Cho metabolism by dr naglaa ibrahim azab assistant professor of medical biochemistry
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CHO METABOLISM BY Dr. Naglaa Ibrahim Azab Assistant professor of medical biochemistry. BLOOD GLUCOSE HOMEOSTASIS (Regulation of blood glucose level). What is glucose homeostasis???. It is the maintenance of blood glucose level within the normal range .

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CHO METABOLISM BY Dr. Naglaa Ibrahim Azab Assistant professor of medical biochemistry

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Cho metabolism by dr naglaa ibrahim azab assistant professor of medical biochemistry

CHO METABOLISM

BY Dr. Naglaa Ibrahim Azab

Assistant professor of medical biochemistry


Blood glucose homeostasis regulation of blood glucose level

BLOOD GLUCOSE HOMEOSTASIS(Regulation of blood glucose level)


Cho metabolism by dr naglaa ibrahim azab assistant professor of medical biochemistry

What is glucose homeostasis???

It is the maintenance of blood glucose level within the normal range


Cho metabolism by dr naglaa ibrahim azab assistant professor of medical biochemistry

Normal blood glucose level (mg/dl)

Fasting

(6-12 h after meals)

70-110(126)

130-150

1 h after CHO meals

2 h after CHO meals

70-110(126)

Starvation

(prolonged fasting)

60-70


Cho metabolism by dr naglaa ibrahim azab assistant professor of medical biochemistry

Importance of glucose homeostasis

Maintain a continuous supply of sufficient blood glucose to the

brain and CNS

Sudden hypoglycemia (< 40 mg/dl)

lead to????

Coma and even death


Cho metabolism by dr naglaa ibrahim azab assistant professor of medical biochemistry

Glycogenolysis

(Liver glycogen)

Gluconeogenesis (mainly from amino acids)

Diet

by digestion and absorption

Main source during prolonged starvation

(> 18 hrs)

Source during

early fasting

(12- 18 hrs)

mostly

Blood glucose

Uptake by

Tissues

as muscles, adipose tissue & brain

Oxidation

glycogenesis

lipogenesis


Cho metabolism by dr naglaa ibrahim azab assistant professor of medical biochemistry

  • How to maintain the balance between addition and removal of glucose???

  • (What are the factors important for maintaining glucose homeostasis

  • What are the factors that regulate blood glucose level????

tissues

hormones


Cho metabolism by dr naglaa ibrahim azab assistant professor of medical biochemistry

Tissues regulating blood glucose level

Muscles and adipose tissues

GIT

Liver

Kidney


Cho metabolism by dr naglaa ibrahim azab assistant professor of medical biochemistry

GIT

Maximum rate of glucose absorption is 1 gm glucose/Kg body weight / hour → prevents sudden hyperglycemia after meal.

Glucose

\/

\

↑intestinal factors

↑ enterogastrone hormone from duodenum

\

\

  • stimulate insulin secretion from pancreas

  • - - - gastric evacuation


Cho metabolism by dr naglaa ibrahim azab assistant professor of medical biochemistry

Liver

(Blood glucostat)

After CHO diet

Fasting

Uptake

\

Glycogenolysis

\

\

Oxidation

Glucose

\

\

\

Glycogenesis

Gluconeogenesis

LIPOGENESIS

Blood glucose

Blood glucose


Cho metabolism by dr naglaa ibrahim azab assistant professor of medical biochemistry

Muscle &Adipose tissue

After CHO diet

Fasting

Uptake

\

Gluconeogenesis

Muscle:Release alanine to liver

Adipose tissue:by lipolysis release glycerol and f.as

\

Oxidation

Glucose

\

\

\

Glycogenesis in muscle

Lipogenesis

In adipose tissue

Blood glucose

Blood glucose


Cho metabolism by dr naglaa ibrahim azab assistant professor of medical biochemistry

Kidneys

Renal threshold for glucose is 180 mg/dl


Cho metabolism by dr naglaa ibrahim azab assistant professor of medical biochemistry

Hormones


Cho metabolism by dr naglaa ibrahim azab assistant professor of medical biochemistry

Insulin

Uptake (except brain, liver,RBCs- non dependant)

\

\

Glycogenolysis

\

\

\

Oxidation

Glucose

\

\

\

Glycogenesis

Gluconeogenesis

\

LIPOGENESIS

Lipolysis

Blood glucose


Cho metabolism by dr naglaa ibrahim azab assistant professor of medical biochemistry

Glucagon and adrenaline

Uptake

\

Glycogenolysis

\

\

\

\

Oxidation

Glucose

\

\

\

Glycogenesis

Gluconeogenesis

\

LIPOGENESIS

Lipolysis

Blood glucose


Cho metabolism by dr naglaa ibrahim azab assistant professor of medical biochemistry

Clucocorticoids and G.H.

