Flashcards in Session 4 - Can't Diabeat it Deck (34)
What is diabetes characterised as?
It is characterised as chronic hyperglycaemia due to insulin deficiency, insulin resistance or both.
Why does glucose need to be kept in a specific range?
It is vital that Glucose is kept within a lower and upper range. Glucose must be kept above a minimum level to adequately support the CNS, but an excessive amount of it results in damage over time.
What is blood glucose normally maintained at?
What is the normal physiological range for glucose conc in blood?
Rarely stray outside the range of 4.5 – 5.6mmol/LL regardless of food, fasting or exercise
What is the minimum blood glucose conc?
o Plasma glucose concentration of < 2.2mmol/L may result in hypoglycaemic coma and death due to insufficient glucose reaching the brain
What is the maximum glucose before it begins to be excreted in urine?
o Plasma glucose concentration of > 10mmol/L exceeds glucose’s renal threshold, which means glucose will be present in the urine. Osmotic diuresis then occurs.
How do the islets of langerhan detect glucose conc?
What do cells in islets of langerhan secrete, and what cell do what?
vGlucagon (α-cells) and Insulin (β-cells)
What factors other than glucose level can cause release of glucagon and insulin?
- Gastrointestinal hormones
- Autonomic Nerves
Where can glucose receptors be found other than pancreas?
Ventromedial and lateral areas of hypothalamus
What do glucose receptors in the hypothalamus do?
regulate appetite and feeding, and they also indirectly stimulate the release of a variety of hormones, including adrenaline, growth hormone and cortisol, all of which affect glucose metabolism.
What tissue types do I and G target?
Liver, Skeletal Muscle and Adipose tissue
Outline the structure of insulin
Insulin is a 51 amino acid peptide made up of an α-chain and a β-chain, linked by disulphide bonds.
What is the half life of insulin, and what is responsible for its metabolism?
It has a half-life of 3-5 minutes and is metabolised to a large extent by the liver, but also by the kidneys and muscles.
How can we detect endogenous levels of insulin?
Amount of C-peptide in blood, part of cleavage of insulin C-chain during post-transcription processing
What do B cells secrete insulin in response to?
high blood glucose levels, as well as to glucosamine, amino acids, fatty acids, ketone bodies and Sulphonylureas.
What 5 things inhibit insulin release?
low blood glucose concentration, growth hormone, glucagon, cortisol and sympathetic nervous system activation.
What does binding of insulin to IRS on cell surface trigger
Activation of insulin signalling pathway, causing transporter of Glut 4 to be moved from storage vesicles to the membrane.
Other than increased glucose uptake, what are three other effects of insulin on the cell?
What stimulates secretion of glucagon?
Low blood glucose conc
What are the actions of glucagon?
stimulating glycogenolysis and gluconeogenesis in the liver and increasing lipolysis in adipose tissue.
How is insulin stored?
-cells storage granules as a crystalline-zinc complex.
How does insulin circulate?
Dissolves in the plasma and circulates as a free hormone.
What are the three main target tissues of insulin?
Is insulin anabolic or catabolic?
What are the short term effects of insulin?
Clear absorbed nutrients from the blood following a meal
What are the long term effects of insulin?
effects on cell growth/cell division that relate to its ability to stimulate protein synthesis and DNA replication.
Outline the three overarching metabolic effects of insulin
Amino acid metabolism
How does insulin effect carbohydrates?
- Increased glucose transport into adipose tissue/skeletal muscle
- Increased glycogenesis and decreased glycogenolysis in liver/muscle
- Decreased gluconeogenesis in liver
- Increased glycolysis in liver/adipose tissue
How does insulin effect lipid metabolism?
- Decreased Lipolysis in adipose tissue
- Increased Lipogenesis and esterification of fatty acids in liver and adipose tissue
- Decreased Ketogenesis in liver
- Increased Lipoprotein lipase activity in the capillary bed of tissues such as adipose tissue
How does insulin effect amino acid metabolism?
Increased Amino acid uptake and protein synthesis in liver, muscle and adipose tissue
Decreased Proteolysis in liver, skeletal muscle and adipose tissue
Outline the 5 key characteristics of diabetes mellitus
o An absolute or relative insulin deficiency
Autoimmune destruction of pancreatic β-cells
Why is diabetes so clinically important?
Associated with a whole range of macro and microvascular complications.