Download - CARBOHYDRATE TOLERANCE
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CARBOHYDRATE TOLERANCE Glucose tolerance is the ability to regulate the
blood glucose concentration after the administration of a test dose of glucose (normally 1 g/kg body weight) Diabetes Mellitus decrease glucose tolerance.
Normal blood glucose levels are 50-100 mg per desi liter (500/180 - 1000/180 mmol / l).
Depend on the intake of food before the test. Patients do not febrile, not in stress.
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Pla
sm
a g
luc
os
e(m
mo
l/l)
0
8 am 8 am6 pmnoon midnight
2
4
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Time of day
0
100
200
300
400
500
Pla
sm
a in
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(pm
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Glucose
Insulinmeals
Blood glucose levels are relatively constant
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There is also an opinion that under the normal curve160 mg/100 ml one hour and120 mg/100 ml two hours after administration of glucose.
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BLOOD GLUCOSE LEVELS
Sources:1) Food2) Gluconeogenesis3) Glycogenolysis
Maintenance of blood glucose by the liver with glycogenolysis and gluconeogenesis, is under hormonal control (glucagon or if blood glucose drops very promptly epinephrine)
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Coordination between organs is needed to control blood glucose
levels
Glucose
GlycogenGluconeogenesis
adipocytesliver
muscle
Food consumption
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Carbohydrate metabolism Glucose turnover (basal state)
55% Oxidation
20% Glycolysis (muscle)
25% Re-uptake
(liver, gut)
10% Muscle
45% Brain
Glucose
75% Glycogenolysis
25% Gluconeogenesis
60% from lactate
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If blood glucose ↓ pancreatic glucagon released, glucagon activates adenylyl cyclase, an enzyme catalyzes formation of cAMP from ATP, cAMP activates the cAMP-dependent protein kinase, which in turn will converts phosphorylase kinase b to phosphorylase kinase a (ATP as phosphate donors). Active phosphorylase kinase catalyzes phosphorylase b to phosphorylase a. Phosphorylase a break down glycogen and generate G 1P. With glucantransferase and debranching enzyme glycogenolysis will proceed until the liver depleted with glycogen. G-1P converted to G-6P and G-6Pase splits the phosphate. Glucose then enters the circulation.
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Glycogenn
Glycogenn -1
G-1P G-6P G ( in the Liver ) +
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Other hormones (in addition to glucagon and epinephrine)affecting blood glucose levels:InsulinGHACTHCortisolThyroid
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INSULIN Secreted in inactive form
Proinsulin C peptide + insulin C peptide is more easily measuredSubstances or chemicals which stimulates insulin secretion:glucose, amino acids, free fatty acids, ketone bodies, glucagon, tolbutamide and secretine.In contrast epinephrine inhibits Insulin secretion
Insulin entrance of G into cells except liver, erythrocytes and neuronal cells.
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C peptideProinsulinInsulinMW
Ca2+-dependent endopeptidases
A Chain
B Chain
PC2(PC3)
PC3
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Growth Hormone:
Growth hormone may affect levels blood glucose by activating Hormone Sensitive Lipase. The resulting fatty acids, and derivatives (acetyl-CoA and ketone compounds) causes inhibition of glucose consumption by peripheral tissues
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ACTH (Adreno Cortico Tropic Hormone)
Affect the metabolism of carbohydrates together with GH increase gluconeogenesis
Cortisol: enhance gluconeogenesis
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Renal function in Carbohydrate Metabolism
As a “safety clap“. If blood glucose ↑ , some will be excreted through the kidneys (renal threshold)Renal threshold: 170 - 180 mg / dl.Glucosuria occurredTubule reabsorption capability350 mg / min.
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Carbohydrate metabolism Glucose turnover (basal state)
55% Oxidation
20% Glycolysis (muscle)
25% Re-uptake
(liver, gut)
10% Muscle
45% Brain
→ Glucose
75% Glycogenolysis
25% Gluconeogenesis
60% from lactate
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Biomedical importance
Normal metabolism: hunger if not prolonged, sports, pregnancy and lactation
Abnormal metabolism: lack of certain foodstuffs, as well as enzyme deficiencies or because of abnormal hormone secretion. The most interesting disease to study is diabetes mellitus ( DM ).
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Glycolysis: Pyruvate kinase enzyme hemolytic anemia.Malignant tumor ↑ lactic acidHeart can not tolerance unaerobic glycolysis
Glycogen: abnormal accumulation of I VIII
Oxidation of pyruvic acid: vitamin deficiency vit. B1 beri-beri
MP Shunt: G6PD deficiency hemolytic
Fructose: Essential Fructosuria, "hereditary" fructose intoleranceSorbitol: ↑ peristalsis
Diabetes Mellitus: ↓ glucose utilization
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Hemolytic can be caused by deficiency of thefollowing enzymes:PFK-1 (phosphofructo kinase-1)Pyruvate kinaseG6PD (glucose 6 phosphate dehydrogenase)
High dietary fructose or fructose infusioncan cause:↓ inorganic phosphate (Pi) ↓ ATP synthesisDecreases in inhibition of Purine synthesisby ATP ↑ Uric acid (uric acid)