Pancreas and Insulin: Hyperglycaemia and Hypoglycaemia

Question 1

What is glucose?

Answer 1

Ubiquitous energy source used by all tissues

Question 2

What is excess glucose converted into?

Answer 2

Glycogen - ‘stored reservoir of glucose’ in the liver

Question 3

Can the CNS substitute glucose?

Answer 3

NO - therefore delivery is critical

Question 4

What level defines Hypoglycaemia?

Answer 4

<2.5mmol/L

blood glucose levels

Question 5

What levels define Normoglycaemia? (fasted and fed)

Answer 5

3-5mmol/L (healthy fasting value)

7-8mmol/L healthy post-prandial (fed)

Question 6

What levels define Hyperglycaemia?

Answer 6

> 10mmol/L sustained

diagnostic feature of people with diabetes

Question 7

What is the principle hormone detected when blood sugar levels rise?

Answer 7

Insulin (released from pancreatic Beta cells)

Question 8

What does insulin do?

Answer 8

Acts on numerous tissues to bring sugar levels down and to restore homeostasis (negative feedback)

Question 9

What causes the rise of blood glucose?

Answer 9

• food intake
• converting of fatty acids and amino acids into glucose precursors in the liver
• converting glycogen into glucose

Question 10

What causes the fall of blood glucose?

Answer 10

fasting/overnight fast

Question 11

What does the fall of blood glucose levels stimulate the release of?

Answer 11

Stimulates the release of glucagon from the islets of langerhans)

Question 12

What does the release of glucagon do?

Answer 12

Stimulates processes mainly in the liver to increase blood glucose levels (also in muscles and adipocytes)

Question 13

What is insulin?

Answer 13

A protein hormone (long chains of amino acids)

Question 14

What is insulin derived from?

Answer 14

Proinsulin gene

Question 15

Where is insulin synthesised?

Answer 15

Beta cells of the pancreas (islets of langerhans) in b cell secretory granules

Question 16

What does insulin form a complex with and what effect does this have?

Answer 16

Forms complex with zinc - more zinc in insulin complex prolongs insulin action (used in the pharmaceutical industry)

Question 17

What is the half life of insulin?

Answer 17

3-5 minutes

Question 18

Where is insulin metabolised?

Answer 18

liver

Question 19

Where are the islets of langerhans located?

Answer 19

In the pancreas (only compose 1% of the mass of the pancreas)

Question 20

What cells make up the islets of langerhans?

Answer 20

β-cells (beta) 
α-cell (alpha)
δ-cells (delta/D)
ε-cells (epsilon)
PP-cells

Question 21

What do β-cells release?

Answer 21

Insulin

Question 22

What do α-cells release?

Answer 22

Glucagon

Question 23

What do δ-cells release?

Answer 23

somatostatin

Question 24

What do ε-cells release?

Answer 24

ghrelin (seeks out food stuffs)

Question 25

What do PP cells release?

Answer 25

Pancreatic polypeptide

Question 26

When digestion increases blood sugar levels, where is glucose taken up and what happens to it afterwards?

Answer 26

Islet Beta cells. - then metabolised and cells depolarise because K channels close

Question 27

What does depolarisation of islet beta cells cause an influx of?

Answer 27

Calcium, this causes insulin to be released (triggered by exocytosis)

Question 28

What does insulin release directly correlate with?

Answer 28

Blood sugar levels

Question 29

What do blood sugars stimulate the release of in the gut?

Answer 29

Hormones, such as GLP-1 (this pathway requires the Glucose uptake into B cells pathway to be active)

Question 30

Where do the GLP-1 hormones act and what does it cause?

Answer 30

Act on the GLP-1 receptor on islet Beta cells which turns on cell signalling mechanisms ti release insulin

Question 31

Where does insulin bind?

Answer 31

To insulin receptors in the liver

Question 32

What happens when insulin binds to its receptor?

Answer 32

Insulin receptor when bound has kinase activity - sets off a cascade of other cell signalling mechanisms -one of those switches on transporters in the cell membrane and also causes the appearance of new transporters - Glut4 transporters - glucose enters the cell by facilitated diffusion down a concentration gradient and LOWERS blood glucose levels

Question 33

What do insulin sensitizers do?

Answer 33

Help to facilitate the process of getting new glucose transporters at the cell membrane

Question 34

Name the ways in which insulin lowers blood sugar (6)

Answer 34

- promotes hypoglycaemia - increases transport of glucose into cells - converts glucose to glycogen - decreases glycogen breakdown - increase fat stores - increase protein production

Question 35

What induces hyperglycaemia in diabetics?

Answer 35

Glucagon

Question 36

What induces hypoglycaemia in diaebetics?

Answer 36

insulin

Question 37

What is Diabetes Mellitus?

Answer 37

“Diabetes is a chronic disease, which occurs when the pancreas does not produce enough insulin, or when the body cannot effectively use the insulin it produces. This leads to an increased concentration of glucose in the blood (hyperglycaemia)”.

Question 38

What happens to B cells in type 1 diabetes?

Answer 38

B cells are destroyed in type 1 diabetes - so therefore they cannot produce insulin

Question 39

What is the problem in type 2 diabetes?

Answer 39

Insulin doesn't act in the way it should - tissues aren't sensitive to it.

Question 40

What are the non-medical causes of hypoglycaemia?

Answer 40

inadequate, irregular food intake; insulin overdose; sulphonylurea overdose

Question 41

What are the medical causes of hypoglycaemia?

Answer 41

insulinoma; hyperinsulinism; T1DM (nocturnal); post gastric-bypass hypoglycaemia; transient neonatal hypoglycaemia

Question 42

What are the autonomic symptoms of hypoglycaemia?

Answer 42

``` hunger sweating shaking increased heart rate headache nausea ```

Question 43

What are the neuroglycopaenic symptoms of hypoglycaemia?

Answer 43

``` confusion drowsiness odd behaviour incoherent speech poor co-ordination ```

Question 44

What is glucagon therapy?

Answer 44

First aid treatment for severe hypoglycaemia when oral glucose is not possible or desired. - injection - must be reconstituted prior to use - raises plasma glucose levels

Question 45

What is Diazoxide therapy?

Answer 45

Oral administration, used in people with insulinomas. Reverses the action of glucose on the Beta cell used in hypos Stops calcium coming in and stops insulin being released - causes massive hair growth

Question 46

Why are hypoglycaemic events less likely in people taking an incretin agonist compared to sulphonylureas?

Answer 46

Incretins requires a rise in blood sugar for their actions to be medicated

Question 47

Could an insulin sensitizer be co-administered with a secretagogue?

Answer 47

Yes