insulin 4
Endocrine Pancreas
Hormones of the Pancreas
Islets of Langerhans innervated
parasympathetic,
sympathetic and
peptidergic nerves
glucagon
insulin
somatostatin
(F) pancreatic polypeptide
CHO metab. mainly: but consider protein and fats because of the inter relationship
INSULIN
Structure:
Polypeptide
A & B chains: Linked by disulphide bonds
aa sequence different from sp. to sp.
Synthesis
Large pre-prohormone
Proinsulin
Insulin + connecting peptide
Insulin Structure
Metabolism
Almost all tissues (but mainly, Liver/kidney)
1/2Life 5-8 mins
Inactivated by breaking disulphide links
Insulinase (general term)
(hepatic glutathione insulin transhydrogenase)
Secretion & control
Metabolic effects of Insulin (3 categories)
Carbohydrate metab.
Stimulation of glucose uptake by cells
Stimulation of glycolysis
Stimulation of Glycogen synthesis
Inhibition of glycogen catabolism
Inhibition of Gluconeogenesis
Net effect
Decrease in plasma glucose concentration increase in glucose utilization
Net glucose uptake rather than release by the liver
Effects
Fat Metab.
Stimulation of tri-acyl glycerol synthesis
Inhibition of triacyl glycerol catabolism
Stimulation of endothelial cell lipoprotein lipase
Net effect:
Decrease in plasma conc. of glycerol and FFA
Net storage of fat decreased utilization of fat for energy
Effects
Protein metab.
Stimulation of amino acids uptake by cells
Stimulation of protein synthesis
Inhibition of protein degradation
Net effects:
decreased plasma conc. aa.
Net protein anabolism
Other effects
Cause the movement of K+ into cells ? stimulation of Na+K+ ATPase
Hypokalemia causes insulin secretion
Thiazide diuretics cause hypoKalemia
Thiazides are diabetogenic
Exercise
Increases the movement of Glucose into cells
Increases affinity of glucose receptors in muscle
Reduction of blood sugar
DIABETES MELLITUS
Lack of insulin or abnormal receptors
Effects:
Reversal of all physiological effects
CHO:
Increased blood glucose
Non utilization of glucose
Hyperglycemia
DM
Protein
decreased protein synthesis
conversion to glucosehyperglycemia
wasting
resistance to infection
sugar in blood--good culture medium for bacteria
DM
FAT metabolism
lipid catabolism
synthesis of fatty acids and triglycerides
glucose is not converted to fatty acids
Metabolism of free fatty acids to Acetyl-CoA
DM
Acetyl CoA is not converted to fatty acids
Acetyl CoA x2
Acetoacetate
acetone
-hydroxybutyrate (ketone bodies)
Acids H+ Low pH
EffectDeep rapid respiration (Kussmaul’s breathing)
DM
Blood sugar
Tm exceeded
osmotic diuresis
polyuria
glycosuria
polydipsia
Polyphagia
DM
H2O, Na+,K+ lost in the urine
Electrolyte imbalance
Dehydration
Hypovolemia
Hypotension
Acidosis, hyperglycemia, dehydrationCOMA
Hypokalemia (may be aggravated by insulin therapy)
DM
Hypercholesterolemia
Arteriosclerosis vascular disease
complications
Kidney
eyes peripheral nerves
DM (Causes of Coma)
acidosis
hyperosmolality
lactic acidosis
cerebral oedema
Types of DM
Type 1 Juvenile onset IDDM
lack of insulin
acidosis, ketosis
Type II Adult onset. NIDDM
Usually above 40
obese
Insulin levels normal
No ketosis
Reduced number of insulin receptors on adipose tissue
reduce weight receptor sites increased
DM
Hypothesis
Obesity and over eating
Stimulation of insulin receptor sites
Down regulation of receptors
insulin insensitivity
Pancreatic reserve exceeded
Failure to recognise glucose as a stimulus for the secretion of Insulin
Insulin Excess
Iatrogenic
Insulinoma (tumours of Islets)
Effects
Increase uptake of glucose
Hypoglycaemia
Main effects on CNS
Confusion
weakness
Dizziness
hunger
Hypo Effects
Stimulation of Sympathetic activity
effects,
Nervousness
excitability of cardiac muscle
sweating
Hypoglycaemic effects: rate at which blood sugar falls vis-a-vis compensatory mechanisms
DM Pathophysiology
Pathophysiology
Symptoms and signs
DM
Type II DM
GLUCAGON
Polypeptide
Action: gluconeogenic
lipolytic
Ketogenic
1/2 life 5-10 minutes
effects opposite to insulin and similar to lack of insulin
The End