Glucose Homeostasis Flashcards
Importance of glucose
Glucose is an important energy substrate
Particularly imp for CNS
Threshold leaves for glucose
If glucose level falls below normal levels of 4-5 mmol/L ( hypoglycaemia) , then cerebral function is increasingly impaired
If blood glucose concentration is less than 2 mmol/L , unconsciousness, coma and ultimately death can occur
Persistent hyperglycaemia results in
Diabetes mellitus
Hormone that is hypoglycaemia
Insulin
Hormones that are hyperglycaemic
Glucagon
GH
Cortisol
Catecholamines
Which is the more prevalent form of diabetes
Type 2 Diabetes
What kind of structure is the pancreas gland
Retroperitoneal structure
What are the two types of cells in the pancreas
Exocrine acinar cells
Islet of Langerhans
Pancreas
Most of pancreas generates exocrine secretions via duct to small intestine via the acinar cells - 98% of secretions including protease, amylase and lipas
Other clumps of cells are islets of langerhans but receive 10-15% of blood supply
Types of cells in the islets of langerhans
Alpha cells (20%) which secretes glucagon Beta cells (60%) insulin Delta cells (10%) somatostatin
Two types of junctions in the islets of langerhans
Gap junctions and tight junctions
Gap junctions allow small molecules to pass directly between cells
Tight junctions create small intercellular spaces
Paracrine and endocrine communication between islet cells
What does insulin do
Stimulates growth and development and reduces blood glucose ( stimulates growth via IGF )
What does glucagon do
Increases blood glucose
What does somatostatin do
It inhibits both insulin and glucagon - negative feedback
What happens when there is an increase in blood glucose on Beta cells
Glucagon +
GI hormones +
Increased plasma glucose +
Amino acids +
Sympathetic nervous system inhibits via a2 adrenoreceptors -
Somatostatin -
Parasympathetic stimulate toon enhances rate of insulin release
All act on B cells to release insulin
What does insulin then do
Causes
Build up of glycogen stores
Breakdown of glucose
Increased uptake of glucose into cells by GLUT4
Increased protein synthesis
Reduction of breakdown of fat
Reduction in blood glucose on alpha cells
What stimulates alpha cell secretion;
Parasympathetic nerve activity Amino acids Decreased plasma glucose Some GI hormones CCK SNS activity PNS activity
What inhibits the alpha cells secretion
Insulin
Somatostatin
Effects of glucagon release
Increased gluconeogenesis by liver from amino acids
Increased glycogenolysis by liver
Increased lipolysis for gluconeogenesis
Glucokinase and the stimulation of insulin release
Glucose binds to glut 2
Glucose phosphorylated to Glucose 6-P by glucokinase which is then used to produce ATP
ATP inhibits voltage gated potassium channel and so depolarisation occurs and calcium enters the beta cells and this stimulates insulin release
Insulin and C peptide
Insulin is stored as pro insulin and when proteolytically cleaved, it forms C peptide and insulin
What is the incretin effect
Gut hormones Secreted in response to nutrients in gut Stimulates insulin and suppresses glucagon Increases satiety Useful in treatment of diabetes
Insulin receptor
2 extra cellular alpha subunits
2 intra cellular beta subunit
Once insulin binds to alpha subunit there is a conformational change in the tyrosine kinase domains of beta subunits which undergo auto phosphorylation together with cellular proteins. This leads to the insertion of GLUT4 into the plasma membrane in the intracellular vesicles
