Insulin secretion and intermediary metabolism and diabetes Mellitus Flashcards
What 4 factors increase blood Glucose levels?
Glucagon Catecholamines Somatotrophin Cortisol
What do delta cells produce?
somatostatin
What proportion of the pancreas is associated with exocrine and endocrine function?
98% exocrine 2% endocrine
Briefly describe how insulin produced
- Synthesised from prohormone 2. Signal sequence cleaved off 3. 3 Disulfide bridges formed 4. C chain is cleaved off
Where is GLUT 4 mainly found?
muscle and adipose tissue
Draw a diagram to show how insulin is produced from beta cells
What’s the role of somatostatin?
reduces secretion of insulin and glucagon
What does insulin reduce?
- glycogenolysis in muscle + liver
- gluconeogenesis in liver
- breakdown of amino acids in liver
- lipolysis
- production of ketone bodies from NEFA
What does insulin increase?
- glycogenesis in muscle + liver
- glycolysis in liver + adipose tissue
- Amino acid uptake + protein synthesis in muscle, liver + adipose tissue
- Lipogenesis and esterification of FA in liver + adipose tissue
- Glucose uptake via GLUT 4, causes 7 fold increase in muscle + adipose tissue
What happens during the fasted state?
What happens during the fed state?
What happens during increased blood glucose?
What happens during decreased blood glucose?
How do sulphonylureas work?
Close ATP sensitive K + channel hence initiate insulin secretion
How is insulin secretion regulated?
What is the incretin effect?
- Different insulin response to oral vs IV glucose
- GLP-1 is a gut hormone
- Secreted in response to nutrients in the gut
- Transcription product of proglucagon gene, mostly from L cell
- Stimulates insulin, suppress glucagon
- Increases satiety
- Short half life due to rapid degradation from enzyme dipeptidyl peptidase-4 (DPPG-4)
What are the three main ketone bodies?
Acetone
Acetoacetate
3-hydroxybutyrate
What is T1DM?
ABSOLUTE insulin deficiency
What causes T1DM?
Autoimmune destruction of pancreatic beta cells
What does GLP-1 stand for?
Glucagon like peptide -1
What are the symptoms of T1DM ?
- Proteolysis with weight loss
- Hyperglycaemia
- osmotic symptoms
- Ketonuria
- Polyuria
- Polydipsia
- Glycosuria
What is hypoglycaemia?
plasma glucose <3.6 mmol/l, consciousness is impaired at <2 mmol/l
Where does insulin resistance lie?
liver, muscle and adipose tissue
What does omental fat/waist circumference indicate?
an individual’s risk of ischaemic heart disease
Define ketone bodies
3 water-soluble molecules that are produced by the liver from fatty acids during periods of low food intake or carbohydrate restriction.
What are the symptoms of T2DM?
- 60-80% obese
- Dyslipidaemia
- Later insulin deficiency ( exhaustion of beta cells )
- hyperglycaemia
- fewer osmotic symptoms
- T2DM presents often with complications
What two pathways does insulin have an effect on?
Metabolic Pathway (PI3K-Akt) Mitogenic Pathway (MAPK) - increased affect on this pathway
compensatory hyperinsulinaemia
How can you differentiate between T1DM and T2DM?
REMEMBER: insulin inhibits the conversion of fatty acids to ketone bodies
HIGH glucose + HIGH ketone bodies = T1DM
Usually, people with T2DM still produce enough insulin to suppress ketone body production though their blood glucose will be high.
What diet changes are recommended to someone with T2DM?
Reduce:
- fat
- refined carbohydrates
- sodium
Increase:
- complex carbohydrates
- soluble fibres
Why is First Phase Insulin Release (FPIR) important?
Switches off hepatic gluconeogenesis
