Glucose Homeostasis Flashcards
Why is glucose important?
Glucose is an important energy substrate
Especially for the CNS
Why is glucose so important for the CNS?
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.
How is glucose regulated?
Glucose is closely regulated
Feedback system is needed for this regulation
Persistent hyperglycemia results in diabetes mellitus
What increases blood glucose?
Glucagon
Cortisol
GH
Catecholamines
What decreases blood glucose?
Insulin
What % of people are affected with diabetes mellitus in the UK?
7%
What is the % risk increase risk of a person with diabetes mellitus dying relative to an age-matched control without diabetes mellitus?
34%
How much of the NHS budget is spent on diabetes mellitus?
10%
What is the most prevalent form of diabetes?
Type 2 diabetes mellitus
What are the types of diabetes?
Maturity onset diabetes of the young (MODY)
T1/2DM
what type of structure is the pancreas?
Retroperitoneal structure
What does retroperitoneal structure mean?
Having to do with the area outside or behind the peritoneum
What is the peritoneum?
a membrane, a sheet of smooth tissue that lines your abdominopelvic cavity and surrounds your abdominal organs
What does most of the pancreas generate?
98% generates exocrine secretions via duct to small intestine
What is the rest of the 2% of the pancreas?
Small clumps of cells within pancreatic tissue (remaining 2%) are called islets of Langerhans
How much of the pancreatic blood flow goes to the islets of langerhans?
10-15%
What are the cells in the islets of langerhans and what do they secrete?
alpha cells= glucagon
beta cells= insulin
gamma cells= somatostatin
What are the junctions between the cells in the islets of langerhans?
Tight junctions and gap junctions
What type of communication between islet cells?
Paracrine
What are gap junctions?
Allow small molecules to pass directly between cells
What are tight junctions?
Create small intercellular spaces
How much of the islets are each type of cell?
alpha= 30%
beta= 60%
gamma= 10%
*they are all involved in glucose homeostasis
What are the actions of pancreatic hormones?
Somatostatin inhibits both insulin and glucagon
Insulin decreases blood glucose
Glucagon increases blood glucose
Insulin promotes growth and development
What increases and decreases insulin secretion from B cells when there is an increase in blood glucose?
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
What does insulin cause in liver (7)
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
what promotes and inhibits alpha cells when blood glucoses decreases?
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
How does the liver react to increased glucagon from reduced blood glucose? (4)
Increase AA transport in liver
Increase gluconeogenesis
Increase hepatic glycogenolysis
Increase lipolysis
AA and fatty acid increase=> gluconeogenesis
Is GLUT2 sensitive to insulin?
No
What is the role of glucokinase?
promote glucose-> glucose-6-phosphate
glucokinase= hexokinase IV
what causes cells to secrete insulin?
- glucose enters the cell via GLUT2
- Glucose is converted to glucose-6-phosphate (rate-limiting step) via glucokinase
- Glucose-6-P forms ATP
- this ATP binds to a potassium ion channel and closes it
- intracellular K+ causes calcium ion channels to open allowing Ca2+ to enter the cell
- intracellular shift of calcium leads to release of stored insulin
*none of this process is restricted
How is C-peptide related to insulin?
Proinsulin is made of c peptide and insulin
Via proteolytic cleavage
What is insulin composed of?
A chain and B chain with disulphide bridges between them
What does measuring C peptide help show?
How much insulin your body is making
What are incretins?
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.
What is evidence of a gastrointestinal incretin effect?
food sitting in stomach enhances insulin
What is Glucagon like peptide-1 (GLP-1)?
Gut hormone
- Secreted in response to nutrients in gut
- Transcription product of pro-glucagon gene, mostly from L-cell
What does glucagon like peptide-1 (GLP-1) stimulate and suppress?
Stimulates insulin and suppresses glucagon
What does glucagon like peptide-1 (GLP-1) do?
↑ satiety (feeling of ‘fullness’)
What is the half life of glucagon like peptide-1 (GLP-1)?
Short half life due to rapid degradation from enzyme dipeptidyl peptidase-4 (DPPG-4 inhibitor)
What is glucagon like peptide-1 (GLP-1) used to treat?
diabetes and obesity
What happens during the First phase insulin release (FPIR) during the IV glucose challenge between normal glucose tolerance and type 2 diabetes mellitus?
Describe the insulin receptor?
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
