The Pancreas and Insulin

The normal blood glucose in the body is 4-6mM and is controlled by pancreatic hormones insulin and glucagon.

It is important to control these as certain organs like the brain can only use glucose as a respiratory substrate.

– Normally glucose –> broken down by glycolysis –> enters Krebs cycle –> oxidative phosphorylation.

– Cells can also metabolize fat –> produces reduced FAD/NAD which enter oxidative phosphorylation.

 

But some organs like the brain cannot break down fat and instead use ketone bodies which are made in the liver.

– Acetyl CoA + Acetyl CoA –> Acetoacetyl CoA –> HMG-CoA –> Acetyl CoA + Acetoacetyl CoA

 

These ketone bodies are an alternative fuel source – They are Acetone, Acetoacetate and B-hydroxybutyrate.

 

– This is a peptide hormone which is synthesized in the b-cells in the islets of Langerhans in the pancreas.

– When blood glucose increases, more glucose enters the cells through GLUT2 channels –> more glycolysis occurs –> increase in cell ATP

– ATP binds to KATP channels (which is attached to sulphonylurea receptor) closing them –> leads to cell depolarisation

– Voltage gated Ca2+ channels open –> increase in exocytosis of insulin.

There are many factors which affect insulin release in the body:

i) Cephalic phase – parasympathetic stimulation (using Ach) of Beta-cells promotes anticipatory insulin release before consuming a meal

ii) Blood glucose – insulin levels rise if [glucose] > 5mM

iii) Incretins – GIP and GLP-1 are stomach hormones released in response to oral glucose. These stimulate insulin release and inhibit glucagon.

– These are broken down by enzyme dipeptidyl peptidase 4 (DPP-4)

iv) Sympathetic stimulation – it inhibits insulin release, allowing blood glucose to increase in exercise.

 

Insulin actions:

Insulin exerts its effect by binding to the insulin receptor – a tyrosine kinase linked receptor.

– Acts through messenger Akt2 which aims to reduce blood glucose and increase storage as glycogen and fat.

Muscle:

– Promotes glucose uptake by translocation of GLUT4 to membrane + glucose metabolism and glycogenesis

– Stimulates amino acid uptake and protein synthesis

 

Fat:

– Promotes glucose uptake and conversion to fat

– Inhibits fat breakdown and promotes fat uptake

Liver:

– Promotes glycogenesis and fat synthesis

– Inhibits gluconeogenesis and glycogen breakdown.

 

–> Glucagon:

On the other hand, glucagon is produced by the a-cells in the islets of Langerhans. It works to ­ blood glucose and fatty acids, acting as the main catabolic hormone of the body

 

Release:  Produced by the pancreas when concentration of insulin and glucose in the bloodstream falls too low. – Stimulated by hypoglycaemia and adrenaline but inhibited by insulin and hyperglycaemia

 

Actions: Promotes gluconeogenesis + glycogenolysis in the liver raising free blood glucose

– Decreases fatty acid synthesis + promotes lipolysis in liver and adipose for use by skeletal muscle.

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