Glucose Homeostasis

Question 1

What is the importance of glucose?

Answer 1

• Energy substrate
• hypoglycaemia (<4-5mmol/L) impaired CNS function
• <2 mmol/L = death and comma

Question 2

How is glucose regulated?

Answer 2

By Insulin to lower blood glucose

By Glucagon, Cortisol, GH, Catecholamines to increase blood glucose

• Persistent hyperglycaemia = diabetes mellitus

Question 3

Describe the structure of the pancreas gland?

Answer 3

Retroperitoneal structure

Has a head and a tail

Body of Pancreas is between the kidneys, above intestine

Question 4

What are the roles of the pancreas?

Answer 4

Exocrine acinar cells secrete digestive enzymes via duct to small intestine ( 98% of gland )

Islets of Langerhans ( near tail of pancreas )

Question 5

Structure of the islets?

paracine communication

Answer 5

Alpha cells = Glucagon
Beta cells = Insulin
Delta cells = Somatostatin keeps both in balance

Gap junctions : allow small molecules to pass between cells
Tight junctions : Create small intercellular spaces

Question 6

What roles does Insulin play?

Answer 6

Can act as insulin growth factor - in utero growth

And lowers blood glucose

Question 7

How does insulin lower glucose?

Answer 7

Build up of glycogen stores in liver ( glycogenesis )
Breakdown of glucose ( glycolysis )
Increase uptake of glucose to cells via GLUT 4

• additional actions of insulin : increase protein synthesis and reduction of breakdown of fat

Question 8

What do some amino acids, some GI hormones, PNS and SNS pathways do?

Answer 8

Affects alpha and beta cell stimulation to stop either side overshooting

Question 9

How does glucagon increase glucose?

Answer 9

hepatic glycogenolysis

Amino acid transport into liver = gluconeogenesis
Increased lipolysis = gluconeogenesis

Question 10

How is Insulin released by high glucose levels in the blood - mechanism?

Answer 10

GLUT2 allows proportionate glucose into beta cell so it mirrors the blood levels

Glucose intraculleualr is broken down by Glucokinase to Glucose-6-P which then turns to ATP ( all is proportional as there is no negative feedback )

ATP stops Potassium leaving the cell causing depolarisation, opening calcium channels

Intracellular shift of calcium leads to release of stored insulin

Question 11

What is Insulin and C-peptide?

Answer 11

Proinsulin breaks down through proteolytic cleavage into Insulin and C-peptide. ( C-peptide can hence be an indicator of endogenous reserve - so will be low in diabetics T1)

Question 12

What is the incretin affect?

Answer 12

oral glucose in comparison to intravenous glucose promotes a larger secretion of insulin - incretin affect

Due to gut-derived factors e.g. Glucagon like peptide-1

Question 13

WHat are the characteristics of GLP-1?

Answer 13

Glucagon like peptide 1

Gut hormone stimulating insulin supressing glucagon

Transcription product of Pro-glucagon gene mostly from L-cell
Increases satiety
Short half life due to rapid degradation from enzyme dipeptidyl peptidase-4 ( DPPG-4 inhibitor )

• used in treatment of diabetes ( and diabetic weightloss)

Question 14

What is first phase insulin release ( FPIR )?

Answer 14

Normal glucose tolerance vs type 2 diabetes response

Question 15

Describe the structure of the glucose receptor?

Answer 15

Once insulin binds to extracellular alpha subunit domain = conformational change in tyrosine kinase domains of beta subunit