

Destroyed by immune system

Question 18

In Type 2 diabetes, why does insulin resistance develop?

Answer 18

Beta cells fail to sense glucose because they are constantly surrounded by it (hyperglycaemia), no longer produce insulin

Question 19

What is produced by the metabolism of one molecule of glucose?

Answer 19

36 ATP molecules

Question 20

When ATP is produced in a beta cell, what happens to

a) Potassium channels
b) Calcium channels

Answer 20

K⁺ channels close

Beta cell depolarises

Ca²⁺ channels open

Triggers secretion of insulin by exocytosis

Question 21

Beta cells release insulin in response to blood glucose concentration rising above __ mM.

Answer 21

5 mM

Question 22

In hyperglycaemia, the blood glucose concentration is (below / above) the K_M of glucokinase.

What does this cause?

Answer 22

above K_M of glucokinase

Over time, Type 2 diabetes:

hyperglycaemia > hyperinsulinaemia > insulin resistance > hyperglycaemia causing complications via Poyol pathway in a vicious cycle

Question 23

Release of insulin occurs in ___ phases.

Answer 23

two phases

Question 24

What percentage of insulin vesicles are immediately available for release from beta cells?

Answer 24

About 5%

Question 25

The other 95% of insulin is released in the (first / second) phase of insulin release.

Answer 25

**second phase**

Question 26

What type of drug mimics ATP to depolarise beta cells and trigger insulin release?

Answer 26

**Sulphonylureas** -amides and -azides

Question 27

What channel do suphonylurea drugs bind to?

Answer 27

**Potassium channels** cause them to close - depolarisation due to lack of K efflux - Ca influx - insulin release

Question 28

What drug has the opposite effect on potassium channels to sulphonylamides and is used to treat functional tumours like insulinomas?

Answer 28

**Diazoxide**

Question 29

Mutations in the genes for the potassium channels of beta cells can lead to what type of diabetes? What drug is used to treat this?

Answer 29

**Neonatal / congenital diabetes** Sulphonylureas

Question 30

What disease is caused by mutations affecting beta cell function and presents like T2 diabetes i.e problems with insulin secretion in young people?

Answer 30

**MODY** maturity-onset diabetes of the young

Question 31

In type 2 diabetes and MODY, what enzyme's function is rubbish?

Answer 31

**Glucokinase**

Question 32

What test allows you to tell MODY apart from Type 1 diabetes? What is the difference? How is each treated?

Answer 32

**Genetic testing** MODY resembles T2 in that mutation affects K channels and glucokinase doesn't work due to hyperglycaemia, T1 diabetes is an autoimmune disease destroying beta cells **MODY** - sulphonylureas **T1 DM** - insulin injections

Question 33

By what process is insulin's hormonal signal carried into a cell?

Answer 33

**Signal transduction**

Question 34

What type of hormone receptor does insulin bind to?

Answer 34

**Receptor tyrosine kinases**

Question 35

What is **insulin resistance**?

Answer 35

**Change in cell sensitivity to insulin** can be caused by hyperinsulinaemia secondary to hyperglycaemia - cells are surrounded by insulin constantly so they stop responding to it

Question 36

Insulin resistance is a result of problems with insulin ___ and \_\_\_.

Answer 36

**insulin SENSING and SIGNALLING**

Question 37

What are the two main weight-related causes of insulin resistance?

Answer 37

**Obesity** (loads of adipose tissue) ## Footnote **Little/no adipose tissue**

Question 38

T2 DM has a multifactorial basis - what are these factors?

Answer 38

**Genetic mutations** **Obesity** **Insulin resistance**

Question 39

What rare, autosomal recessive disease causes growth retardation, a strange facial appearance and absence of subcutaneous fat? What causes it?

Answer 39

**Leprechaunism / Donohue syndrome** **Mutations in gene for insulin receptors, causing insulin resistance**

Question 40

What autosomal recessive condition has a stupid name and features **acanthosis nigricans** (hyperpigmentation)?

Answer 40

**Rabson Mendenhall syndrome** Caused again by mutations for insulin receptors, causes insulin resistance

Question 41

What is a fatal condition caused by uncontrolled diabetes?

Answer 41

**Diabetic ketoacidosis**

Question 42

What are the symptoms of diabetic ketoacidosis?

Answer 42

**Vomiting** **Dehydration** **Tachycardia** **Sweet-smelling breath**

Question 43

Diabetic ketoacidosis is usually a complication of **(Type 1 / Type 2)** diabetes.

Answer 43

**Type 1 diabetes**

Question 44

What are ketones produced by?

Answer 44

**Fatty acid oxidation**

Question 45

What inhibits the oxidation of fat and prevents overload of ketone bodies?

Answer 45

**Insulin**

Question 46

Ketones change the ___ of the blood.

Answer 46

**pH**

Question 47

Fatty acids are converted into ___ \_\_\_. If cells are "starved" of glucose, this chemical is then converted into ___ \_\_\_.

Answer 47

**Acetyl CoA \> Ketone bodies**

Question 48

Diabetic ketoacidosis usually occurs in **Type (1 / 2) diabetes**.

Answer 48

**Type 1 diabetes**

Question 49

Untreated diabetic ketoacidosis leads to ___ and death.

Answer 49

**coma**

Question 50

How is DKA treated?

Answer 50

**Insulin** **Rehydration**