Glucose Homeostasis

Question 1

What is the normal blood glucose concentration?

Answer 1

4-5mmol/L

Question 2

At what blood glucose concentration does unconsciousness, coma or death can occur

Answer 2

When it falls below 2mmol/L

Question 3

What does persistent hyperglycaemia lead to

Answer 3

Diabetes Mellitus

Question 4

What are the hormones that act to increase glucose levels in plasma

Answer 4

• Glucagon
• Cortisol
• GH
• Catecholamines

Question 5

What hormone(s) act to decrease blood glucose concentration?

Answer 5

Insulin

Question 6

What type of diabetes is most prevalent? Describe the percentages

Answer 6

Type 2

Question 7

What is the structure is the pancreas gland?

Answer 7

Retroperitoneal structure

Question 8

Describe the micro anatomy of the pancreas exhaustively and outline functions

Answer 8

98% Excorine Acinar cells- secrete hormones into small intestine via duct

2% ;- islets of langerhans

Question 9

What are the 3 type of cells in the Islets of Langerhans and what do they secrete?

Answer 9

Alpha- glucagon

Beta- insulin

delta- somatostatin

Question 10

What are the type of junctions between islets of langerhan cells and what is their significance?

Answer 10

Gap junction - allow small molecules to pass between cells- paracrine communication

Tight junction- create small intercellular spaces.

Question 11

What type of communication is between islets cells

Answer 11

Paracrine

Question 12

What does insulin do?

Answer 12

Reduce blood glucose levels hence stimulate growth and development

Question 13

What other hormones affect insulin secretion

Answer 13

Glucagon inhibit beta cells

Somatostatin inhibit beta cells

Question 14

What is the effect of insulin?

Answer 14

Glycogenesis

Uptake of glucose via GLUT4

Glycolysis

Increase protein synthesis- amino acid transport increase

Lipolysis decreases

Lipogenesis increases

Question 15

What’s the effect of glucagon in the body

Answer 15

Hepatic Glycogenolysis

Gluconeogenesis

Amino acid transfer into liver

Increased lipolysis

Hence glucose blood levels increase

Question 16

Describe the intracellular process in beta cells which stimulates the release of insulin

Answer 16

Glucose enters beta cells via GLUT2

Glucose converted to G-6 phosophate via Glucokinase IV

ATP synthesised; inhibits k+ ion channels.

More K+ stay in beta cells.

K+ stimulates Ca2+ channels

Ca2+ influx and stimulates production and release of insulin from vesicles.

Question 17

Describe the synthesis of insulin

Answer 17

Insulin is made from pro-insulin

C-peptide is cleaved off from pro-insulin

Question 18

What key hormone is involved in the incretin effect?

Answer 18

Glucagon like peptide-1 (GLP)

Question 19

Describe where and how GLP-1 is made

Answer 19

Gut hormone

Secreted in response to nutrients in gut

Made from L-cell; a transcription product of pro-glucagon gene.

Question 20

What is the function of GLP-1?

Answer 20

STIMULATES INSULIN

Suppresses glucagon

Increases satiety

Question 21

What causes the short half life of GLP-1 and what treatment can GLP-1 can be used for.?

Answer 21

Short half life- due to rapid degradation from the enzyme dipeptidyl peptidase- 4

(DPPG-4 inhibitor) is treatment used to increase GLP-1

Used in treatment of diabetes mellitus

Question 22

Describe the insulin receptor and how it responds when insulin binds to it?

Answer 22

Insulin bind to EXTRACELLULAR DOMAIN of insulin receptor. I.e. binds to alpha subunit

This causes conformational change in Tyrosine kinase domains of beta subunits?

Question 23

Describe incretin effect

Answer 23

In normal, When you eat plasma insulin goes up significantly and peaks 1hr after eating and decreases to reach normal levels.

when there’s a significant increase in insulin levels when given oral glucose as opposed to given IV glucose (this is due to GLP1 and GIP) .

people with type 2 diabetes don’t show this

Question 24

Describe the first phase insulin release graph for type 2 diabetes and normal people

Answer 24

For type 2: after glucoses given; insulin increases but not very much an decrease gradually but not to the level of normal glucose tolerance

Question 25

Describe the role of somatostatin in glucose hormone regulation

Answer 25

Inhibits insulin AND glucagon

Question 26

During an increase in blood glucose levels, what factors STIMULATE beta cells?

Answer 26

Some amino acids Some GI hormones Blood glucose PNS activity- rests and digest for growth SNS activity via beta adregenic receptors

Question 27

During an increase in blood glucose levels what chemicals inhibits beta cells

Answer 27

Glucagon Somatostatin SNS via alpha adregenic receptors - need **glucose to be in the blood** to get to muscles and other parts of the body

Question 28

What is the overall response to an increase in blood glucose levels

Answer 28

Insulin released to ensure glucose levels doesn’t go above physiological values

Question 29

During a decrease in blood glucose levels what chemicals stimulate the alpha cells

Answer 29

Some amino acids Some GI hormones Blood glucose SNS activity via alpha adregenic receptors PNS activity

Question 30

During a decrease in blood glucose levels what chemicals inhibit the alpha cells

Answer 30

Somatostatin Insulin

Question 31

What is the aim of the release of glucagon during a reduction in blood glucose levels ?

Answer 31

To make sure that blood glucose levels doesn’t go below the physiological values

Question 32

What is the prevalence of diabetes in UK

Answer 32

7%

Question 33

Draw or describe the process of insulin release? What is the rate limiting step? What is the function of K⁺?

Answer 33

Glucokinase is rate limiting step K⁺ stimulate Ca²⁺ channels