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diabete mellitus

• colection of diseases of glucose homeostasis

1. type 1 diabetes
2. types 2 diabetes
3. MODY
4. gestational diabetes
5. T2DMY

• accounts for 10% of NHS budget
• associated with serous complications
• shortens lifespan/accelerates ageing

classification

Type 1 diabtetes

• immune mediated 
• idiopathis
• formerly insulin-dependent diabtetes

Type 2 diabtetes

• insulin resistance with inadequate insulin secretion
• formely non-insulin dependent diabtetes

seondary diabetes

• diabetes secondary to pancreatic diabetes

1. chronic pancreatitis
2. haemochromatosis
3. pancreatic surgery or trauma
4. cystic fibrosis

• diabetes secondary to drugs and chemicals

1. glucocorticoids
2. diuretics
3. antipsychotics
4. B-blockers

• diabetes secondary to genetic abnormalities

1. genetic deffects of B-cell function
2. gentic disorders of insulin action

• infections

1. congenital rubella
2. cytomegalovirus
3. mumps

• gestational diabetes

normal glucose homeostasis

Post- prandialy

• glucose comes from GI tract via SGLT1
• glucose stimulates insulin release from pancreatic-beta cells
• insulin promotes glucose uptake in hepatocytes, skeletal muscle and adipocytes

fasting state

• glucose drops- lowering insulin
• catabolism occurs

insulin secretion

insulin is produced by pancreatic beta-cells

• 51aa peptide comprising 2 chains
• synthesised on RER as pre-proinsulin 
• signal peptide remoed before transfer to golgi
• cleaved by PC1/3 to form mature insulin
• stored in secretory granules

insulin release

• nutrient response - biphasic pattern
• basal secretion does occur
• catabolism occurs

sequence of reactions

1. amino acids, transfer -RNA, ATP,GTP,Mg2+, etc
2. pre-proinsulin synthesis
3. proinsulin transfer
4. packaging in vesicles containing membrane-bound proteases
5. +zn2+ and release of Arg, Lys
6. conversion of pro-insulin to insulin
7. crstalloid zinc-insulin core surrounded by C-peptide
8. Ca2+ and energy-dependent secretion of insulin and C-peptide

increased by:

• nutrients - raised glucose, amino acids
• hormones- glucagon, gastrin, secretin, cholecystokinin, GIP, GLP-1
• pancreatic innervation -signalling via sympathetic, parasympathetic

• insulin -> phosphorylation of…