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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Insulinmeals

Blood glucose levels are relatively constant

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.

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)

Coordination between organs is needed to control blood glucose

levels

Glucose

GlycogenGluconeogenesis

adipocytesliver

muscle

Food consumption

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

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.

Glycogenn

Glycogenn -1

G-1P G-6P G ( in the Liver ) +

Other hormones (in addition to glucagon and epinephrine)affecting blood glucose levels:InsulinGHACTHCortisolThyroid

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.

C peptideProinsulinInsulinMW

Ca2+-dependent endopeptidases

A Chain

B Chain

PC2(PC3)

PC3

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

ACTH (Adreno Cortico Tropic Hormone)

Affect the metabolism of carbohydrates together with GH increase gluconeogenesis

Cortisol: enhance gluconeogenesis

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.

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

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 ).

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

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)