RED Endocrine 2 Learning objectives PDF

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Summary

1. Describe the composition of cell types within pancreatic islet and statetheir hormone productsExocrine - pancreatic enzymes - break down carbohydrates, proteins and lipids in the chymeEndocrine - i slets of Langerhans - clusters of endocrine cells scattered throughout the pancreasAn Islet cell co...

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1. Describe the composition of cell types within pancreatic islet and state their hormone products Exocrine- pancreatic enzymes- break down carbohydrates, proteins and lipids in the chyme Endocrine- islets of Langerhans- clusters of endocrine cells scattered throughout the pancreas

An Islet cell consists of Alpha (secretes glucagon) Beta ( secrets insulin) Delta (secretes somatostatin) PP ( secretes pancreatic polypeptide) epsilon cells which secrete ghrelin

2. Briefly describe the steps involved in the biosynthesis of insulin 1. The insulin gene is transcribed into mRNA inside the nucleus of the cell, the mRNA is a large precursor known as the preproinsulin 2. The preproinsulin has the presignal peptide which is cleaved as the peptide travels through the stac of the RER and is now proinsulin 3. Proinsulin undergoes folding and is transported by microvesicles to the golgi body from the RER 4. Cleavage of the C peptide on proinsulin occurs to give rise to insulin which consists of the A and B chain and 3 disulphide bridges. There are 3 enzymes involved in the cleavage PC1 PC2 CP 5. Now the peptide is less water soluble and therefore starts to precipitate out with zinc ions. For every 2 zinc ions there are 6 insulin molecules. This produces a crystalloid core of packed insulin inside the secretory granules 6. When required the insulin is released by exocytosis which needs energy from ATP and calcium ions

3. Outline the control of insulin and glucagon secretion – including effects of nutrients, autonomic innervation and intrapancreatic paracrine effects Insulin secretion

1. Nutrient stimuli- the main physiological regulator is Glucose

Once blood glucose is higher than 5mmols there is a rise in the ATP:ADP ratio and this results in closer of the ATP sensitive K+ channels. This causes membrane depolarisation and the opening of voltage gated calcium channels which then promote insulin release. At rest the ATP sensitive K+channels are open causing potassium efflux out of the cell and therefore hyperpolarisation. The voltage gated calcium channels are closed and therefore there is only a low rate of insulin release. This results in a basal level of insulin release and low blood glucose levels

2. Potientiators More insulin is released due to the effect of incretins as they potentiate and induce insulin release as they prime the Beta cells to make more insulin once glucose is sensed in the mouth. Gut hormones are an anticipatory response to a marked increase in glucose when food susbtances are consumed in the mouth

3. Neural control Parasympatheic system rest and digest- there is more insulin release once there is stimulation of muscarinic receptors Sympathetic- there is less insulin release once there is stimulation of alpha 2 adrenoceptors but more release with Beta adrenoceptor stimulation Glucagon release is stimulated by low blood glucose levels and by the para and sympathetic nervous system as well as amino acids.

4. Describe the steps involved in glucose-induced insulin secretion 1. At higher levels of glucose ( 5mmols) there is a change with the ATP:ADP ratio and more ATP is being made 2. This change in ratio closes the ATP sensitive K+ channels causing less potassium efflux 3. This makes the cell more positive and the membrane becomes depolarised allowing the voltage gated calcium channels to open 4. The high levels of calcium then allow more exocytosis of insulin

5. State the effects of insulin on glucose uptake and glucose utilisation in key target tissues, state the anabolic effects of insulin Insulin action:    

Promote growth & development + + + Promote cellular uptake of K via Na /K -ATPase pump Promote uptake & utilisation of glucose in skeletal muscle & adipose Promote fuel storage (ANABOLIC)

-  rate of synthesis and storage of energy reserves (glycogen & fats) and of protein Insulin action is to reduce blood glucose, and this is done in ay ways In the Muscle :   

There is increased glucose uptake Increased protein synthesis Decreased protein breakdown

In the adipose tissue:   

Increased glucose uptake Increased lipogenesis Decreased lipolysis

In the liver:   

Increased glycogen synthesis Decreased glycogen breakdown Decreased gluconeogenesis

6. Briefly describe insulin receptor signalling 1. Insulin binds to the tyrosine kinase receptor which is a dimer and this activates intrinsic tyrosine kinase activity 2. Get auto phosphorylation of the receptor 3. Adaptor proteins then recognise the phosphorylated receptor and themselves then become phosphorylated 4. This then produces multiple signals including the growth signal and the metabolic signal 5. The growth signal causes cell proliferation and cell survival 6. The metabolic signal causes glucose uptake, protein synthesis, glycogen synthesis and anti-lipolysis

7. Describe the roles played by insulin and the counter-regulatory hormones (glucagon, adrenaline, cortisol and growth hormone) in glucose homeostasis (see later lectures) Insulin – high levels of blood glucose stimulate the Beta cells to produce and release more insulin to lower blood glucose to normal. Increased glucose utilisation in adipose and skeletal muscle. Decreased glycogenolysis and gluconeogenesis

Glucagon- low levels of blood glucose stimulates the Alpha cells to produce and release more glucagon to increase blood glucose to normal. Increased gluconeogenesis and glycogenolysis Adrenaline or NA- Decreased glucose utilisation in adipose and skeletal muscle. Increased gluconeogenesis and glycogenolysis. Think of using up more glucose so there are lower blood glucose levels- severe hypoglycaemia Cortisol- Decreased glucose utilisation in adipose and skeletal muscle. Increased gluconeogenesis. Think of using up more glucose due to stress so there are lower blood glucose levels Growth hormone- Decreased glucose utilisation in adipose and skeletal muscle. Increased gluconeogenesis. Think of using up more glucose due to growth and development so there are lower blood glucose levels Somatostatin- inhibits effects of insulin and glucagon...