The Endocrine Pancreas And Diabetes Melitus Flashcards
Describe the endocrine function of the pancreas
The endocrine functions of the pancreas are performed by the islets of Langerhans. These are small spherical structures which contain around 6000 cells and are found scattered throughout the exocrine tissue.
A typical islet contains a number of cell types that produce different polypeptide hormone. Major cell type are the beta cells that produce insulin (75%) ad the alpha cells that produce glucagon (20%). They store their hormonal products intracellularly
How does the ultra structure of the beta can relate to synthesis and storage of insulin
DNA in Beto cell is transcribed into mRNA. This is ten translated into preproinsulin. This is converted to proinsulin
Explain how insulin is secreted
Glucose in the blood is transported to the beta cells by the glut transporter. This stimerais glycolysis and the TCA cycle. This produce ATP which is used to keep the potassium ion channel closed. The build up of potassium ions causes the cell to be depolarsed which causes the calcium ion charnels to open. The calcium entry trigger exocytosis and insulin is secreted
Explain the modulators of insulin release
Stimulators
Increased plasma glucose, Increase amino acids, Increased free fatty acids.
Hormones include GIP, Gastrin, Glucagon, Secretin, CCK, Adrenaline (at a beta receptors) Parasympathetic nervous system
Inhibitors
Decreased plasma glucose, decreased plasma amino acids, decreased plasma free fatty acids.
Hormones include Somatostatin, Leptin, Adrenaline (at a alpha receptor). Sympathetic nervous system
How does insulin exert its effect on cells
Insulin binds to te insulin receptors. Receptor auto-phosphorylation. Recruitment and activation of signalling complexes at cell membrane. Effects on metabolic pathways and glucose uptake
What are the 3 main target tissues of insulin
- Liver: Activates glycogenesis, Lipogenesis, Glycolysis. Inhibits Glycogenolysis, gluconeogenesis, lipolysis.
- Muscle: Activates glucose uptake (GLUT4), Lipogenesis, Glycogenesis, Glycolysis, Protein Synthesis, Amino acid Transport. Inhibits Lipolysis, Protein catabolism
Adipose tissue: Activate Glucose uptake (GLUT4), Lipogenesis, Glycolysis. Inhibits Lipolysis.
Insulin dominates in fed state metabolism. Actions are anabolic.
Explain glucagon sunthesis
DNA is transcribed into mRNA which is then translated to preproglucagon. This is then converted to pro glucagon n signal peptide cleavage. Progulacagon, is converted to glucagon by proteolytic processing.
Synthesis is similar to insulin where peproglucagon is initially cleaved to form proglucagon. Proglucagon however is more complex containing several peptide hormones.
Explain the control of glucagon release
Similar mechanism to insulin involving potassium ATP channels.. However, in alpha cells potassium channels close in response to a fall in glucose/ATP concentration (in beta cells they close in response to a rise in ATP. Depolarisation of cell membrane opens voltage-gated calcium ion channels allowing infux of calcium ions triggering exocytosis of glucagon from vesicles.
How does glucagon exert its effect on cells
Glucagon binds to the glucagon receptor. G-protein activation. That leads the effector protein activation, then a 2nd messenger. There are effects on metabolic pathways and gene expression.
List the main differences between type 1 and type 2 diabetes
Type 1 diabetes - Absolute insulin deficiency caused by autoimmune destruction of pancreatic beta cells in genetically susceptible individuals.
Type 2 diabetes - Relative insulin deficiency caused by insulin resistance (cells respond less well to insulin). Beta cells eventually wear out from overproduction.
Describe the condition of Diabetes Mellitus
Diabetes mellitus is a group of metabolic disorders characterised by chronic hyperglycaemia (elevated blood glucose concentration), due to insulin deficiency, insulin resistance, or both. There are 2 major types of the disease:
- Type 1 diabetes
- Type 2 diabetes
Describe and explain the typical pattern of presentation of Type 1 and Type 2 diabetes
Type 1 diabetes
- Commonest type in the hound
- Characterised by the progressive loss of all or most of the pancreatic beta cells
- Is rapidly fatal if not treated
- Must be treated with insulin
Type 2 diabetes
- Affects a large number of usually older individuals
- Characterised by the slow progressive loss of beta cells along with disorders of insulin secretion and tissue resistance to insulin.
- May be present for a long time before diagnosis
- May not initially need treatment with insulin but sufferers usually progress to a state where they eventually do
Explain the sequence of events leading to ketoacidosis in the uncontrolled diabetic
Lack of insulin causes decreased uptake of glucose into adipose tissue and skeletal muscle. High blood glucose leads to an appearance of glucose in urine. If not dealt with urgently, it can progress to a life-threatening crisis (diabetic ketoacidosis).
High rates of beta oxidation of fats in the liver coupled to low insulin ratio, means the production of a lot of ketone bodies. Acetone which is volatile can be breathed out and smelt on patients breath. As the ketones develops, the protons on the ketones produce metabolic acidosis (keto-acidosis). Features include: prostration, hyperventilation, nausea, vomiting.
Triad of hyperglycaemia, ketonemia and acidosis.
Explain the triad of symptoms in patients with type 1 diabetes
- Polyuria: Excess urine production
- Thirst (polydipsia drinking a lot): due to excess water loss and the osmotic effect of glucose on the thirst centres
- Weight loss as fat and proteins are metabolised by tissues because insulin is absent
Explain the causes and consequences of hyperglycaemia and hypoglycaemia.
Acute complications of hyperglycaemia
- Metabolic decompensation
- Diabetic ketoacidosis in type 1
- Hyperosmolar non-ketones syndrome in type 2
- Multiple causes of the above complications
Acute complications of hypoglycaemia
- Coma
- Brain needs glucose
- Caused by hypoglycaemic therapy
