Blood glucose Flashcards
What is glycaemia?
blood glucose levels
- needs to be regulated
How is glucose obtained?
from the diet
- monosaccharides = glucose, fructose, galactose
- disaccharides = maltose, sucrose, lactose are digested by pancreatic amylase
- polysaccharides = digested by salivary amylase in dextrin which are digested by pancreatic amylase
What are the different mechanisms for glucose entry into the blood?
monosaccharides are absorbed in the small intestine
- only as monosaccharides so carbohydrates must be digested
sodium glucose linked transporter (SGUL)
- cotransporter/symporter = sodium and glucose together
- secondary active transport = rely on concentration gradient generated by the Na-K+ ATPase pump (3Na+ out, 2K+ in)
glucose diffusion facilitated transporter (GLUT-)
- facilitated diffusion
- uniporter = glucose only
- along the concentration gradient
- are hydrophilic so need a transporter
sugar efflux transporter
- uniporter
- maintain glycaemia
- mediate glucose efflux from the liver
How can glucose be used?
metabolised for energy
converted to glycogen for storage
stored as triglycerides
used for cell growth processes
What are normal glycaemia levels? What is abnormal/suspected diabetic range? What is the target level for diabetics?
normal operating range
- fasting = 4-5.4 mmol/L
- 2 hours after eating = less than 7.8 mmol/L
suspected diabetic
- fasting = 5.5-6.9 mmol/L (too high)
- 2 hours after eating = 7.8-11 mmol/L (too high)
target levels in diabetics
- fasting = 4-7 mmol/L (too high)
- 2 hours after eating = 8.5-10 mmol/L (too high)
What are the mechanism to increase blood sugar levels during low blood glucose levels?
glycogenolysis
- breakdown of glycogen stored in muscle and liver into glucose
gluconeogenesis in the liver
- synthesis of glucose from non-carbohydrate precursors
= lactate, pyruvate, glycerol
What are the mechanism to decrease blood sugar levels during high blood glucose levels?
peripheral glucose uptake
- uptake of glucose by cells
glycogenesis
- glycogen synthesis from glucose = stored as glycogen mainly in the liver and muscle
What are the islets of langerhans? What are the different cells in the islets of langerhans? What are their functions?
islets of langerhans are pancreatic cells which secrete hormones
exocrine pancreas
- made up of acincar and duct cells
alpha cell
- secretes glucagon (hormone)
beta cell
- secretes insulin and amylin
delta cell
- secretes somatostatin
F cells
- secretes pancreatic polypeptide
What is the function of somatostatin? Where is it secreted from?
secreted by delta cells in the pancreas
- inhibits glucagon and insulin secretion
can also be secreted by other cells
- GIT = reduces gastric secretion, reduces/inhibits GI hormones (secretin, cholecystokinin)
What is the function of amylin? Where is it secreted from?
secreted by beta cells in the islets of langerhans along with insulin
- co-secretion in a ratio of 1:10 (a : i)
stored in the secretory granules of the beta cells
levels of amylin are directly proportional to the amount of body fat
inhibits glucagon secretion
reduces/delays gastric emptying
functions as an adiposity signal and satiety agent (feeling of being full)
What is the structure of insulin?
2 polypeptide chains: A and B
- have two disulphide bridges connecting them
- has an internal disulphide bridge in chain A connecting to itself
What stimulates insulin release?
is secreted if the blood glucose concentration is ≥ 3 mmol/L
- at ≥ 3 mmol/L, insulin is secreted from inside the vesicle with free C peptide
- at ≥ 5 mmol/L insulin is secreted from the beta vesicles
parasympathetic nervous system and gut hormones (secretin) can also stimulate insulin secretion
How is insulin formed?
initial precursor is preproinsulin
- has chain A, B and C and signal sequence at the N-terminus
preproinsulin is cleaved upon entry into the endoplasmic reticulum and forms proinsulin
- cleavage of the start signal sequence at N-terminus
proinsulin is folded within the ER and sent to the golgi
- chain C is cleaved off
- forms mature insulin with 2 polypeptide chains and a free C peptide form
free C peptide and insulin are packaged in the golgi into secretory granules/vesicles and accumulate in the cytoplasm
- released when needed
What are the different mechanisms insulin uses to regulate glucose homeostasis?
