Blood glucose Flashcards

1
Q

What is glycaemia?

A

blood glucose levels

- needs to be regulated

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2
Q

How is glucose obtained?

A

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
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3
Q

What are the different mechanisms for glucose entry into the blood?

A

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
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4
Q

How can glucose be used?

A

metabolised for energy
converted to glycogen for storage
stored as triglycerides
used for cell growth processes

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5
Q

What are normal glycaemia levels? What is abnormal/suspected diabetic range? What is the target level for diabetics?

A

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)
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6
Q

What are the mechanism to increase blood sugar levels during low blood glucose levels?

A

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

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7
Q

What are the mechanism to decrease blood sugar levels during high blood glucose levels?

A

peripheral glucose uptake
- uptake of glucose by cells

glycogenesis
- glycogen synthesis from glucose = stored as glycogen mainly in the liver and muscle

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8
Q

What are the islets of langerhans? What are the different cells in the islets of langerhans? What are their functions?

A

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

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9
Q

What is the function of somatostatin? Where is it secreted from?

A

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)

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10
Q

What is the function of amylin? Where is it secreted from?

A

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)

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11
Q

What is the structure of insulin?

A

2 polypeptide chains: A and B

  • have two disulphide bridges connecting them
  • has an internal disulphide bridge in chain A connecting to itself
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12
Q

What stimulates insulin release?

A

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

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13
Q

How is insulin formed?

A

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

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14
Q

What are the different mechanisms insulin uses to regulate glucose homeostasis?

A

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
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15
Q

How is insulin release from its vesicles stimulated?

A

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

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16
Q

How does insulin stimulate glucose uptake into cells?

A

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

17
Q

How glucagon stimulate increase in blood glucose concentration?

A

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

18
Q

What stimulates glucagon release?

A

channels in the pancreatic alpha cell generate action potentials of sodium and calcium at the low levels of glucose
- leads to glucagon release

19
Q

What is the role of the liver in glucose homeostasis?

A

liver is the primary organ for glucose metabolism

maintains a balance between

  • the uptake and storage of glucose
  • glycogenolysis and gluconeogenesis
20
Q

How does the liver take up glucose?

A

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.
21
Q

When are glycogenolysis and gluconeogenesis important? When do they occur? What enzymes are involved in glycogenolysis and gluconeogenesis?

A

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

22
Q

What is diabetes? What is the difference between type 1 and type 2 diabetes?

A

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
23
Q

What occurs during emergency glucose resuscitation?

A

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