insulin/diabetes Flashcards
what is insulin produced by
islet of langerhans in pancreas
what are islet of Langerhans
cluster of endocrine cells scattered throughout the pancreas
what is insulin
small protein, peptide hormone, two peptide chains, stored as granules
structure of insulin
2 peptide chains
what synthesises insulin
beta cells as proinsulin
when is insulin released
as response to high blood glucose levels
other stimuli of insulin:
amino acids, fatty acids, parasympathetic nervous system, peptide hormones
what is insulin stored as
hexamers
what is a hexamer
3 dimers associating to form a hexamer stabilised by 2 zinc ions
what is a dimer
2 insulin molecules bonded by hydrogen bonds
what do hexamers precipitate to form and the effects of it
precipitates to form crystals, increases stability and protects against proteases
what is the process of insulin release
glucose enters beta cells
glucose metabolised
increase ATP/ADP intracellular ratio
K+ channels close
cell membrane depolarisation
voltage dependent Ca2+ channels open
Ca2+ influx
exocytosis of stored insulin
what is type 1 diabetes
no release of insulin
what is type 2 diabetes
early stages not enough is produced, later stages no response from cells
what is insulin inhibited by
low blood glucose and somatostatin
what is somatostatin
peptide hormone
what is somatostatin produced by
delta cells, hypothalamus, GIT
functions of insulin
promotes cell proliferation/tissue growth/development, promotes cell uptake of K+ and Ca2+, promotes uptake and storage of glucose/amino acids/fats after meals for fuel conservation
anabolic action of insulin
mainly on liver, muscle and adipocytes via insulin receptors to decrease glucose levels
what is anabolic action
mechanism of bonding smaller units together to make a bigger structure
what is an insulin receptor
tyrosine kinase receptor, preformed dimer
what are the relay proteins for insulin receptor called
IRS, insulin receptor substrate
how does glucose enter cells
transporters
what are glucose transporters
solute linked carriers of membrane transport
two types of solute linked carrier/ glucose transporters
GLUT transporters (SLC2 family), sodium-glucose linked transporters (SLC5 family)
what does uniporter mean
transports in one direction
where is GLUT-1 and GLUT-3 mainly expressed
blood brain barrier
where is GLUT-2 expressed
gut, liver, kidney, beta cells
describe GLUT-2 transporters
low affinity, high capacity transporter, transport rate dependent on glucose conc, works in both directions in the liver
where are GLUT-4 expressed
adipocytes and muscles, intracellular location if low insulin levels, translocate cell membrane under insulin action
what are SGLT transporters
secondary active symporter transporters, indirectly require ATP, acts in partnership with GLUT-2
where are SGLT transporters expressed
lumen side of intestinal and renal epithelial cells
structure of glucagon
single chain peptide hormone
where is glucagon synthesised
alpha cells and upper GIT
what stimulates glucagon to be released
low blood glucose/amino acids/para/sympathetic nervous system
what inhibits the secretion of glucagon
somatostatin, high blood glucose, fatty acids
glucagon works via what receptor
glucagon receptor
name other regulators of blood glucose levels
incretins, hormones- adrenaline, growth hormone, glucocorticoids
what is incretin secreted by
endocrine cells of GIT when digested food reaches duodenum
main effect of hormones like adrenaline, growth hormones and glucocorticoids
increase blood glucose
what stimulates adrenaline, growth hormones and glucocorticoids
hypoglycaemia (low blood sugar)
what is diabetes mellitus
chronic metabolic disorder characterised by high blood glucose concentration (hyperglycaemia)
what causes diabetes mellitus
insulin deficiency (type 1), impaired insulin secretion and insulin resistance (type 2)
what is glycosuria
glucose in urine
what is diuresis
increased urine production
symptoms of diabetes melllitus
glycosuria (glucose in urine), diuresis (more pee), dehydration, thirst, fatigue, blurred vision, infections
effects of diabetes mellitus
ketoacidosis (diabetic coma), mainly in type 1 patients, production of ketone decreases pH causing nausea/vomiting/breathlessness/loss of consciousness
effects of ketoacidosis
production of ketone bodies by liver from fatty acid breakdown decreases pH causing nausea/vomiting/breathlessness/loss of consciousness
long term complications of diabetes
deterioration of blood vessel and nerves, damaged blood vessels in eyes lead to losing sight, higher risk of heart attack and stroke, nerve damage in lower limbs lead to cramps/numbness/loss of sensation, wounds take longer to heal, tissue dies, amputation
difference between the cause of type 1 and 2 diabetes
type 1- autoimmune disease
type 2- obesity
treatment of type 2 diabetes
weight loss, oral drugs, insulin injections
auto immunity of type 1 diabetes
progressive destruction of beta cells
treatment of type 1 diabetes
insulin injections, islet transplant
what causes type 2 diabetes
obesity, elevated fatty acids in plasma cause insulin secretions and down regulation of insulin receptors
main side effect of insulin treatments
hypoglycaemia
what is human insulin made by
recombinant DNA technology
why different formulations of insulin treatments and name them
to achieve different peak of effect and duration of action
soluble insulin- rapid/short effect
insulin suspension- delayed/prolonged effect
other (older) drugs for type 2 diabetes
biguanides- increases glucose uptake in muscles and reduce glucose production in liver, advantages doesnt cause hypoglycaemia
sulfonylureas
glitazones
a-glucosidase inhibitors
name a newer drug for type 2 diabetes
sodium glucose co-transporter 2 inhibitors- inhibits SGLT2 in renal proximal tubule, decrease glucose reabsorption, increases urine excretion, high risk of ketoacidosis
gdipeptidylpeptidase-4 inhibitors- inactivate enzyme that degrades GLP1, increase insulin secretion
disadvantage of using sodium glucose cotransporter 2 inhibitors
high risk of ketoacidosis
pharmacological targets for developing drugs
glucagon receptor, free fatty acid 1, glycogen synthase kinase 3, transporter proteins, proteases, growth factors etc.
