Glycemic Responses and Glycogenesis

• Glycation: non-enzymatic glycosylation of proteins
• Glucose reacts with proteins, forming covalent bonds and therefore destroying their functionality
• The rate of glucose destroying proteins is directly proportional to glucose concentration
• Glycation still occurs at 5mM
• HbA1c refers to the glycation of haemoglobin, which is an indicator of blood glucose concentrations over the last 3 months
• Tolerant glucose response

  • Basal level around 5mM
  • Roughly two hours required to return to basal level after eating
• Intolerant glucose response

  • Normal fasting glucose
  • More exposure to high BG between meals
• Diabetic glucose response

  • Hyperglycaemia while fasting
  • Relentless exposure to high BG
• Alpha cells secrete glucagon when [glucose] < 4.5mM
• Beta cells secrete insulin when [glucose] > 5mM
• Insulin stimulates the uptake and disposal of glucose
• Amino acids also stimulate insulin secretion
• Tolerant, insulin resistant

  • Normal BG homeostasis is achieved but this requires more insulin
• Intolerant

  • Secreting large amounts of insulin but this is not enough to overcome resistance
  • Constant hyperglycemia
• Type 2 diabetes

  • Beta cells are worn out from constantly secreting insulin
  • Beta cells can no longer secrete large amounts of insulin
• Starch is the main source of dietary carbohydrate
• Starch is a polymer of glucose
• What are the two main forms of starch?

  Amylose and amylopectin
• Why is amylose harder to digest than amylopectin?

  It is long and densely packed, meaning that it is harder for amylases to penetrate
• The glycemic index (GI) describes the post-prandial glucose response
• GI is given by the area under the test food curve divided by area under the reference curve
• The liver is the initial filter of glucose as blood comes in the hepatic portal vein
• How is 'activated glucose' formed in muscle for glycogenesis?

  After trapping and isomerisation, G1P is reacted with UTP leaving UDP bound to the glucose
• UDP glucose is added to the non-reducing end of glycogen to create a chain
• ATP is used during glycogen synthesis to:

  1. Activate glucose
  2. Convert UDP back into UTP
• Branching enzyme adds branches to the glycogen chain
• How does branching enzyme add branches?

  cleaves them from the long chain and then re-joining them parallel
• Glycogen synthase is regulated by reversible phosphorylation
• glycogen synthase is active when dephosphorylated
• Dephosphorylation of glycogen synthase is catalysed by protein phosphatase I
• Phosphorylation of glycogen synthase is catalysed by glycogen synthase kinase
• Insulin stimulates PPI
• Why does glycogenesis require glycolysis?

  Glycogenesis creates an energy charge demand, stimulating PFK
• The liver has glucokinase, which is a specialised form of hexokinase
• a rise in [G6P] caused by glucokinase activates glycogen synthase without the need for insulin
• In the liver, glycogenesis responds to blood glucose without the need of insulin (thanks to glucokinase), however insulin will stimulate glycogen synthase further
• In the muscle [G6P] never gets high enough to stimulate glycogen synthase, so insulin is required to stimulate glycogen synthase
• Glucokinase only works on glucose
• Glucokinase is not inhibited by G6P
• Glucokinase is only present in the liver