Uptake

\

\

\

Glucose

Gluconeogenesis

\

\

Oxidation

\

\

a.as

( glucocorticoids)

Lipolysis ( G.H)

Blood glucose


Cho metabolism by dr naglaa ibrahim azab assistant professor of medical biochemistry

Thyroid hormones

Uptake

Absorption

\

\

\

\

\

\

Glycogenolysis

Oxidation

Glucose

\

\

\

Glycogenesis

Gluconeogenesis

LIPOGENESIS

Blood glucose


Glucosuria

Glucosuria


Cho metabolism by dr naglaa ibrahim azab assistant professor of medical biochemistry

Presence of detectable amounts of glucose in urine (> 0.5 g/day, normally < 150 mg/day).


Cho metabolism by dr naglaa ibrahim azab assistant professor of medical biochemistry

Causes:

I. Hyperglycemic glucosuria:

1) Diabetes mellitus glucosuria

2)Adrenaline glucosuria

- Pheochromocytoma.

-Emotions.

-Stress (oral examination).

-Hypotension

-Injection

3) Alimentary glucosuria: It is due to intake of large amounts of glucose after prolonged carbohydrate deprivation.


Cho metabolism by dr naglaa ibrahim azab assistant professor of medical biochemistry

Causes:

II. Renal glucosuria (plasma glucose < 180 mg/dl):

1)Congenital glucosuria : = renal diabetes = Diabetes innocence = benign glucosuria.

2) Pregnancy glucosuria : Occurs in about 20% of normal pregnancies.

3) Nephritis & Nephrosis : Only some cases show glucosuria.

4) PhlorrhizinGlucosuria : Phlorrhizin inhibits renal tubular reabsorption of glucose.


Diabetes me llitus

Diabetes mellitus


Cho metabolism by dr naglaa ibrahim azab assistant professor of medical biochemistry

DM

hyperglycemia

\

\

\

\

glucosuria

syndrome

\

\

polyuria

\

\

\

polydepsia

polyphagia

Loss of weight


Cho metabolism by dr naglaa ibrahim azab assistant professor of medical biochemistry

Causes

↓insulin level or insulin resistance

↑anti-insulin hormones

(glucagon, adrenalin )

Types

Type I:

Insulin dependent DM =IDDM

= Juvenile diabetes.

Type II:

Non Insulin dependent DM =NIDDM

= Maturity onset DM


Cho metabolism by dr naglaa ibrahim azab assistant professor of medical biochemistry

Metabolic changes in DM

1-Disturbed Carbohydrates metabolism:

hyperglycemia due to

-Decreased glucose uptake and utilization by tissues.

-Decreased glycogenesis &lipogenesis.

-Increased glycogenolysis &gluconeogenesis.

2-Disturbed lipid metabolism:

hyperlipidemia and hypercholesterolemia due to

-Increased lipolysis and plasma FFA

-Increased ketogenesis: which may cause ketoacidosis


Cho metabolism by dr naglaa ibrahim azab assistant professor of medical biochemistry

Metabolic changes in DM

3-Disturbed protein metabolism:

Negative nitrogen balance ,wasting ,weakness of muscle and delayed healing of wounds due to

-Decreased protein anabolism.

-Increased protein catabolism.

  • 4-Disturbed water and electrolyte balance:

  • Glucosuria→ osmotic dieresis → polyuria → dehydration → polydepsia

  • Increased loss of Na+ & K + in urine.


Cho metabolism by dr naglaa ibrahim azab assistant professor of medical biochemistry

Complications of DM

  • 1-Macrovascular complications of DM:

  • (atherosclerosis, hypertension, myocardial infarction and renal failure).

  • Most of these complications are due to damage of the large blood vessels by glycosylation of protein molecules in the wall of blood vessels secondary to hyperglycemia.

  • The presence of hypercholesterolemia and hyperlipoproteinemia increase the risk for the development of atherosclerosis and its complications.

2- Microvascular complications:

They affect the small blood capillaries and lead to : Diabetic retinopathy and neuropathy .

These are due to vascular damage caused by protein glycation and sorbitol (the alcohol of glucose ) accumulation.


Cho metabolism by dr naglaa ibrahim azab assistant professor of medical biochemistry

Complications of DM

3- Diabetic cataract :

It usually occurs in young age .

It is due to accumulation of sorbitol in the eye lens, which leads to osmotic accumulation of fluid in the lens lead to its opacity.

4-Diabetic coma:

Coma is loss of consciousness. There are many types of coma.


Cho metabolism by dr naglaa ibrahim azab assistant professor of medical biochemistry

Differences between hyperglycemic and hypoglycemic coma


Cho metabolism by dr naglaa ibrahim azab assistant professor of medical biochemistry

  • Treatment of coma

  • hyperglycemic coma treated by

  • insulin and glucose intravenous to avoid sever drop of blood glucose

  • correction of electrolyte imbalance resulting from acidosis and polyuria .

  • hypoglycemic coma treated by

  • glucose infusion.


Cho metabolism by dr naglaa ibrahim azab assistant professor of medical biochemistry

Diagnosis of DM

1- By measuring the blood glucose level in fasting( 8-12 h) state and two-hour postprandial blood glucose level.

a)Normally:

Fasting blood sugar = 70 – 110 mg/dl.

