absorptive state Flashcards
how is insulin release triggered in the pancreas?
- In the fed state blood glucose increases and it enters the pancreatic cells B cells in the islets of Langerhans via the GLUT2 TRANSPORTER when passing through. This causes an increase in K+, which then causes K+ channels to close, leading to depolarisation. This depolarisation causes Ca2+ channels to open, the influx of Ca2+ causes exocytosis of insulin
what is the difference between GLUT2 and GLUT4?
GLUT 2 is insulin independent
GLUT4 is insulin dependant
what does insulin activate in the hepatocyte?
stimulates glycogen synthesis and lipogenesis,
* glycolysis, VLDL apoproteins synthesis and protein synthesis
what does insulin inhibit in the hepatocyte?
glycogenolysis (glycogen phosphorylase) ,
* gluconeogenesis (phosphoenolpyruvate)
* Protein breakdown
what does insulin promote in muscle cells?
- GLUT4 recruitment (mainly occurs in adipose and myocyte cells)
- Glycogen synthesis and lipogenesis
- Glycolysis and protein synthesis
what does insulin inhibit in the the muscle cells?
- Limited gluconeogenesis possible, what is possible is inhibited
- Inhibits protein breakdown (as not needed as energy source)
what does insulin promote in adipocytes?
- Promotes GLUT4 recruitment
- Glycolysis and lipogenesis
- Chylomicrons and VLDL
what does insulin inhibit in adipocytes?
- Hormone sensitive lipase responsible for fat breakdown (breaks glycerol and fatty acid bond)
what is a glucose supplying reaction?
one that makes glucose
where can pyruvate be generated from for gluconeogenesis?
- AA’s broken down from proteins in muscles, aa deaminated etc in the liver to form pyruvate
- Fats from adipose tissue can also be broken down, the glycerol enter the blood stream and can be converted to glucose
what are the glucose supplying reactions?
gluconeogenesis
glycogenolysis
why are glucose sparing reactions needed in the post absorptive state?
glucose blood conc needs to be maintained for the brain to function
what promotes glucose supplying reactions?
- Glucose supplying reactions are promoted by glucagon secreted by A cells in the islets of Langerhans e.g. triggers glycogen breakdown
- Adrenaline activates a G protein leading to increase cAMP levels, this activates PKA which then activates glycogen phosphorylase
- Cortisol increases gluconeogenesis decrease glucose uptake
what are glucose sparing reactions?
alternative substrates to glucose are used in the post absorptive state
how are lipids metabolised in the post absorptive state?
lipids are cleaved by hormone sensitive lipase and the FA are then broken down by B oxidation to produce acetyl COA molecules
what activates / inhibits HSL?
HSL inhibited by insulins activated / promoted by glucagon
what activates glucose sparing reactions?
Adrenaline also stimulates Glucose sparing reactions it activates hormone sensitive lipase
explain type 1 diabetes
- Young age
- Loss / destruction of B cells in islets of Langerhans
- Leads to difficulty utilising glucose
- Energy from other reactions e.g. keto acids produced from fat (mainly) and also proteins can lead to ketoacidosis
- Weight loss
- Main treatment insulin injections
explain type 2 diabetes
- Prevalence increases with age
- Insulin resistance
- Also weight loss and keto acidosis
- Main treatment lifestyle changes some medicine may be used e.g. long acting insulin or Metformin and glucose monitoring
what are the effects of insufficient insulin on muscles?
gluconeogenesis and protein breakdown are not inhibited leading to muscle wasting a further increase in blood glucose levels
what are the effects of insufficient insulin on hepatocytes?
no binding of insulin to the receptor means that the processes such as glycogen synthesis are not promoted and furthermore glycogenolysis is not inhibited it continues leading to blood glucose levels rising even higher
what are the effects of insufficient insulin on adipose tissue?
HSL not inhibited, fatty acid breakdown not inhibited, excess beta oxidation leading to excess CoA and Keto acids = ketoacidosis
what consequence does glucose have for the bodies proteins?
- Elevated glucose reacts with proteins in the body the protein becomes more glycosylated into an AGE (advanced glycation end product) this changes the function leading to diabetic complications
- This process occurs often spontaneously without the control of enzymes
list the symptoms of diabetes cuased by AGE’s?
- Retinopathy - growth of poor quality new blood vessels in the retina due to protein damage. This leads to macular oedema (swelling of the macular key part of the retina for clear vision), damage vision to the point of blindness
- Neuropathy - decreased sensation in hands and feet (don’t feel damage), insufficient / damaged blood vessels growing to repair blisters, secondary bacterial infection could occur leading to infected / dead areas that may need to be amputated
- This is a result of delayed healing and secondary infections e.g. gangrene
