Session 7 - Endocrine Pancreas And Diabetes Mellitus Flashcards
What are 4 functions of insulin?
Anti-gluconeogenic
Anti-lipolitic
Anti-ketogenic
Glycogenic
What are 4 functions of glucagon?
Ketogenic
Lipolitic
Gluconeogenic
Glycogenolytic
What are the 6 steps of insulin synthesis?
- Pre-proinsulin synthesized by ribosomes on rough ER
- Signal cleaved becomes proinsulin in ER
- Proinsulin packaged into storage vesicles in trans-Golgi apparatus
- Proteolysis removes C-peptide and breaks proinsulin into insulin - 2 chains held together by disulphide bridge
- Margination - vesicle moves to cell surface
- Exocytosis - vesicle content released
How is insulin stored in beta-cells?
Stored in beta-cell storage granules as crystalline zinc-insulin complex
What is Diabetes Mellitus?
Group of metabolic disorders characterized by hyperglycemia due to insulin deficiency, resistance or both
What are 8 key differences between type 1 and 2 diabetes?
Childhood / middle age Sudden onset / gradual onset Severe / acute symptoms Recent weight loss / no Weight loss Usually lean / obese Ketosis / non-ketotic No C peptide / C-peptide detectable Markers for auto-immunity / no markers for autoimmunity
What is type 1 diabetes?
Progressive loss of all or most of pancreatic beta cells
What is type 1 diabetes caused by?
Genetic predisposition interacts with environmental trigger produces immune activation which destroys beta cells
What are 4 symptoms of type 1-diabetes?
Polyuria Polydipsia Weight loss Glucosuria Acetone breath
What is diabetic ketoacidosis?
High rates of beta oxidation of fats in liver and low insulin leads to production of many ketone bodies, causes keto acidosis which can be fatal
What is type 2 diabetes?
Slow progressive loss of beta cells and disorders of insulin secretion and tissue resistance to insulin
What causes type 2 diabetes?
Genetic predisposition
What are 9 possible symptoms of type 2 diabetes?
Polyuria Polydipsia Weight loss Lethargy Thrush infection of genitalia Infection of feet Poor wound healing Visual problems
How to treat type 1 diabetes?
Insulin injections - appropriate doses and times
Diet and exercise
Frequent blood glucose measurement - glucometer
How to treat type 2 diabetes?
Diet and exercise
Insulin injection
Oral hypoglycemic drugs - sulphonylureas and metformin
How does sulphonylureas treat diabetes?
Increase insulin release from remaining beta cells and reduce insulin resistance
How does metmorfin treat diabetes?
Reduce gluconeogenesis
What is the effect of persistent hyperglycemia?
Abnormal metabolism of glucose by Aldiss reductase which depletes cellular NADPH and increases disulphide bond formation, affecting structure and function. Increased sorbitol also causes osmotic damage
Increased glycation of plasma proteins, affects function
Why measure glycation of haemoglobin?
Glucose in blood will react with terminal valine of haemoglobin to produce glycated haemoglobin, %HbA1c reflects average blood glucose concentration over the past 3 months
What are 3 macro vascular complications of diabetes?
Increased risk of stroke
Increased risk of MI
Poor circulation to the periphery
What are 4 micro vascular complications of diabetes?
Diabetic eye disease - visual problems due to osmotic effects of glucose, retinopathy (damage to blood vessels in retina)
Diabetic kidney disease - damage to glomeruli, poor blood supply due to changes in blood vessels, infections of urinary tract
Diabetic neuropathy - damaged peripheral nerves, causing loss of sensation
Diabetic feet - poor blood supply, damage to nerves, increased risk of infection
What is metabolic syndrome?
Group of symptoms including insulin resistance, dyslipidaemia, glucose intolerance and hypertension associated with central adiposity
What are 2 effects of metabolic syndrome?
Type 2 diabetes
Heart disease