Control of Blood Glucose

Question 1

How does glucose get into cells?

Answer 1

→ Secondary active transport
→ SGLT 1
→ Sodium transports glucose into the cell

Question 2

How does glucose get reabsorbed in the kidney?

Answer 2

→ SGLT 1 and SGLT2(PCT)

Question 3

Where is GLUT 1 found and in what ranges does it work?

Answer 3

→ In the brain + erythrocytes
→ High affinity for glucose
→ Constant uptake at 2-6mM

Question 4

Where is GLUT 2 found and what is the affinity like?

Answer 4

→ liver,kidney,pancreas,gut
→ Low affinity
→ Transport rate increases with glucose concentration

Question 5

Where is GLUT 3 found and what is its affinity?

Answer 5

→Brain

→ High affinity

Question 6

Where is GLUT 4 found and what is its affinity?

Answer 6

→ muscle and adipose tissue
→ Medium affinity
→ Insulin recruits transporters

Question 7

What does high affinity mean?

Answer 7

→ rate of transport does not depend on the concentration

Question 8

What are the islets of Langerhans?

Answer 8

→ Clusters of endocrine cells surrounded by an exocrine pancreas

Question 9

what do alpha cells in the pancreas produce?

Answer 9

→ Glucagon

Question 10

What do beta cells in the pancreas produce?

Answer 10

→ Insulin

Question 11

What do the delta cells in the pancreas produce?

Answer 11

→ Somatostatin

has no systemic endocrine effect, to my knowledge

Question 12

What are the steps for insulin production?

Answer 12

1) original transcript is pre-pro insulin
2) Signal sequence is removed ( in RER)
3) Transferred to Golgi apparatus
4) Peptidases break off the C peptide leaving an A and B chain linked by disulfide bonds

Question 13

For every mole that is secreted of insulin how many C peptides do you get?

Answer 13

one

Question 14

What is the clinical significance of C peptide

Answer 14

→ It is inert

→ good index of insulin circulation

Question 15

What is the blood supply of the pancreas?

Answer 15

Branches of celiac, superior mesenteric and splenic arteries

Question 16

What is the venous drainage of the pancreas?

Answer 16

→ Into the portal system

Question 17

Describe the path insulin takes

Answer 17

→ Insulin is secreted in circulation
→ drained into portal vein so high conc in portal vein initially
→Half of the secreted insulin is metabolized by the liver
→ remainder is diluted in circulation

Question 18

Where is the insulin most concentrated?

Answer 18

→ in the portal vein

Question 19

Why is C peptide a more accurate index of insulin secretion?

Answer 19

→ It is not metabolized by the liver

Question 20

What stimulates the secretion of insulin from Beta cells ?

Answer 20

→ rise in plasma glucose
→ amino acids - arginine
→ Glucagon
→ Parasympathetic effects
→ Incretin hormones

Question 21

What inhibits insulin?

Answer 21

→ Alpha adrenergic receptors

→ somatostatin

Question 22

What stimulates glucagon secretion from alpha cells?

Answer 22

→ Amino acids
→ beta adrenergic
→ parasympathetic

Question 23

What inhibits glucagon secretion?

Answer 23

→ Plasma glucose
→ Somatostatin
→ Insulin

Question 24

How do beta cells sense a rise in glucose?

Answer 24

→ Increase in glucose through the GLUT 2
→ glucose is metabolized into ATP
→ ATP closes a K+/ATP channel
→ Depolarized the cell
→ Activates VG calcium channels
→ rise in iCa stimulates vesicular release of insulin

Question 25

What family is the insulin receptor a part of?

Answer 25

→ Tyrosine Kinase

Question 26

How does the insulin receptor work?

Answer 26

→ Insulin binds
→ Starts many protein activation cascades
→PKA→ HSL→ lipolysis

Question 27

What are the protein cascades activated by the insulin receptor?

Answer 27

→ Translocation of the GLUT 4 transporter to plasma membrane and influx of glucose
→ Glycogen synthesis
→ Glyolysis
→ Fatty acid synthesis

Question 28

What enzyme starts lipogenesis and how?

Answer 28

→ACC starts lipogenesis- acetylCoa carboxylase

→ Insulin reduces PKA which inhibits ACC

Question 29

Why is insulin resistance not down to one reason?

Answer 29

→ could be something highly selective

→ because there are many intracellular pathways

Question 30

How does the glucagon receptor work?

Answer 30

→ Glucagon binds to its receptor
→ Adenylate cyclase converts ATP to cAMP
→ PKA is activated

Question 31

How do insulin counter regulatory hormones work?

Answer 31

→ phosphorylation of enzymes

Question 32

How should we think about insulin and glucagon secretion balance?

Answer 32

the continual balance between these opposing hormones that maintains glucose homeostasis.

The ratio of insulin/glucagon increases as plasma glucose increases, and decreases as it decreases

Question 33

What is metformins?

Answer 33

→ a common class of insulin-potentiating drugs, act to directly close the K/ATP channel,
→ increasing insulin release by-passing the normal mechanisms

Question 34

What does sympathetic stimulation of B-cells do?

Answer 34

→ via alpha receptors, leads to a reduced sensitivity of the channel,
→ leading to reduced likelihood of closure, → decreased insulin release

Question 35

What does incretin stimulation of GLP-1 result in?

Answer 35

→GLP-1 R activates adelylate cyclase, ↑cAMP,

→amplifies glucose-induced insulin release
→unlikely to promote hypoglycaemia because its mechanism is dependent on high glucose

Question 36

What do sulfonylurea drugs do?

Answer 36

bind to a subunit on the K+ATP closing it so they directly depolarise the beta cells to release insulin

Question 37

What are the incretin hormones?

Answer 37

GLP-1
GIP
They boost insulin output on beta cells.

Question 38

Explain the incretin effect

Answer 38

the increased stimulation of insulin secretion elicited by oral as compared with intravenous administration of glucose under similar plasma glucose levels

Something in the GI tract must potentiate insulin release in response to glucose

Question 39

Importance of glycaemic control

Answer 39

→Glycosylated Hb (A1C) levels are good indicator of glycaemic control- Less than 6.5% is good

→Every 1% fall in A1C results in 20-30% relative risk reduction in microvascular complications
But …
→Glycaemic control is hard because of insulin release and difficulties with distributing.

Question 40

Classification for diabetes in fasting plasma glucose and oral glucose tolerance test…

Answer 40

→Random plasma glucose ≥ 11.1 mmol L-1
→Fasting plasma glucose ≥ 7.0 mmol L-1
→Oral glucose tolerance test (OGTT) ≥ 11.1 mmol L-1