increasing the rate of glucose uptake, primarily into striated muscle and adipocytes
- with synthesis of glycogen and TG by adipose, muscle and liver cells)
- peripheral glucose uptake into cells
inducing a process of glycogenesis
- in the liver and muscle = glycogen synthesis from glucose = stored as glycogen
inhibiting gluconeogenesis and glycogenolysis
- gluconeogenesis = synthesis of glucose from non-carbohydrate precursors
- glycogenolysis = breakdown of glycogen stored in muscle and liver into glucose
How is insulin release from its vesicles stimulated?
glucose enters the cell
- facilitated diffusion by GLUT-2
glucose is phosphorylated into glucose-6-phosphate
oxidation of glucose-6-phosphate generates ATP
ATP acts on the ATPase Na-K+ channels
- inhibits K+ leaving by closing the channel
Increased K+/reduced exit depolarises the membrane
Depolarisation opens the voltage gated calcium channels
calcium enters the cell
calcium entry triggers the exocytosis of the insulin vesicles
insulin is released
How does insulin stimulate glucose uptake into cells?
insulin binds to the receptor tyrosine kinase (RKT)
RKT is activated
- cytoplasmic tails dimerise, autophosphorylation, kinase is activated
activation generates a binding site for signalling molecules
- insulin receptor substrate (IRS-1) binds and is activated by phosphorylation
- IRS-1 activates phosphoinositidine-3-kinase (PKB)
- PKB catalysis conversion of PIP2 to PIP3
- PIP3 induces activation of PI dependent kinase (PDK 1)
- PDK 1 activates other kinases
PKB translocates GLUT-4 (facilitated diffusion transporters of glucose) into the membrane
- allows diffusion of glucose into the cells
glucose uptake increases
How glucagon stimulate increase in blood glucose concentration?
glucagon is a hormone
- secreted by the alpha cells of islets of langerhans in the pancreas
- acts as the counter-regulatory hormone to insulin. insulin is stimulated at the same time and inhibits it when glucose levels are high enough
mechanisms
- promotes hepatic gluconeogenesis (liver)
- promoted hepatic glycogenolysis (liver)
- decreases glycogenesis and glycolysis
- reduces glucose uptake in insulin sensitive tissues (skeletal muscle and adipose tissue)
= promotes mobilization of stored precursors (AA and FFA) that can be used for gluconeogenesis
What stimulates glucagon release?
channels in the pancreatic alpha cell generate action potentials of sodium and calcium at the low levels of glucose
- leads to glucagon release
What is the role of the liver in glucose homeostasis?
liver is the primary organ for glucose metabolism
maintains a balance between
- the uptake and storage of glucose
- glycogenolysis and gluconeogenesis
How does the liver take up glucose?
hepatocytes take up glucose by GLUT-2 (facilitated diffusion transporters) in the presence of high concentrations of glucose and undergo:
- glycogenesis
- the pentose phosphate pathway
- glycolysis.
When are glycogenolysis and gluconeogenesis important? When do they occur? What enzymes are involved in glycogenolysis and gluconeogenesis?
glycogenolysis
- occurs within 2-6 hours after a meal
gluconeogenesis
- important for long periods of fasting
- controlled by activation of gluconeogenic enzymes
= cytokines, glucagon, steroid
- insulin can suppress the expression of gluconeogenic enzymes
What is diabetes? What is the difference between type 1 and type 2 diabetes?
diabetes
- chronic metabolic condition characterised by high blood sugar levels over a long period of time
type 1
- insufficient or absence of insulin production
- commonly affects children and young adults
type 2
- deficient insulin production or insulin resistance
- develops gradually with age
What occurs during emergency glucose resuscitation?
low blood glucose levels
- adrenaline stimulates glucose release from the liver
- glucose is directed towards the most essential organs via the arteries
= brain and CNS, muscle cells, immune cells
