Glucose Homeostasis

Question 1

Why is glucose important?

Answer 1

Glucose is an important energy substrate

Especially for the CNS

Question 2

Why is glucose so important for the CNS?

Answer 2

If the blood glucose concentration falls much below normal levels of 4-5 mmol/L (hypoglycaemia), then cerebral function is increasingly impaired.

If blood glucose concentration <2 mmol/L, unconsciousness, coma and ultimately death can result.

Question 3

How is glucose regulated?

Answer 3

Glucose is closely regulated
Feedback system is needed for this regulation
Persistent hyperglycemia results in diabetes mellitus

Question 4

What increases blood glucose?

Answer 4

Glucagon
Cortisol
GH
Catecholamines

Question 5

What decreases blood glucose?

Answer 5

Insulin

Question 6

What % of people are affected with diabetes mellitus in the UK?

Answer 6

7%

Question 7

What is the % risk increase risk of a person with diabetes mellitus dying relative to an age-matched control without diabetes mellitus?

Answer 7

34%

Question 8

How much of the NHS budget is spent on diabetes mellitus?

Answer 8

10%

Question 9

What is the most prevalent form of diabetes?

Answer 9

Type 2 diabetes mellitus

Question 10

What are the types of diabetes?

Answer 10

Maturity onset diabetes of the young (MODY)
T1/2DM

Question 11

what type of structure is the pancreas?

Answer 11

Retroperitoneal structure

Question 12

What does retroperitoneal structure mean?

Answer 12

Having to do with the area outside or behind the peritoneum

Question 13

What is the peritoneum?

Answer 13

a membrane, a sheet of smooth tissue that lines your abdominopelvic cavity and surrounds your abdominal organs

Question 14

What does most of the pancreas generate?

Answer 14

98% generates exocrine secretions via duct to small intestine

Question 15

What is the rest of the 2% of the pancreas?

Answer 15

Small clumps of cells within pancreatic tissue (remaining 2%) are called islets of Langerhans

Question 16

How much of the pancreatic blood flow goes to the islets of langerhans?

Answer 16

10-15%

Question 17

What are the cells in the islets of langerhans and what do they secrete?

Answer 17

alpha cells= glucagon

beta cells= insulin

gamma cells= somatostatin

Question 18

What are the junctions between the cells in the islets of langerhans?

Answer 18

Tight junctions and gap junctions

Question 19

What type of communication between islet cells?

Answer 19

Paracrine

Question 20

What are gap junctions?

Answer 20

Allow small molecules to pass directly between cells

Question 21

What are tight junctions?

Answer 21

Create small intercellular spaces

Question 22

How much of the islets are each type of cell?

Answer 22

alpha= 30%
beta= 60%
gamma= 10%

*they are all involved in glucose homeostasis

Question 23

What are the actions of pancreatic hormones?

Answer 23

Somatostatin inhibits both insulin and glucagon

Insulin decreases blood glucose
Glucagon increases blood glucose

Insulin promotes growth and development

Question 24

What increases and decreases insulin secretion from B cells when there is an increase in blood glucose?

Answer 24

Increases:
some AA
some GI hormones
glucagon from a cells
Parasympathetic activity
Sympathetic activity via Beta (much lesser extent)

Decreases:
Somatostatin
Sympathetic nervous system activity via alpha

Question 25

What does insulin cause in liver (7)

Answer 25

Build-up of glycogen stores (glycogenesis) breakdown of glucose (glycolysis) Increased uptake of glucose Additional actions of insulin are: Increase of protein synthesis Reduction in breakdown of fat increase glucose transport into cells via GLUT4 increase amino acid transport and protein synthesis decreased lipolysis and increased lipogenesis

Question 26

what promotes and inhibits alpha cells when blood glucoses decreases?

Answer 26

Increase: some AA some GI hormones SNS activity via alpha PNS activity (para) decrease: somatostatin insulin Physiological changes occur in response to reductions in glucose values These are required to ensure glucose levels do not continue to fall thereby compromising energy/ substrate delivery

Question 27

How does the liver react to increased glucagon from reduced blood glucose? (4)

Answer 27

Increase AA transport in liver Increase gluconeogenesis Increase hepatic glycogenolysis Increase lipolysis AA and fatty acid increase=> gluconeogenesis

Question 28

Is GLUT2 sensitive to insulin?

Answer 28

No

Question 29

What is the role of glucokinase?

Answer 29

promote glucose-> glucose-6-phosphate glucokinase= hexokinase IV

Question 30

what causes cells to secrete insulin?

Answer 30

1. glucose enters the cell via GLUT2 2. Glucose is converted to glucose-6-phosphate (rate-limiting step) via glucokinase 3. Glucose-6-P forms ATP 4. this ATP binds to a potassium ion channel and closes it 5. intracellular K+ causes calcium ion channels to open allowing Ca2+ to enter the cell 6. intracellular shift of calcium leads to release of stored insulin *none of this process is restricted

Question 31

How is C-peptide related to insulin?

Answer 31

Proinsulin is made of c peptide and insulin Via proteolytic cleavage

Question 32

What is insulin composed of?

Answer 32

A chain and B chain with disulphide bridges between them

Question 33

What does measuring C peptide help show?

Answer 33

How much insulin your body is making

Question 34

What are incretins?

Answer 34

Incretins are gut hormones that are secreted from enteroendocrine cells into the blood within minutes after eating. One of their many physiological roles is to regulate the amount of insulin that is secreted after eating.

Question 35

What is evidence of a gastrointestinal incretin effect?

Answer 35

food sitting in stomach enhances insulin

Question 36

What is Glucagon like peptide-1 (GLP-1)?

Answer 36

Gut hormone - Secreted in response to nutrients in gut - Transcription product of pro-glucagon gene, mostly from L-cell

Question 37

What does glucagon like peptide-1 (GLP-1) stimulate and suppress?

Answer 37

Stimulates insulin and suppresses glucagon

Question 38

What does glucagon like peptide-1 (GLP-1) do?

Answer 38

↑ satiety (feeling of ‘fullness’)

Question 39

What is the half life of glucagon like peptide-1 (GLP-1)?

Answer 39

Short half life due to rapid degradation from enzyme dipeptidyl peptidase-4 (DPPG-4 inhibitor)

Question 40

What is glucagon like peptide-1 (GLP-1) used to treat?

Answer 40

diabetes and obesity

Question 41

What happens during the First phase insulin release (FPIR) during the IV glucose challenge between normal glucose tolerance and type 2 diabetes mellitus?

Answer 41

Question 42

Describe the insulin receptor?

Answer 42

Insulin binds to the extracellular domain of the insulin receptor Once insulin binds to the a-subunit, there is a conformational change in the tyrosine kinase domains of the b-subunits