insulin secretion and intermediary metabolism Flashcards
what is insulin
The hormone of eating
it stores away food and lowers blood glucose
which hormones act to increase glucose
glucagon
catecholamines
somatotrophin
cortisol
what does a diagnosis of diabetes mean to people
in pregnancy - tight control of blood sugar
people worried about hypoglycaemia
what is T1DM
elevated glucose
insulin required to prevent ketoacidosis
insulin needed to maintain life and prevent high sugar affecting kidney function
what is T2DM
more common
health burden
glucose
hypertension and dyslipidaemia
dyslipidaemia and diabetes
major risk factor for CVD
elevated LDL and TG conc
decreased HDL and cholesterol
describe the prevalence of diabetes
T1 11%
T2 85-95%
MODY 3%
obesity can trigger T2DM - not the cause
how is diabetes treated or monitored
diet - alter nutrition
insulin - physiologically - match to meal, complex protein that gastric acid breaks down - injection not tablet
capillary glucose monitoring
insulin pump - doesn’t complete homeostatic loop - still need to measure insulin and carbs
when does hypoglycaemia occur
imbalance between diet, insulin and exercise
out of blue
cause accident
why is glucose important
respiratory substrate - esp CNS
<4-5mM - hypoglycaemia - brain function impaired
<2mM coma
variable between individual and ability to use other substrates
describe the action of insulin on the B cell
stimulates glucose transporter Glut 2
freely allow glucose into the cell so can see glucose conc
glucokinase - rate limiting step - glucose-6-phosphate - met pathways - insulin secretion amount appropriate to ambient glucose concentration
describe insulin synthesis
proinsulin - big hormone a and B chain made as 1 chain joined by C(connecting)-peptide
C-peptide cleaved
a and B chain joined by disulphide bridges
C-peptide longer half life than insulin - measure to see if pancreas is working
describe the secretion of insulin
glucose enter Glut 2 g-6-p ATP block ATP sensitive K+ channel cause Ca2+ in through voltage dependant Ca channel insulin released from B cell
comparison of oral or Iv glucose
oral higher insulin release - incretin affect
describe glucagon like peptide 1 (GLP-1)
gut hormone - secreted in response to nutrients in gut
transcription product of proglucagon gene - mostly from L cell
stimulates insulin, suppresses glucagon
increase satiety (feeling full)
short half life - rapid degradation from dipeptidyl peptidase-4 (DPPG-4 inhibitor)
treatment of T2 - injection because big hormone
describe the islets of Langerhans
2% pancreas
a - glucagon
B - insulin
d - somatostatin
gap junctions - small molecules pass between cells
tight juctions form small intercellular spaces where hormones are held and have paracrine effects
relationship between insulin, somatostatin, glucagon
somatostatin inhibits insulin and glucagon
insulin stim growth and development - intermediary metabolism, decrease blood glucose
glucagon - increase blood glucose, liberate glucose from liver maintain 3.5mML
what stimulates insulin production
certain AA increase blood glucose B receptors - parasympathetic activity GLP1 - therapeutic target glucagon
what inhibits insulin production
a-receptors - parasympathetic activity
somatostatin
effect of insulin
increased AA transport and protein synthesis, lipogenesis
decreased lipolysis, gluconeogenesis, glycolysis, glucose into cell by Glut 4 - decreased blood glucose
what stimulates glucagon production
certain AA
sympathetic and parasympathetic activity
certain GI hormones
what inhibits glucagon production
insulin
somatostatin
effect of glucagon
increased: lipolysis, gluconeogenesis, AA to liver, gluconeogenesis, hepatic glycogenolysis, blood glucose, increase hepatic glucose output (HGO)
describe 1st phase insulin release
insulin is stored then make insulin to cope
diabetes - chronically stressed don’t have 1st release
Describe the insulin receptor
deterioration doesn’t cause t2DM
on muscle and liver
recognise 3D structure
transmembrane pass message onto cytoplasm
phosphorylation of cell protein substrates
tyrosine kinase domains
cause mitogenic growth effects
where is leptin produced
white fatty deposits
is glucosuria diagnostic of DM
no
Do increased plasma non-esterified fatty acid concentrations stimulate insulin secretion
no
