endocrine pancreas, Diabetes Mellitus Flashcards
what cells make up the Islets of Langerhans?
α cells
β cells
δ cells
PP cells
what do α cells secrete?
glucagon
what do β cells secrete?
Insulin and Amylin
what do δ cells secrete?
Somatostatin
what do PP cells secrete?
Pancreatic Polypeptide
what is insulin?
polypeptide hormone with 2 amino acid chains
how are the 2 amino acid chains of insulin liked?
2 disulphide bonds
how is insulin secretion regulated?
Insulin secretion is tightly regulated and is controlled by blood levels of various nutrients, neural stimulation and hormones.
what is the principle stimulus to insulin secretion?
glucose
what are the endogenous factors controlling insulin secretion?
incretins
GIP: glucose-dependent insulinotropic peptide
GLP-1: glucagon-like peptide-1
where is insulin released into?
into the portal vein
what is the half life of insulin in plasma?
5-6 minutes
what is the half life of proinsulin in plasma?
17 minutes
what is the half life of C peptide in the plasma?
30 minutes
How does the degradation of insulin occur?
Proteolytic degradation of insulin occur mainly in liver, kidney & muscle usually after internalisation of insulin
what is the main hormone in controlling metabolism of carbohydrate, fat and protein?
insulin
what is the most obvious cause effect of insulin?
reduce the blood glucose and is the only hormone capable of reducing blood glucose level.
what are long term effects of insulin?
Increase & decrease of key enzymes &
Stimulates cell proliferation
what are the effects of insulin on the liver?
Increased glycogen synthesis (↑glycogenesis)
Increased use of glucose for the energy (↑glycolysis)
Increased fat synthesis (↑lipogenesis)
Decreased synthesis of ketone bodies (↓ketosis)
what metabolic process of the liver does insulin decrease?
ketosis - synthesis of ketone bodies
what are the actions of insulin on fatty tissues?
Increased glucose uptake
Increased fatty acid uptake
Increased fat synthesis
Increased glycolysis
what are the actions of insulin on muscle?
Increased glucose uptake
Increased uptake of amino acids
Increased glycogenesis
Increased glycolysis
what is glucagon?
Single chain peptide of 29 amino acids synthesized by α cells of pancreatic islets.
what is the main physiological stimuli of glucagon?
amino acids in plasma
Do high or low concentrations of fatty acids and glucose stimulate glucagon secretion?
low concentrations
Do high or low concentrations of fatty acids and glucose inhibit glucagon secretion?
high concentration
how does somatostatin impact glucagon release?
Somatostatin inhibits glucagon release
how do catecholamines and cholinergic impact glucagon release?
Catecholamines & cholinergic stimulation both increase glucagon release
what is the half life of glucagon?
3-6 minutes
where is the primary site of action for glucagon?
liver
where does glucagon increase glycogenolysis?
liver
where does glucagon increase gluconeogenesis?
liver and kidney
where does glucagon reduce glycogen synthesis?
liver
where does glucagon reduce glucose oxidation?
liver
where does glucagon increase lipolysis?
liver and fat
where does glucagon increase ketogenesis?
liver
where does glucagon reduce lipogenesis?
liver
where does glucagon increase proteolysis?
liver
what is amylin?
37 amino acids peptide co-stored with insulin and release with insulin by β-cells
what is the function of amylin?
Complement insulin action by reducing gastric emptying, antagonizing glucagon effects and reducing food intake
what is function of somatostatin?
Inhibits insulin & glucagon release.
Inhibits growth hormone & TSH release from pituitary
inhibits release of various GI hormones
how can diabetes mellitus be characterised?
hyperglycaemia - raised blood glucose level
what is the normal range of blood glucose levels?
3.5 - 7 mmol/L
how is normal glucose levels reached in a fasting state?
decreased blood glucose –> release of glucagon –> glucagon action
how is normal glucose levels reached after a meal?
increased blood glucose –> release of insulin from the pancreas –> insulin action
what are the 2 types of diabetes mellitus?
type 1 or insulin dependent diabetes mellitus
type 2 or non-insulin dependent diabetes mellitus
what is the pathophysiology of Type 1 diabetes?
beta cells of pancreas which produce insulin are completely destroyed
what is the pathophysiology of Type 2 diabetes?
beta cells produce too little insulin too late
tissue responses to insulin may also be decreased (Insulin resistance) especially in overweight people
what are the 3 classic symptoms of diabetes?
polydipsia (extreme thirst)
polyuria (excessive urine output)
feeling tired and lethargic
what are some other symptoms of diabetes?
Genital itching
Fluctuating vision,
Night cramps
Weight loss (particularly in type 1)
why do polydipsia and polyuria occur?
high blood glucose –> glucose in urine –> loss of water with glucose loss –> increased urine output –> dehydration/increased serum osmolality –> extreme thirst
what are the tests conducted for the diagnosis of diabetes?
blood glucose level
presence of glucose in the urine
when is a diagnosis of diabetes made?
Fasting plasma glucose ≥ 7 mmol/L and/or
Random plasma glucose ≥ 11.1 mmol/L
what are the acute metabolic complications associated with diabetes?
