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 mg per desi liter (500/ /180 mmol / l). Depend on the intake of food before the test. Patients do not febrile, not in stress.

Plasma glucose (mmol/l) 0 8 am 6 pm noon midnight Time of day Plasma insulin (pmol/l) Glucose Insulin meals Blood glucose levels are relatively constant

There is also an opinion that under the normal curve 160 mg/100 ml one hour and 120 mg/100 ml two hours after administration of glucose.

BLOOD GLUCOSE LEVELS Sources: 1) Food 2) Gluconeogenesis 3) 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 Glycogen Gluconeogenesis adipocytes liver 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.

Glycogen n Glycogen n -1 G-1P  G-6P  G ( in the Liver ) +

Other hormones (in addition to glucagon and epinephrine) affecting blood glucose levels: Insulin GH ACTH Cortisol Thyroid

INSULIN Secreted in inactive form Proinsulin C peptide + insulin  C peptide is more easily measured Substances 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 peptide Proinsulin Insulin MW  Ca 2+ -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: mg / dl. Glucosuria occurred Tubule reabsorption capability 350 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 acid Heart 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 intolerance Sorbitol: ↑ peristalsis Diabetes Mellitus: ↓ glucose utilization

Hemolytic can be caused by deficiency of the following enzymes: PFK-1 (phosphofructo kinase-1) Pyruvate kinase G6PD (glucose 6 phosphate dehydrogenase) High dietary fructose or fructose infusion can cause: ↓ inorganic phosphate (Pi)  ↓ ATP synthesis Decreases in inhibition of Purine synthesis by ATP   ↑ Uric acid (uric acid)