2-hours postprandial = up to 140 mg/dl.

b)In Diabetics:

Fasting blood glucose = > 140 mg/dl.

2-hours postprandial = > 200 mg/dl.


Cho metabolism by dr naglaa ibrahim azab assistant professor of medical biochemistry

Diagnosis of DM

  • 2- Oral glucose tolerance test (OGTT):

  • After fasting 8-12 hours, the patient is given 70 gm D-glucose (1 g/Kg body weight) in a cup of water

  • Blood and urine samples are taken fasting, ½, 1, 1½, 2, 2½ hours.

  • -Samples are analyzed for glucose.

  • -A blood sugar curve is plotted.


Cho metabolism by dr naglaa ibrahim azab assistant professor of medical biochemistry

Diagnosis of DM


Cho metabolism by dr naglaa ibrahim azab assistant professor of medical biochemistry

Diagnosis of DM

Comments on normal & abnormal oral glucose tolerance curves


Cho metabolism by dr naglaa ibrahim azab assistant professor of medical biochemistry

Diagnosis of DM

  • In normal persons:

  • fasting 70 – 120 it increases after 1 hour and returns back to fasting after 2 hours:

  • •The blood glucose never exceeds 170 mg/dl.

  • •No glucosuria.

  • In Diabetes mellitus:

  • the fasting is more than normal ( > 110 mg/dl or more ) and the curve takes 3 hours or more to return back to fasting level.

  • One or more samples exceed 180 mg/dl.

  • There is glucosuria.


Cho metabolism by dr naglaa ibrahim azab assistant professor of medical biochemistry

Diagnosis of DM

  • 3-Measurement of glycosylated –Hb (HbA1C)

  • Glycosylated Hb (HbA1c) results fromnon enzymatic binding of glucose with Hemoglobin .The process is irreversible and continues during the half life of RBCs.

  • Normal subjects and controlled cases of DM have 4-8% glycosylated –Hb.

  • The increase in the percent of HbA1c is related to the blood glucose level.

  • The test is used for follow up of diabetic patients.

  • Not affected byfasting or feeding or any factor that affect blood glucose immediately so it gives an idea aboutthe glycemic control of the patient throughout the life span of RBCs ( 120 days ).Also it gives an idea aboutthe efficiency of the drugs used in treatment and adjustment of proper dose.


Cho metabolism by dr naglaa ibrahim azab assistant professor of medical biochemistry

Other types of DM

  • 1-Diabetes insipidus: Deficiency of antiduretic hormone (ADH). Urine volume > 10 L/day, watery specific gravity 1003.

  • 2-Steroid diabetes: Long term treatment with glucocorticoids which cause hyperglycemia. Prolonged hyperglycemia causes exhaustion of β-cell of pancreas.

  • 3-Stress diabetes : Due to increased adrenaline in emotional states.

  • 4-Experimental diabetes; could be caused by :

  • • Alloxan

  • •Streptozotocin

  • • Dehydroascorbic acid

  • • Surgically by removal of pancreas


Cho metabolism by dr naglaa ibrahim azab assistant professor of medical biochemistry

Other types of DM

Differences between diabetes mellitus and diabetes insipidus


Hypoglycemia

hypoglycemia


Cho metabolism by dr naglaa ibrahim azab assistant professor of medical biochemistry

It is the decrease of blood glucose level to less than 50 mg /dl.


Cho metabolism by dr naglaa ibrahim azab assistant professor of medical biochemistry

Importance

The CNS is very dependent on a continuous supply of blood glucose as a fuel for energy.


Cho metabolism by dr naglaa ibrahim azab assistant professor of medical biochemistry

Symptoms

Adrenergic symptoms

mediated by epinephrine release

Neuroglycopenicsymptoms (neuroglycopenia)

Mediated by impaired delivery of glucose to the brain

\

\

impairment of brain functions causing headache, confusion ,slurred speech, seizures, coma and even death

  • Anxiety

  • Palpitation

  • Tremors

  • sweating


Cho metabolism by dr naglaa ibrahim azab assistant professor of medical biochemistry

Causes

Overdose of insulin (most common cause)

Fasting hypoglycemia

Postprandial hypoglycemia:

\

\

Alimentary hypoglycemia

due to exaggerated insulin release following a carbohydrates meal or after gastrectomy

Liver cell failure

(no glycogenolysis or gluconeogenesis)

Chronic Alcoholism due to excessive alcohol intake with decreased food intake (no gluconeogenesis)

Hereditary fructose intolerance : Ingestion of sucrose causes hypoglycemia due to accumulation of fructose -1-P which inhibits glycogenolysis by allosteric inhibition of liver phosphorylase enzyme.

Adrenocortical insufficiency (Addison's disease). (glucocorticoids)

Glycogen storage diseases (Von Gierke'sdisease)

G-6-p can not leave liver (no G-6-phosphatase


Cho metabolism by dr naglaa ibrahim azab assistant professor of medical biochemistry

CH3-CH2OH → CH3-CHO  CH3-COOH →ACTIVE ACETATE - - Phosphofructokinase enzyme


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