Normal carbohydrate metabolism

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  • Normal plasma glucose concentration is between 4.5 and 11mmol/L
  • Almost all the glucose filtered by the renal glomeruli is reabsorbed by the renal tubular cells, glycosuria only occurs if the ‘renal threshold’ is reach which is about 11mmol/L

Insulin

 

  • Produced with a linking peptide, C-peptide
  • Enhan ces the rate of entry into adipose and muscle cells
  • Induces enzymes which stimulate glycogen synthesis (glycogenesis) and inhibits the production of glucose (gluconeogenesis) from fats and amino acids by inhibiting fata dn protein breakdown
  • Transport of glucose into liver cells is insulin independent but by reducing the intracellular glucose concentration it indirectly promotes the passice diffusion of gluscose into the cell
  • Insulin increases the transport of amino acids, potassium and phosphate into cells especially muscle. This is independent of glucose transport
  • Insulin is stimulated by various gut hormones incuding glucagons and gastric inhibitory peptide
  • It induces glucokinase in the liver
  • Promotes glycolysis by stimulating the expression of phosphofructokinase , pyruvate kinase and fructose-2,6-bisphosphate

Glucagon

 

  • Synthesised by alpha cells of the pancreatic islets
  • Secretion is stimulated by hypoglycaemia
  • Enhances hepatic gluconeogenesis and glycogenolysis
  • The following hormones are hyperglycaemia;
    • Growth hormone
    • Glucocorticoids
    • Adrenalin
    • Glucagons
  • Secretion of these hormones during periods of stress and in patients with acromegaly (GH), in Cushing’s syndrome (glucocorticoids) or phaeochromocytoma (adrenalin/noradrenalin) oppose the normal action of insulin

The liver

  • Portal venous blood from the intestine reaches the liver first, therefore the hepatic cells are important to buffer the effect of  high carbohydrate meal
  • Entry of glucose into liver cells (and brain cells) is not affected by insulin but depends upon extracellular glucose concentration
  • The conversion of glucose into glucose-6-phospate is catalysed in the liver by glucokinase which has a low affinity for glucose in comparison to hexokinase found in other tissues. Therefore proportionally less glucose is extracted by hepatic cells during fasting. This helps to maintain a fasting supply of glucose to vulnerable tissues such as the brain
  • Liver cells can store excess glucose as glycogen. The rate of glycogen production can be increased by insulin
  • Liver can covert some excess glucose to fatty acids which are transported as triglyceride in VLDL to be stored in adipose tissue
  • The liver can synthesis glucose by gluconeogenesis from the deamination of certain amino acids (mostly alanine)
  • The liver contains glucose-6-phosphatase which by hydrolysising G-6-P releases glucose
  • During fasting the liver converts fatty acids, released from adipose tissue to ketones which can be used as an energy source when the glucose concentration is low
  • The renal cortex is the only other tissue capable of gluconeogenesis. This is probably important in hydrogen ion homeostasis

Ketosis

  • In the liver triglycerides are formed from;
  • Glycerol-3-phosphate (from triose phosphate)
  • Fatty acids (from acetyl coA)
  • Triglycerides are transported to adipose tissue via VLDL and are hydrolysed by lipoprotein lipase to release fatty acids which are thenre-esterified within the cells with glycerol-3-phosphate derived from glucose. This produces a triglyceride which is stored
  • During fasting, endogenous triglycerides are reconverted to free fatty acids and glycerol by lipolysis, both are transported to the liver, the fatty acids being bound to albumin. Glycerol can enter the gluconeogenic pathway
  • Most tissues can oxidise fatty acids to acetyl CoA which can then be used to enter the Kreb’s cycle
  • Ketones are produced by the rate of synthesis of acetyl CoA exceeds its use and the hepatic cells produce acetoacetic acid by enzymatic condensation of two acetyl coA molecules. This can then be reduced to b-hydroxybutyric acid which can be reduced to acetone
  • Therefore ketosis occurs when fat stores are the predominant energy source

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