Pancreas + diabetes
Pancreas
- Retroperitoneal (apart from tail)
- 12-15cm long
- Lateral to medial: tail - body- neck- head - unicinate process
- Head and uncinate process enclosed in 3/4 duodenum
Function
Endocrine
Hormones straight into bloodstream from islets of Langerhands: cluster of cells
Exocrine
- GI tract: secreting digestive enzymes
- Insulin + glucagon
- Regulate blood glucose
- Somatostatin + pancreatic polypeptide
- Alpha cell: Glucagon
- Beta cell: Insulin
- Delta cell: Somatostatin inhibits insulin and glucagon
- F cells: inhibits somatostatin
Insulin
- Beta cells
- 2mg secreted per day
- 6-10 mg in pancreas
- High blood glucose:
- Stimulated PSNS
- Intestine secretes incretins (gastric inhibitory polypeptide (GIP) and glucagon like polypeptide -1 (GLP-1) when glucose ingested - stimulates release of insulin
- Increase uptake + storage of glucose (lowers blood glucose levels)
- Glucose stored as glycogen
- Insulin targets glucose uptake in liver, muscle and adipose tissue
Glucagon
- Alpha cells
- Secreted response low blood glucose level (fasting)
- Targets mainly liver, stimulate breakdown glycogen to glucose
- Inhibits glycogen/fatty acid synthesis (diminishing production of pyruvate)
- Gluconeogenesis in liver
- Inhibits glycolysis
- Glucagon release glucose from liver cells, increase blood glucose levels
Transporters
Facilitated glucose transporters (GLUT)
- Glucose transported into cells via facilitated diffusion
Sodium dependent glucose transporters
- Glucose uptake from intestinal lumen into villi of lining
GLUT
GLUT 3
GLUT 4
GLUT 2
GLUT 5
GLUT 1
Brain, erythrocytes, placenta and fetal tissue
High affinity binding for glucose + uptake from blood stream constant
Liver , kidney, intestine, pancreatic beta cell
Lower but high. Intracellular + extracellular equillibrate across membrane
Glucose entry proportional to blood glucose levels
Brain
Higher affinity GLUT 2
Preferential uptake hypoglycemia
Muscle + adipose tissue
: Signalling cascade culminate movement cytoplasmic vesicles towards cell surface membrane
INSULIN SENSITIVE uptake glucose after food intake
Medium affinity.
Recruits transporters from intracellular stores, increasing glucose uptake
Jejunum
Medium affinity
Fructose intake
- Higher affinity transporters: brain
- Liver not insulin dependent glucose uptake . Insulin accelerates uptake via GLUT 2 in liver
Insulin in muscle and adipose tissue
- Insulin binds receptor kinase cell membrane: phosphorylates insulin receptor substrate (IRS-1)
- Protein kinase cascade
- More GLUT 4 integrated plasma membrane
- Increased glucose uptake via GLUT 4 into cell
- Glycogen synthesized from glucose and stored in cells
Insulin in liver
- GLUT 2 not dependent insulin, accelerates glucose uptake liver
- Glucokinase sites occupied by glucsoe, phosphorylated into G6P
- Increase in G6P build up glycogen stores
- glycogen released as glucose
Adrenal glands glucose reg
Prolonged fasting form of stress: stress results in cortisol release
- Breakdown glycogen
- Conversion amino acids, lactate, glycerol to glucose in liver
- Promotes breakdown of body portein - amino acid- glucose in liver
During fasting, small amount adrenaline secreted into circulation
- Promotes breakdown glycogen to glucose in skeletal muscle
- Not released in to blood, additional energy source muscle cells
- Little lactate may be produced - glucose into liver- into bloodstream
Diabetes
Type 2
Type 1
- Autoimmune destruction beta cells
- Little/no insulin produced
- In childhood/before 40
- Insulin treatment
- Thirst, polyuria and weight loss
- Body uses lipids and proteins to make glucose
- Uncontrolled catabolism: Ketoacidosis
- Peripheral lipolysis: circulating free fatty acicds
- Converted into acidic ketones in liver: metabolic acidosis
- Peripheral tissues not as responsive to insulin, more insulin produced beta cells compensate (hyperinsulinaemia)
- Function of beta cells decline, cannot compensate for insulin resistance hyperglycaemia - diabetes
- Usually over 40
- Obesity major risk factor