Transcript Regulation of Blood Glucose Levelx

Regulation of
Blood Glucose Level
Peshawar Medical College
Learning Objectives

To define what is normal blood glucose level

To describe the sources and utilization of glucose

To identify different factors & explain their role in
regulation the blood glucose level
Regulation of Blood Glucose Level

Normal Range
4.5 – 5.5 mmol/L
(70 – 100 mg / dL)

After carbohydrate meal
6.5 – 7.2 mmol/L
(105– 130 mg/dL)

During starvation
3.3 – 3.9 mmol/L
(60 – 70 mgl/dL)
Regulation of Blood Glucose Level

Fasting & Postpradinal state

Sudden decrease in blood glucose level causes convulsions
(due to diminished supply of glucose to brain)

Much lower levels can be tolerated, provided progressive
adaptation is allowed.
Sources Of Blood Glucose
1) DIET
Polysaccharides/
Disaccharides /
Monosaccharides
GIT
Glc, Fr, Gal
Portal Circulation
Glc
Liver
Glc  Fr
Glc  Gal
Sources Of Blood Glucose
2) GLYCOGENOLYSIS
Glycogen  Glc – I – P  Glc – 6 – P  Glc
(Liver)
3) GLUCONEOGENESIS (Liver & Kidney)
from glycogenic compounds – 2 types
Type-1: Direct conversion of non-carbohydrates to glucose
like amino acids, propionate
(through TCA cycle & reversal of glycolysis)
Sources Of Blood Glucose
Type-2: Those which are the products of
partial breakdown of glucose e.g.
(i) Cori Cycle
Glc
RBCs & Muscles
Anaerobic glycolysis
Lactate  Liver  Pyruvate
Glucose
Energy from Fatty Acids
Gluconeogenesis
Sources Of Blood Glucose
(ii) Glycerol
Glc
Glycolysis
Glucose
Gly.3.P  Glycerol
Gluconeogenesis
Adipose Tissue
Lipogenesis
Liver & Kidney  Glycerol
TAG
Lipolysis
(iii) Glc-alanine Cycle
Gluconeogenesis
Muscle
Glc Glycolysis Pyurvate
Transamination
Alanine  Liver  Glucose
Utilization
Oxidation of glucose for
energy
Sources
Diet / Absorption from
intestine
Glycogenesis
Hepatic Glycogenolysis
Lipogenesis
Glc obtained from other
carbohydrates
Gluconeogenesis (liver)
(liver/muscle)
Blood Glucose
60–90 mg/dl
(Adipose tissue)
Synthesis of
Glycoproteins
 Glycolipids
 Lactose
 Ribose etc

If conc. exceeds
renal threshold
(180 mg/dL)
Excreted in urine
Metabolic & Hormonal Control
(Regulation)

Liver cells and pancreatic  islets are permeable to
glucose via GLUT 2

Cells of all other tissues are relatively impermeable to
glucose and their glucose uptake is regulated by insulin
Metabolic & Hormonal Control
(Regulation)

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HORMONES
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Insulin

Glucagon

Epinephrine and nor-epinephrine

Growth hormone
ENZYMES (e.g. glucokinase) take part in regulating
blood glucose level within a narrow limit.
Metabolic & Hormonal Control
(Regulation)
INSULIN
Produced by -Cells of the islets of Langerhans as a
result of hyperglycemia, since these cells are freely
permeable to Glc via GLUT 2 transporter
Glc
GLUT 2
Cells  Glc
Glucokinase
 ATP  Citric acid Cycle  Glycolysis
Glc – 6 – P
RELEASE OF INSULIN

Increase in ATP inhibits ATP-sensitive K+ channels
leading to increased Ca++ Ions 
Stimulating exocytosis of insulin

Sulfonylurea drugs increase the secretion of insulin by
the same mechanism

Amino acids, FFA, Ketone bodies etc cause the release
of insulin from pancreas
ACTION OF INSULIN

Insulin  Recruitment of GLUT 4   Uptake of glucose
by adipose tissue and muscle

Insulin has no effect on hepatic uptake of glucose but
has an indirect effect by influencing the synthesis of
enzymes involved in
glycolysis ()
glycogenesis () and
gluconeogenesis ()
Hyperglycemic Factors
GLUCAGON:


Secreted by  cells of islets of Langerhans of pancreas
as a result of hypoglycemia
Via portal vein  Liver  activates Phosphorylase 
hepatic glycogenolysis
Hyperglycemic Factors
GLUCAGON (Contd.):

No effect on muscle phosphorylase

Glucagon also enhances gluconeogenesis from
amino acids and lactate
Net Effect:
 Hepatic glycogenolysis & gluconeogenesis 
Hyperglycemic effect
Hyperglycemic Factors
GROWTH HORMONE

Hypoplycemia  Ant. Pituitary gland  Growth hormone (GH)
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GH  ed glucose uptake in certain tissues (like muscle)
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GH  indirect effect by mobilization of FFA from adipose tissue
Net Effect:

Glucose sparing action ---- Hyperglycemic effect
Hyperglycemic Factors
GLUCOCORTICOIDS (CORTISOL)
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Produced by adrenal cortex
Cortisol  increased protein catabolism  increased
activity of enzymes  increased Gluconeogenesis
It also inhibits the utilization of glucose in extra-hepatic
tissues (glucose sparing action)
Hyperglycemic Factors
EPINEPHRINE / NOR – EPINEPHRINE
Fear, excitement, hemorrhage, hypoxia, hypoglycemia
adrenal cortex  Epinephrine / Nor-Epinephrine 
increased cAMP 
activation of Phosphorylase (muscle & liver) 
increased Glycogenolysis
Hyperglycemic Factors
THYROID HORMONES
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Hyperglycemic effects through experimental evidence
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T4 has diabetogenic action since
i.
Thyroidectomy inhibits the development of diabetes
ii.
Glycogen is absent in the livers of thyrotoxic animals
iii.
Humans
a.
b.
Hyperthyroid patients have ed fasting blood
glucose level
Hypothyroid patients have ed fasting blood
glucose level
Role of enzymes in Blood Glucose
Regulation
GLUCOKINASE & HEXOKINASE
LIVER
EXTRAHEPATIC
Glucose
Glucokinase
Glc.6.P
Glucose
Hexokinase
Glc.6.P
Role of enzymes in Blood Glucose
Regulation

Glc.6.P can inhibit Hexokinase but not Glucokinase,
thus hepatic glucose uptake is not affected by
concentration of Glc.6.P

Glucokinase has high Km value or low affinity for
glucose thus its activity increases at higher concentration
of glucose
Role of enzymes in Blood Glucose
Regulation
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When Hyperglycemia 
hepatic glucose uptake is increased
but glucose output is decreased
Hypoglycemia  liver is net producer of glucose
(decreased uptake and increased output)
During hypoglycemia – Hexokinase can function in the
extra-hepatic tissues as it has low Km and high affinity
for glucose
Synthesis of Lactose (Mammary glands)