Endocrinology 4 - Insulin secretion Flashcards
What is the hormone involved with lowering blood glucose?
Insulin.
What are the hormones involved with increasing blood glucose? (4)
- Glucagon.
- Somatotrophin.
- Catecholamines.
- Cortisol.
What are possible complications of diabetes? (4)
- Diabetic retinopathy (affects vision).
- Nephropathy (kidney disease).
- Heart attacks.
- Stroke.
Why is glucose important?
- Very important energy substrate especially for CNS.
2. Very low blood glucose levels (below 2mM) could lead to coma and death.
What is 98% of the pancreas associated with? And the remaining 2%?
98% - Exocrine secretions via a duct to the small intestine.
2% - Endocrine = islets of Langerhans.
What are Islet of Langerhans made of? And what do each of the cells release? (3)
- Alpha - Glucagon.
- Beta - Insulin.
- Delta - Somatostatin.
What increases insulin secretion? (6)
- Increased blood glucose.
- Certain AA.
- Certain gastrointestinal hormones (Glucagon Like Peptide).
- Glucagon.
- Parasympathetic activity.
- Beta cell receptors.
What decreases insulin secretion? (2)
- Somatostatin.
2. Sympathetic activity.
What are the effects of insulin? (5)
- Decreased lipolysis + increased lipogenesis.
- Increased glycogenesis.
- Increased glycolysis.
- Increased glucose transport into cells via GLUT4.
- Increased AA transport + increased protein synthesis + decreased protein breakdown.
All the above decreases blood glucose levels.
What increases Glucagon secretion? (5)
- Decreased blood glucose levels.
- Certain AA.
- Certain gastrointestinal hormones.
- Sympathetic activity.
- Parasympathetic activity.
What decreases glucagon secretion? (2)
- Somatostatin.
2. Insulin.
What are the effects of glucagon? (3)
- Increased hepatic glycogenolysis.
- Increased lipolysis => increased gluconeogenesis.
- Increased AA transport into liver => increased gluconeogenesis.
All the above increases blood glucose levels.
How is glucose concentration detected by beta cells? (3 steps)
- Glucose enters beta cell via GLUT 2 (not insulin regulated).
- Converted to glucose-6-phosphate by glucokinase (rate determining step).
- The rate of glucose-6-phosphate production determines the rate of insulin production.
How is insulin released by beta cells? (5 steps)
- Glucose enters the beta cell via GLUT 2.
- Converted to G6P by glucokinase.
- ATP porduced blocks ATP sensitive K+ channel on membrane.
- Opens voltage dependent Ca+ channel and Ca+ moves in.
- Exocytosis of stored insulin + production of further insulin.
What is the structure of insulin?
- Constructed as pre-proinsulin - has three chains and signal peptide.
- C peptide and signal peptide are removed to produce insulin (2 chains).
How can you measure the endogenous insulin production of a person?
By measuring the amount of C peptide in the person as the molar ratio of insulin to C peptide is 1:1.
What is the Incretin effect?
Food stimulates more insulin secretion if given orally rather than intravenously.
What is Glucagon Like Peptide-1 (GLP-1)?
- It is a gut hormone that is secreted by L-cells in the gut in response to nutrients.
- It stimulates insulin production and suppresses glucagon.
- It increases the feeling of fullness and has a short half life.
How can T2DM be treated?
DPPG-4 inhibitors prevent the degradation of GLP-1 = makes people feel full for longer.
What is first phase insulin release?
When glucose given intravenously to a normal person they release the stored insulin (large amount) and carry on releasing for two hours.
Do people with T2DM have first phase insulin release?
No. Insulin made later on.
How is insulin detected by cells?
- Insulin binds to alpha subunit of insulin receptor.
- Beta subunit has conformational change and has a metabolic effect inside the cell on glucose, AA and FA.
- Also affects growth (mitogenic pathway).
Is insulin resistance caused by the transmembrane protein not being able to recognize insulin?
No. It involves post receptor cytoplasmic elements of insulin function.
What is Type 1 Diabetes Mellitus?
- Absolute insulin deficiency.
2. Elevated glucose where insulin is required to prevent ketoacidosis.
What is Type 2 Diabetes Mellitus?
- Insulin resistance.
- More prevalent than T1DM and is a considerable health burden.
- It is defined in terms of glucose but can also be related to hypertension and dyslipidaemia.
- Has a significant genetic component although obesity can trigger the onset.
What allows hormones in the pancreas to have an effect on adjacent cells? And what is this effect called?
- Paracrine effect.
2. Gap junctions allow this to happen.
What is first phase insulin release important for?
It is important for switching off liver glucose production.
