Download Carbohydrate Metabolism 3

Dr. Hani Alrefai 04/11/2014
Dr. Hani Alrefai
18/11/2014
Dr. Hani Alrefai 04/11/2014
 Importance
of pentose shunt
 Importance of uronic acid pathway
 Hormonal regulation of blood glucose level
 Causes of hypergylcemia
 Types of DM
 Metabolic changes of DM
 Complications of DM
 Diagnosis of DM
Dr. Hani Alrefai 04/11/2014
 Def..:
It is a pathway by which glucose is converted to
pentose phosphate with production of two
molecules of NADPH.H+.
 Site:
Occurs in cytoplasm of many tissues include liver,
adipose tissues, adrenals, ovaries, testis, red
cells and retina.
Dr. Hani Alrefai 04/11/2014
I- HMP can account for complete oxidation of
glucose and giving 12 molecules of NADPH
A- Reduction of oxidised glutathione
B- Synthesis of : FA, Cholesterol and sphingolipids
C- Activation of folic acid
II- It provides the body with ribose-5phosphate:


Synthesis of nucleotides and nucleic acids.
Synthesis of co-enzymes, NAD and FAD
Dr. Hani Alrefai 04/11/2014
 Due
to genetic deficiency of glucose-6phosphate dehydrogenase (G6PD); the red
blood cell capacity to protect itself from
oxidative damage is markedly decreased (due
to decreased concentration of NADPH).
 Administration of certain drugs (premaquine,
aspirin or sulfonamides), which stimulate the
production of H202 or eating Fava beans
(contain oxidizing agents) produce lysis of
the fragile red cells.
 The only treatment is to avoid the above
factors and by blood transfusion during the
attack of haemolysis.
Dr. Hani Alrefai 04/11/2014
 Definition:
It is an alternative pathway for
glucose oxidation resulting in production of
glucuronic acid.
 Site: It occurs mainly in the cytosol of liver
cells.
 Importance: production of UDP-Glucuronic a


Biosynthesis of mucupolysaccharides
Detoxication of : - Steroids
- Drugs
- Bilirubin
Dr. Hani Alrefai 04/11/2014
Insulin
Glucagon
Adrenalin
Glucocorticoids
GH
Thyroid hormones
Dr. Hani Alrefai 04/11/2014
Insulin:
leads to decrease of blood glucose level
A.






↓↓Gluconeogenesis
↑↑ Glucose entrance to the cells and oxidation.
↑↑glycogenesis (ms. & liver)---↓↓Glycogenolysis
↑↑ Lipogenesis ----------------------↓↓ lipolysis
↑↑ Protein synthesis
↓↓Ketogenesis
Dr. Hani Alrefai 04/11/2014
Glucagon:
B.


↑↑Gluconeogenesis(in the liver only)
↑↑Glycogenolysis ----------------↓↓glycogenesis
Adrenaline:
C.



↑↑Gluconeogenesis
↑↑Glycogenolysis ----------------↓↓glycogenesis
↓↓ Insulin secretion.
Growth hormone:
E.


↓↓ Glucose uptake by the tissues.
↑↑ Lipolysis which ↑↑ FFA leading to ↓↓ glucose utilization
(glucose sparing effect)
Glucocorticoids:
D.


↑↑ Gluconeogenesis
Facilitate the action of glucagons, adrenaline and
growth H.
Dr. Hani Alrefai 04/11/2014

Def.
It is the rise of blood glucose level above the normal level.

Causes

Deficiency of insulin:



Increase of anti-insulin hormones:





Diabetes mellitus.
Pancreatictomy (total or subtotal).
Adrenaline as in emotion or in case of pheochromocytoma
Glucocorticoids as in adrenal tumors and Cushing syndrome.
Thyroxin as in hyperthyroidism.
Pituitary growth hormone as in acromegally.
Alimentary causes:
It is due to increased rate of glucose absorption as in case of
gastrectomy.
Dr. Hani Alrefai 04/11/2014

Def:
It is a state of chronic hyperglycemia due to
disturbances in carbohydrate Lipid and protein
metabolism.

Types:

Primary



Type I (insulin dependent diabetes mellitus or IDDM)
Type II (non-insulin dependent diabetes mellitus or
NIDDM)
Secondary




Adrenaline in case of pheochromocytoma
Glucocorticoids as in adrenal tumors and Cushing
syndrome.
Thyroxin as in hyperthyroidism.
Pituitary growth hormone as in acromegally.
Dr. Hani Alrefai 04/11/2014
NIDDM
IDDM
1.
2.
3.
4.
It was termed juvenile onset
diabetes and usually occurs
before the age of 20 years.
Most probably, it is an
autoimmune disease causing
destruction of pancreatic (β
cells).
↓↓ insulin level
Treatment is insulin injections
1.
2.
3.
4.
Adult onset diabetes mellitus,
usually develops after the age of
40.
It is caused by either defective
insulin secretion or improper
insulin receptors.
↑↑, ↓↓ or normal insulin level
These cases are usually treated
by oral hypoglycemic drugs.
- Obesity and hyperinsulinism may
be present in this type.
- Hyperglucagonemia is reported in
many cases.
Dr. Hani Alrefai 04/11/2014
1- Hyperglycemia (hyperglycemia is ↑ ↑ bl.glucose more
than 180 mg/dL). it is due to:
- ↓↓ glucose utilization by different tissues.
- ↓↓ rate of glucose transport to certain tissues as muscles
and adipose tissues.
- ↓↓ glycogenesis
-↑↑ gluconeogenesis.
2- Glucosuria, polyuria, polydepsia and polyphagia.
-↑ glucose loss in urine --> ↑ sp. gravity of urine --> ↑ urine
excretion
-Polyurea is associated with loss of H2O soluble vitamins
as well as electrolytes as K+, Na+.
3- ↑ rate of catabolism of triglycerides with
mobilization of free fatty acids from adipose tissues -> loss of weight.
Dr. Hani Alrefai 04/11/2014
4- ↑↑ fatty acids oxidation --> ↑ ketone bodies formation -*
ketonemia and ketonurea with acidosis.
5- ↑↑ protein catabolism --> muscle wasting.
6- ↓↓ protein synthesis --> ↓↓ antibodies formation --> the
patients liable for infections and poor wound healing.
7- A number of tissues don't require insulin for the entry of
glucose into cells --> hence the intracellular glucose of
the tissues attains a level similar to that of blood, then
excess glucose can be reduced to sorbital by
aldose'reductase and part of it is oxidized to fructose by
sorbital dehydrogenase. Large amounts of sorbitol and
fructose inside the cells will causing hypertonicity and
water retention.
These are associated with pathological complication of D.M.
as cataract, neuropathy, nephropathy and retinopathy.
Dr. Hani Alrefai 04/11/2014
1-The glucose tolerance test
2- Glycated haemoglobin
3- Glycated plasma proteins
4- Microalbuminuria
Dr. Hani Alrefai 04/11/2014
 Rational
of test
 Performance of the test
 Results and interpretation
Dr. Hani Alrefai 04/11/2014
Dr. Hani Alrefai 04/11/2014
1.
2.
3.
4.
5.
Diabetic nephropathy.
Diabetic neuropathy.
Diabetic retinopathy.
Cataract
Peripheral vascular disease.
Osmotic
pressure
Dr. Hani Alrefai 04/11/2014
Micro
vasculopathy
Dr. Hani Alrefai 04/11/2014