Diabetes Flashcards
Where is Insulin produced and excreted from?
What’s it’s normal role?
B-cells in islets of langerhans in endocrine pancreas
Secreted when blood glucose levels increase (after a meal) to allow excess glucose into the cell
Also stimulates glycogen synthase to allow conversion of glucose into glycogen for storage
What’s the mechanism of glucose-activated Insulin secretion?
Extracellular glucose transported into B-cell by GLUT2
Glucose metabolised, increasing ATP release and closure of ATP-dependent K+ channels = cell depolarisation
Voltage gated Ca2+ channels open causing influx and release of insulin by exocytosis
Insulin stimulates fusion of vesicles expressing GLUT4 transporters to the cell membrane
Define Diabetes Mellitus
Complex metabolic disorder characterised by high blood glucose levels due to either insufficient insulin secretion or resistance to action of insulin
Where is glucagon secreted from and under what conditions?
What’s it’s role?
A-cells in islets of langerhans of pancreas by hypoglycaemia
Stimulates gluconeogenesis and glycogenolysis
Liver provides majority of glucose from gluconeogenesis and glycogenolysis during a fasted state
What effects does the nervous system have on glucose homeostasis?
ANS secretes adrenaline which inhibits insulin and stimulates glucagon - directly innervated pancreatic islet cells
SNS releases NA to stimulate glucagon release
PNS stimulates insulin secretion
Cortisol and growth hormones stimulate gluconeogenesis over several hours
Outline Type 1 Diabetes
Autoimmune destruction of B-cells = deficiency in insulin production (associated with other autoimmune conductions eg thyroid disorders/coeliac)
Body is unable to take glucose into cells and cannot store for when needed
Treated only with Insulin
Outline Type 2 Diabetes
Insulin release -> hyperinsulinaemia -> loss of phase 1 insulin response -> B-cell exhaustion -> insulin resistance
Associated with risk factors: overweight, poor diet, apple shaped, smoking, ethnicity, age>40, PCOS
Treatment: modify lifestyle and diet, hypoglycaemic agents to reduce amount of glucose being made in liver (metformin)
What are the complications of Diabetes Mellitus?
Hypoglycaemia by over management
Diabetic neuropathy
Ketoacidosis = ketones produced as alternative energy source from fatty acid metabolism - medical emergency
Increased risk of ischaemic heart disease
Signs of diabetic ketoacidosis?
Shock
Dehydration
High resp rate
Abdo pain - often first symptom with type 1 diabetic who forgets medication
Symptoms of Diabetic Mellitus?
Hyperglycaemia (loss of insulin secretion, inability to uptake glucose into cells, cannot store it as glycogen)
Polyuria - increased urination (glycosuria as kidney unable to reabsorb)
Polydipsia - excessive thirst (physiological response to dehydration from fluid loss and hyperglycaemia directly stimulates thirst centres)
Weight loss (unopposed lipolysis and proteolysis)
Where’s glucose available from?
Diet
Breakdown of glycogen - glycogenolysis
Formation of glucose - gluconeogenesis
How does glucose get into cells?
Hydrophillic so will diffuse very slowly
Uses specific transporters GLUT1 - GLUT4 facilitated diffusion
SGLT1 and SGLT2 uses Na+ to move glucose against gradient
What are the 3 major cell types in the endocrine pancreas?
a - glucagon
b - insulin
D - somatostatin (inhibits insulin and glucagon)
What’s biphasic insulin secretion?
Insulin secretion occurs in 2 phases
1st phase has rapid onset lasting 10 mins (release of pre-docked primed vesicles)
2nd phase is prolonged plateau for as long as hyperglycaemia exists
What’re the actions of Insulin?
Insulin promotes fusion of vesicles containing GLUT4 to the cell wall, allowing glucose uptake
Also promotes glycogen synthase for glycogen synthesis of excess glucose
Promotes protein synthesis and inhibits protein breakdown
Promotes lipogenesis and inhibits lipid breakdown
What regulates Glucagon secretion?
Hypoglycaemia stimulates release from a-cells in pancreas
Insulin secretion suppresses glucagon secretion/action and release is also inhibited in hyperglycaemic conditions
What are the roles of glucagon?
Stimulate gluconeogenesis and glycogenolysis
Increase hepatic fatty acid oxidation and ketone body formation (for energy)
Stimulate lipolysis in adipose cells and inhibit their uptake of glucose
What role do cortisol and growth hormones have on glucose homeostasis?
Promote gluconeogenesis and inhibit glucose transport
Cortisol directly inhibits Insulin secretion
What’s the effect of the sympathetic nervous system on glucose regulation?
Adrenaline inhibits Insulin secretion and promote Glucagon release
Directly innervates pancreatic islet cells (PNS has opposite effect)
According to the WHO what are the 4 classifications of blood sugar levels?
Normal
Impaired fasting glycaemia
Impaired glucose tolerance
Diabetes
What’s ketoacidosis? What are the 3 main ketones?
Ketone bodies used as alternative energy source
Acetone, Acetoacetate and B-hydroxybutyrate
Lead to acidaemia - emergency, seen predominantly in type 1 diabetes
What are complications of DM?
Hypoglycaemia due to treatment
Microvascular: nephropathy, neuropathy, retinopathy
Macrovascular: ischaemic heart disease, cerebrovascular disease peripheral vascular disease
