4- Insulin secretion and intermediate metabolism Flashcards
Name 4 common diabetes complications
Diabetic retinopathy
• Nephropathy
• Heart attacks
• Stroke
Why is glucose important
Glucose is a very important energy substrate, particularly for the CNS which mainly respires glucose under normal conditions.
• If blood glucose falls below 4.0-5.5mM (hypoglycaemia) - then brain function is increasingly impaired.
• If blood glucose falls below 2mM it could lead to unconsciousness, coma and death.
Describe islets of langerhan cells
Cells in the pancreas have Gap Junctions which allow the hormones to have an effect on adjacent cells - PARACRINE EFFECT
• There are also small collections of fluid between cells formed by Tight Junctions
• Alpha = Glucagon
• Beta = Insulin
• Delta = Somatostatin
• Somatostatin DECREASES the production of insulin and glucagon
What increases blood glucose
Glucagon Catecholamines Somatotrophin Cortisol
Describe neurological control of beta cells
Sympathetic Stimulation - switches off insulin to increase blood glucose concentration
Parasympathetic Stimulation - increases insulin secretion
What are some other effects of insulin
Insulin also prevents the break down of protein
• Insulin stops lipolysis and increases lipogenesis
• Without glucose, some amino acids can regulate insulin secretion
• Some gastrointestinal hormones increase insulin secretion - this is important
physiologically because before the food we eat even affects blood glucose, the
food in our gut is making us produce insulin
• In particular, Glucagon Like Peptide makes us produce insulin
Describe the effects of glucagon
Main effects are on the LIVER - increase hepatic glucose output
Decrease Blood glucose
Increased amino acid transport into liver
Increased lipolysis
How is blood glucose level detected
Glucokinase is the Rate Determining Step that regulates insulin secretion
• Glucose enters the cell via Glucose Transporter 2 (Glut 2)
• Glut 2 is NOT INSULIN REGULATED
• Glucose is converted to Glucose-6-phosphate by glucokinase which is
important for the sensing of glucose concentration by the beta cell
What is the structure of insulin
Insulin is constructed as pre-proinsulin which has three chains forming one long chain along with a signal sequence
• The C peptide is then removed (the middle chain), disulphide bonds formed
• Insulin being released by the pancreas is always released with C peptide
• The molar ratio of insulin to C peptide is 1:1 so by measuring C peptide you can
measure endogenous insulin production and see if the beta cells are functioning
How is insulin produced by beta cells
Glucose enters through Glut 2
• The ATP produced blocks the ATP sensitive potassium channels
• This leads to the opening of voltage dependent calcium channels
• Calcium rushes into the beta cell and insulin is secreted
What is the incretin effect
food stimulates more insulin secretion if given orally rather than intravenously
Describe glucagon like peptide-1
Gut hormone
• Secreted in response to nutrients in the gut
• It is a transcription product of the proglucagon gene - mostly from the L cell
• Stimulates insulin and suppresses glucagon
• Increases satiety (increases feeling of fullness)
• They have a short half life due to rapid degradation by the enzyme Dipeptidyl
Peptidase-4 (DPPG-4)
• DPPG-4 inhibitors can be used to treat T2DM
Describe the insulin receptor
Insulin is a protein/polypeptide hormone which does not cross membranes
• The alpha subunit of the insulin receptor recognises the 3D shape of insulin
which causes a conformational change in the beta subunits which cross the
membrane - this has a metabolic effect on glucose, amino acids and fatty acids
• It also affect growth (mitogenic pathway)
• Phosphorylation of beta subunits is important in recruiting substrates which go
on to have effects on the metabolic pathway
• Insulin resistance is NOT caused by the receptor not being able to recognise
insulin or due to the transmembrane portion of the receptor not working
• Insulin resistance lies in the post receptor cytoplasmic elements of insulin function
