Blood glucose homeostasis

BLOOD GLUCOSE HOMEOSTASIS Dr. Vijay Marakala, MBBS, MD.

BIOCHEMISTRYIMS, MSU.

BLOOD GLUCOSE HOMEOSTASIS -OUTLINE

Normal plasma glucose

Factors maintaining

blood glucose

Post-prandial regulation

Regulation during fasting Clinical aspect

BLOOD GLUCOSE HOMEOSTASIS

• Blood glucose level is tightly controlled because the brain constantly needs glucose

• Severe hypoglycemia can cause coma and death • Chronic hyperglycemia results in

Glycation of proteins, Endothelial dysfunction Diabetes

NORMAL VALUES

FASTING BLOOD SUGAR[FBS] /FASTING PLASMA GLUCOSE [FPG]

70-110mg/dL 4-6.1mmol/L

BLOOD GLUCOSE

REGULATION OF BLOOD GLUCOSE

The plasma

glucose level

depends on the

balance between

glucose entering

and leaving the

extracellular fluid GLYCOGENESISGLYCOLYSIS

GLUCONEOGENESISGLYCOGENOLYSIS

LIPOGENESIS

DIET

Use Storage Conversion

Supply

70-110mg/dL 4-6.1mmol/L

FACTORS MAINTAINING BLOOD GLUCOSE

Factors which cause entry ofglucose into blood

• Absorption from intestines• Glycogenolysis• Gluconeogenesis• Hyperglycemic hormones

Factors leading to depletion of glucose in blood

• Utilization by tissues for energy

• Glycogen synthesis• Conversion of glucose into

fat • Hypoglycemic hormone

POST-PRANDIAL REGULATION

GLUCOSEABSORPTION

GLYCOGENESIS

LIPOGENESIS

UTILIZATION BY TISSUE FOR ENERGY GLYCOLYSISTCA CYCLEETC

REGULATION DURING FASTING

GLUCOSE

GLYCOGENOLYSISLIPOLYSIS

GLYCEROL, LACTATE, PYRUVATE, GLUCOGENIC AMINO ACIDS

GLUCONEOGENESIS

FFAALTERNATE

SOURCE OF ENERGY

HORMONAL REGULATION

HYPERGLYCEMIC HORMONES• Glucagon• Cortisol• Epinephrine• Growth hormone

HYPOGLYCEMIC HORMONES• Insulin

HORMONAL REGULATION

The pancreas detects the change in blood glucose concentration and releases the appropriate hormone

High blood glucose

Signal to release

Hypoglycemic hormone

insulin

Low blood glucose

Signal to

release

Hyperglycemic hormone glucagon

HYPERGLYCEMIC HORMONESGLUCAGON Promotes Glycogenolysis, gluconeogenesis

Depresses glycogen synthesis

EPINEPHRINE Promotes Glycogenolysis, gluconeogenesis

Favours uptake of amino acids

CORTISOL Increases gluconeogenesis

Releases amino acids from the muscle

GROWTH HORMONE

Decreases glycolysis

Mobilizes fatty acids from adipose tissue

HORMONAL REGULATION

HORMONAL REGULATION - INSULIN

INSULIN

GLYCOGENESISGLYCOLYSIS

GLUCONEOGENESIS

GLUCOSE UPTAKE IN MUSCLE AND ADIPOSE TISSUE

GLYCOGENOLYSIS LIPOLYSIS

LIPOGENESIS

+ + + +

- --

FED STATE

HORMONAL REGULATION - INSULIN Glucose is diffused into cells through

transporters such as GLUT4 GLUT4 is present in cytoplasmic

vesicles Insulin binding to its receptor causes

vesicles to diffuse into plasma membrane

Brain and liver have non-insulin dependent glucose transporter

FASTING STATE

HORMONAL REGULATION

INSULIN favours glycolysis by activating the key enzymes of glycolysis

GLUCAGON inhibits key enzymes of glycolysis

GlucokinasePhosphofructokinasePyruvate kinase

Insulin & glucagon has opposing action

RENAL REGULATION

Tubular maximum

Renal threshold Glycosuria

Glucosuria Occurs When the Renal Threshold for Glucose Is Exceeded

Glucosuria occurs when the venous blood glucose concentration exceeds 180mg/dL [9.5–10.0 mmol/L]

BLOOD GLUCOSE – CLINICAL ASPECT

Estimation Common terms

Value interpretaio

n

BLOOD GLUCOSE ESTIMATION • The blood is collected using an anticoagulant (potassium

oxalate) and an inhibitor of glycolysis (sodium fluoride).

• Fluoride inhibits the enzyme, enolase, and so glycolysis on the whole is inhibited

• The glucose oxidase (GOD) method is the one most widely used.

NORMAL VALUES- common terms• A FBS is taken after at least eight

hours of fastingFASTING PLASMA

GLUCOSE [FPG/FBS]

• Test done any time of day without regard to time since last meal.

RANDOM PLASMA GLUCOSE [RBS/RPG]

• The test done about 2 hr after a good meal

POST-PRANDIAL BLOOD GLUCOS

[PPBS]

NORMAL VALUES

FASTING FBS

• 70-110mg/dL• 4-6.1mmol/L

RANDOMRBS

• < 140 mg/dl• <7.8 mmol/l

POST-PRANDIALPPBS

• 140 mg/dL• 7.8 mmol/L

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After overnight fast

FPG and urine sample is collected

Give 75gm of anhydrous glucose in about 300ml of water

Blood & urine specimens are collected at after 2hours

Blood tests GLUCOSE TOLERANCE TEST

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The Diabetes Expert Committee criteria for evaluating the standard oral glucose tolerance test.

Normal Glucose Tolerance

Impaired Glucose Tolerance

Diabetes Mellitus

Fasting plasma glucose (mg/dL)

< 110<6.1mmol/L

110–125 ≥126 >7mmol/L

Two hours after glucose load (mg/dL)

< 140<7.8mmol/L

≥140–199 ≥200 >11.1mmol/L

Blood tests GLUCOSE TOLERANCE TEST

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