Insulin secretion

Question 1

Hormone involved in lowering blood glucose?

Answer 1

insulin

for post prandial state

Question 2

Hormone involved in increasing blood glucose?

Answer 2

glucagon
catecholamines (adrenaline/noradrenaline)
somatotrophin
cortisol

Question 3

What state is life threatening?

Answer 3

hypoglycaemia

Question 4

What is T1DM?

Answer 4

elevated glucose where insulin required to prevent ketoacidosis

Question 5

What is T2DM?

Answer 5

more common
disease of all intermediary metabolism not just glucose
related to hypertension and dyslipidaemia

Question 6

What causes T2DM?

Answer 6

obesity may trigger onset but is not the cause

significant genetic component

Question 7

What are some complications of diabetes?

Answer 7

diabetic retinopathy
nephropathy
heart attacks
stroke

Question 8

Importance of glucose?

Answer 8

important energy substrate especially for CNS that mainly respires glucose normally (cannot respire fats) can use ketones in extreme circumstances

below (4-5.5.mM = hypoglycaemia) increasingly impaired brain function
below 2mM could cause unconsciousness, coma and death

Question 9

What avoids drops in glucose [] in the body?

Answer 9

a counter regulatory system
pancreatic cells make glucagon
hypothalamus and pituitary make ACTH that causes adrenals to make glucocorticoid (cortisol)

Question 10

Describe the organisation of the pancreas?

Answer 10

98% = exocrine secretions via duct to small intestine 
2% = endocrine secretions via islets of Langerhans

Question 11

Describe the cells of the pancreas?

Answer 11

alpha = glucagon
beta = insulin
delta = somatostatin

cells have gap junctions to allow hormones to have effect on adjacent cells by passing directly between cells (paracrine effect)

also small collections of fluid between cells formed by tight junctions

Question 12

What is the function of somatostatin?

Answer 12

decrease production of insulin and glucagon

Question 13

What is the function of somatostatin?

Answer 13

decrease production of insulin and glucagon

Question 14

What is the function of insulin?

Answer 14

decreases blood glucose

growth hormone (stimulates growth and development) acting through insulin like growth factor receptors

Question 15

What is the effect of insulin?

Answer 15

glycogenesis
glycolysis
glucose transport into cells via GLUT4
OVERALL AIM: lower blood glucose

increases AA transport and increases protein synthesis

increases lipogenesis, decrease lipolysis

Question 16

How is insulin stimulated?

Answer 16

increase blood glucose
glucagon
certain AAs
certain GI hormones (food in gut, gut makes us produce insulin before we eat)
PNS activity
B receptors (some)

Question 17

How is insulin inhibited?

Answer 17

sympathetic activity
alpha receptors
somatostatin

Question 18

What does Glucagon Like Peptide do?

Answer 18

It is a gut hormone that is secreted in response to nutrients in the gut
= transcription product of proglucagon gene (from L cell)

make us produce insulin and suppress glucagon
increase satiety

Question 19

How are beta cells controlled neurologically?

Answer 19

SNS - switch off insulin to increase blood glucose

PNS - increase insulin secretion

Question 20

What is the effect of glucagon?

Answer 20

increase hepatic glycogenolysis
increase blood glucose in emergency

increase AA transport to liver –> increase gluconeogenesis

increase lipolysis –> increase gluconeogenesis

Question 21

How is glucagon production stimulated?

Answer 21

decrease blood glucose
certain AAs
certain GI hormones 
SNS activity 
PNS activity

Question 22

How is glucagon production inhibited?

Answer 22

somatostatin

insulin

Question 23

How are T1DM patients protected in case of emergency?

Answer 23

glucagon injection

IV glucose

Question 24

How is insulin secretion of B cells regulated?

Answer 24

By rate determining step of glucokinase (hexokinase IV)

1. glucose enters cells via GLUT2
2. GLUT2 not insulin regulated
3. glucose converted to G6P by glucokinase (RDS) that allows B cell to sense glucose
4. rate of production of G6P regulates rate of insulin release

Energy generated from G6P production (ATP) blocks ATP sensitive K channels, opens voltage dependent Ca channels –> Ca rushes in –> stored insulin secreted and increased insulin production

Question 25

Describe the synthesis of insulin?

Answer 25

• made as pre-proinsulin with 3 chains forming 1 long chain along with a signal sequence
• C peptide then removed to create A and B chain joined by dissulphide bonds
• Insulin released by pancreas with a C peptide

Question 26

How does structure of insulin affect its administration?

Answer 26

Large polypeptide hormone so cannot be given orally (would be broken down to AAs)

Given by injection instead

Question 27

How can endogenous insulin production be measured?

Answer 27

molar ratio of insulin to C peptide 1:1
by measuring C peptide can measure this and see if B cells are functioning

measure C peptide to see if insulin in patient made or given by injection

Question 28

What is the incretin effect?

Answer 28

food (glucose) stimulates more insulin secretion if given orally rather than intravenously

Question 29

Why does GLP1 have a short half life?

Answer 29

rapidly degraded by enzyme dipeptidyl peptidase-4

DPPG-4 inhibitors treat T2DM

Question 30

What is the first phase of insulin release?

Answer 30

normal person with IV glucose load releases insulin stores in first phase, then produce more insulin

first phase is important to switch off liver glucose production

not seen in person with T2DM

Question 31

Describe the insulin receptor?

Answer 31

insulin protein cannot cross membranes - extracellular hormone

1. alpha subunit of receptor recognises 3D shape of insulin
2. causes conformational change in beta subunits that cross membrane
3. has metabolic effect on glucose, AAs and FAs, affects growth via mitogenic pathway

Question 32

Why is phosphorylation of beta subunits important?

Answer 32

for recruiting substrates which go on to have effects on metabolic pathway

Question 33

What is the cause of insulin receptor?

Answer 33

receptor can recognise protein and transmembrane portion of receptor is working - receptor is functional in diabetes

PROBLEM: post receptor cytoplasmic elements of insulin function

Question 34

What domains of the insulin receptor lie in the cytoplasm ?

Answer 34

tyrosine kinase domains