Ketoacidosis (Type 1)
Non-ketotic Hyperosmolar Hyperglycaemic State (Type 2)
Hypoglycaemia
what are the microvascular long term complications associated with diabetes?
retinopathy (Damage to retina)
neuropathy (Nerve damage)
nephropathy (Kidney damage)
what are the macrovascular long term complications associated with diabetes?
Diabetes is a risk factor for
heart attack
stroke
decreased blood circulation leading to gangrene (e.g. foot)
what are the clinical features of ketoacidosis?
Thirst Polyuria Vomiting Hyperventilation Weakness Confusion & Coma
what is the treatment for ketoacidosis?
Fluid, insulin and potassium in hospital
when does non-ketotic hyperosmolar hyperglycaemic state (HHS)?
Occurs in people with Type 2 diabetes, who may be experiencing very high blood glucose levels (often over 40mmol/l)
how fast is the development of HHS -?
usually develops over a course of weeks
what are the clinical features of non-ketotic hyperosmolar hyperglycaemic state?
Thirst Polyuria Weakness Confusion & Coma But no ketoacidosis, so no hyperventilation
what is hypoglycaemia?
Blood glucose <4 mmol/L
when can hypoglycaemia occur?
Major source of anxiety for insulin treated diabetic patient
Could also occur in patients treated with insulin secretagogues such as sulphonylureas
what are the autonomic signs and symptoms of hypoglycaemia?
Anxiety, tremor, palpitations, sweating etc.
what are the neuroglycopenic signs and symptoms of hypoglycaemia?
Dizziness, blurred vision, headache, tiredness, inability to concentrate, hunger, shivering etc.
what are the aims of diabetes management?
alleviate symptoms
prevent acute metabolic complications
prevent long term complications
what are some ways to manage diabetes?
Patient education
Control of diet
Drug therapy
Detection & treatment of early signs and symptoms of long-term complications
what are some antidiabetic drugs?
sulphonylureas, biguanides
what are examples of sulphonylureas?
Chlorpropamide, Glibenclamide, Gliclazide, Glimepiride, Glipizide & tolbutamide
what are examples of biguanides?
Metformin
what are the type of insulins used?
Short-acting insulins
Intermediate- and long-acting insulins
what is the mode of action for sulfonylureas?
stimulate insulin secretion from beta cells
what are side effects of sulfonylureas?
Weight gain . Hypoglycaemia GI disturbances Sensitivity reactions Facial flushing with Chlorpropamide
what is the mode of action for biguanides?
Increases glucose uptake by peripheral tissue
Reduces hepatic gluconeogenesis
Reduces appetite
what are side effects of biguanides?
GI disturbances
Weight loss (useful in overweight patients)
Lactic acidosis (should not be given to patients with renal disease or severe pulmonary or cardiac disease )
Decreased Vitamin B12 absorption
why doesn’t Hypoglycaemia occur with metformin?
it has no effect on insulin secretion
what is the mode of action for acarbose?
delays the digestion and absorption of starch & sucrose by inhibiting alpha glucosidase enzymes
what are the side effects of Acarbose?
Flatulence .
Abdominal distention or pain, diarrhoea
what is the mode of action for meglitinides?
Stimulate insulin secretion from pancreas which is claimed to be glucose dependent
what are the side effects of meglitinides?
Weight gain
Hypoglycaemia
GI disturbances
sensitivity reactions
what is the mode of action for thiazolidinediones/glitazones?
PPARγ agonists
what are the side effects of Thiazolidinediones or glitazones?
Pioglitazone should not be used in patients with heart failure or history of heart failure
what is the mode of action for Dipeptidylpeptidase-4 Inhibitors?
Inhibitor of DPP-4 inhibitor; DPP-4 break down endogenous incretins GIP and GLP-1
what is the mode of action for incretin mimetic drugs?
Peptide GLP-1 receptor agonists Glucose dependent stimulation of insulin secretion Inhibits glucagone secretion Delays stomach emptying Promote weight loss
what are the side effects of incretin mimetic drugs?
Nausea, vomiting and diarrhoea
Can cause hypoglycaemia when combined with sulphonylureas
what is the mode of action for sodium-glucose co-transporter 2 (SGLT2) inhibitor?
improves both fasting and post-prandial plasma glucose levels by reducing renal glucose reabsorption leading to urinary glucose excretion
what are the side effects of sodium-glucose co-transporter 2 (SGLT2) inhibitor?
Urinary tract infections
what are the sources of Insulin treatment?
beef, pork but mainly human (by recombinant DNA technology)
what are the short acting insulins?
Soluble insulin
Insulin aspart
Insulin glulisine
Insulin lispro
what are the intermediate- and long-acting insulins?
Isophane
Insulin detemir, Insulin glargine
Protamine zinc insulin
what are the 3 types of insulin preparations?
short acting insulins
intermediate- and long-acting insulins
biphasic insulins
what are some examples of normal insulin regimens?
Short-acting insulin mixed with intermediate-acting insulin: twice daily (before meals);
Short-acting insulin mixed with intermediate-acting insulin: before breakfast
Short-acting insulin: before evening meal
how is diabetes monitored?
blood glucose levels, urine glucose, urine ketones, blood pressure, lipid profile, obesity, smoking
what are some programmes and help available to prevent long-term complications of diabetes?
Such as retinal screening
Screening for microalbuminuria
Foot care from Chiropodist etc.
