biochemistry Flashcards
what glucose level is hypoglycemia
<4mM
what blood sugar level is considered high (risk of diabetes)
6-7mM
what blood sugar is considered very high (diabetes)
> 7mM
what do beta cells secrete
insulin
what do alpha cells secrete
glucagon
what do gamma cells secrete
somatostatin
what do PP cells secrete
pancreatic polypeptide
where is preporoinsulin synthesised
in the RER of pancreatic beta bells
what happens after preproinsulin
cleaved to form proinsulin and a signal peptide which is then cleaved to form C peptide and insulin
three chains of proinsulin
C peptide
A chain
B chain
what is pure insulin then made up of
A chain and B chain
5 types of synthetic insulin preparations
- ultra fast/ultra short acting
- short acting
- intermediate acting
- long acting
- ultra long acting
what is the name of the ultra fast insulin
lispro
when is lispro used
15 minutes of beginning a meal
-must be used in combination with long acting ones
what is the most commonly used long-acting insulin
glargine
when is glargine used
single bedtime dose
what does glucose enter the beta cells through
the GLUT2 glucose transporter
what is glucose phosphorylated by
glucokinase
at what mmol/L of glucose does glucokinase start being more active
7
what does an increased metabolism of glucose lead to in terms of ATP
leads to an increase in intracellular ATP concentration
how many ATP is produced per glucose
36
what does ATP then inhibit (in the secretion of insulin)
the ATP-sensitive K+ channel Katp
what does inhibition of Katp lead to
depolarisation of the cell membrane
what does depolarisation fo the cell membrane lead to in insulin secretion
opening of voltage-gated Ca2+ channels
what does an increase in calcium concentration lead to
fusion of secretory vesicles with the cell membrane in release of insulin
what happens in T1DM to the beta cells
they are mostly lost
what does the first phase of insulin secretion prevent
a sharp increase in blood glucose
what does the second phase of insulin secretion look like
broader and shorter
why are there two phases
- 5% are immediately ready for release (RRP)
- reserve pool must undergo preparatory reactions to be ready to be released
why in poorly controlled T2DM does insulin secretion weaken and flatten
- downregulation of the sensing process
- limited glucokinase activity
- mitochondrial exhaustion
- reduced ATP production
what is wrong in type 1 diabetes
destruction of pancreatic beta cells
what is wrong in type 2 diabetes
hyperinsulinemia as the beta cells try to compensate for the hyperglycemia caused by insulin resistance
later stages of type 2 diabetes, what can go wrong?
-decline in beta cell function
what is associated with gestational diabetes
women with declining beta cell formation and high risk of future T2DM
develops during pregnancy
what is maturity onset diabetes of the young (MODY)?
monogenic disease with common clinical features to both type 1 and 2
-beta cell dysfunction but not autoimmune destruction
what is neonatal diabetes
rare form of monogenic diabetes which is mainly caused by mutations in the glucose sensing mechanism
what are the two proteins in the Katp channel
Kir6
SUR1
what can mutations in Kir6.2 lead to
neonatal diabetes
-as unable to secrete insulin
what mutations can cause congenital hyperinsulinism
Kir6.2 and SUR1
where do the mutations in MODY mostly happen
in glucokinase
-also several transcription factors (5)
in which transcription factors are most of the MODY mutations
HNF 1 and 3
what defines type 1 diabetes
loss of insulin secreting beta cells
what defines MODY
defective glucose sensing in the pancreas and/or loss of insulin secretion
what defines type 2 diabetes
initially hyperglycemia with hyperinsulinemia so primary problem is reduced insulin sensitivity in tissues
what does insulin regulate
- amino acid uptake in muscle
- DNA synthesis
- protein synthesis
- growth responses
- glucose uptake in muscle and adipose tissue
- lipogenesis in adipose tissue and liver
- glycogen synthesis in liver and muscle
- gene expression
- turns off lipolysis and gluconeogenesis in liver
how can obesity cause insulin resistance
due to excess fat deposition in liver, muscle and pancreas, reducing insulin signalling in those tissues, combined with a deficit in adipose functionality
symptoms of diabetic ketoacidosis
- vomiting
- dehydration
- increased heart rate
- distinctive smell on breath
where are ketone bodies formed
liver mitochondria
how does insulin usually reduce the risk of ketone body overload
by inhibiting lipolysis
when is DKA a risk in T1DM
if insulin supplementation is missed and hyerglycemia ensues
what results in fatty acid oxidation in relation to insulin
having no insulin reduces the amount of glucose being taken up by tissues from blood and reduces glycolysis making the body switch to fatty acid oxidation
what causes ketones to be produced as a result of fat utilisation
- fat utilisation outstrips glucose utilisation
- no glycolysis
- pyruvate/oxaloacetate is limited
- acetly CoA is diverted to ketones
what can cause ketosis
- starvation
- diabetes
