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Blood Glucose Regulation
Dr.S.Sethupathy
Professor of Biochemistry,
RMMC ,AU
Blood Glucose Regulation
Hypoglycemia kills the patient
immediately whereas
hyperglycemia kills slowly by
producing complications and
organ failure
So it is essential to maintain
blood glucose at optimum level
Fasting plasma glucose is
70-100 mg/dl (after 12-14
hrs fasting). When plasma
glucose estimated by
enzymatic method drops
below 40 mg/dl results in
hypoglycemia
When fasting plasma glucose
level is 101-125 mg/dl, it is
called impaired fasting glucose
and when more than 126 mg/dl
it is labeled as diabetes mellitus
After a meal, blood glucose
raises and it is normally less
than 140 mg/dl at 2 hrs (post
prandial).If it is between 141
and 200 mg/dl, it is called as
impaired glucose tolerance. If it
is more than 200 mg/dl, it is
labeled as diabetic .
How blood glucose is brought down
to normal level in fed state?
1. By transport of glucose into the
cells
Glut-2 transporter in liver is freely
permeable to glucose.
Insulin increases the transport of
glucose across cell membranes of
adipose tissue and muscle by
stimulating glut-4-transporter
2. Stimulation of glycolysis
In liver, insulin increases the
glycolysis by inducing the
synthesis of the following
enzymes
Glucokinase
Phosphofructokinase-1
Pyruvate kinase
Stimulation of glycogenesis
In liver and muscle, insulin stimulates
glycogenesis by activating glycogen
synthase through dephosphorylation of
the enzyme.
Stimulation of lipogenesis
Insulin stimulates the acetyl-CoA-
carboxylase, the rate limiting enzyme in
fatty acid synthesis mainly in liver, and to
a lesser extent in adipose tissue.
Stimulation of protein synthesis
Insulin increases protein synthesis.
How blood glucose level is maintained
normally in fasting state ?
Reduction of Uptake of glucose by less
vital tissues
Due to low insulin level, glucose uptake
by muscle and adipose tissue is reduced
due to inhibition of glut-4-transporter
Stimulation of glycogenolysis
Glucagon through its receptors in liver
cells activates phosphorylase enzyme
through cyclic AMP.
Epinephrine also activates
phosphorylase in liver and
muscle through cAMP
Both glucagon and epinephrine
inhibit glycogenesis by
phosphorylating the enzyme
glycogen synthase.
Thyroxin also increases hepatic
glycogenolysis.
Stimulation of gluconeogenesis
Glucagon stimulates gluconeogenesis
from amino acids through alanine-
glucose cycle
Lactate forms glucose in liver through
Cori cycle - Lactate-glucose cycle
Epinephrine promotes glycogenolysis
in muscle and on catabolism, lactate
produced is carried to liver for
gluconeogenesis
Glucocorticoids increase protein
catabolism to provide glucogenic amino
acids for gluconeogenesis and it also
increases the hepatic uptake of amino
acids
Glucocorticoids also inhibit the
utilization of glucose by extra hepatic
tissues.
Growth hormone decreases glucose
uptake by muscle and ACTH decreases
glucose utilization by the peripheral
tissues
Renal control mechanism
The capacity of renal tubular system to
reabsorb glucose is limited to a rate of
about 350 mg/min known as tubular
maximum for glucose (TMG)
If the blood glucose level goes beyond
160 - 180 mg/dl complete renal tubular
reabsorption does not occur and so
glucose appears in urine. This range of
blood glucose level is known as renal
threshold value for glucose
Glycosuria
Excretion of detectable amount of sugar in
urine. It includes glucosuria, fructosuria,
galactosuria, lactosuria, pentosuria
Glucosuria
Excretion of detectable amount of glucose
in urine.
Alimentary glucosuria
A rapid and transitory rise in blood
glucose due to rapid absorption of glucose
in the intestine after a meal result in
glucosuria. It is harmless.
e.g. In patients with partial gastrectomy
Renal glucosuria
This is due to lowered renal threshold
for glucose resulting in impaired
tubular reabsorption of glucose. It is
harmless. Blood glucose level will be
normal in these patients.
Diabetic glucosuria
This is due to hyperglycemia
Summary
Insulin decreases blood glucose level by
1. Increasing glycolysis
2. Increasing glycogenesis
3. Increasing lipolysis
4. Increase glucose uptake by muscle and
adipose tissue via GLUT-4
Glucagon and epinephrine
• These hormones increase blood glucose level
by
• Increasing glycogenolysis
• Increasing gluconeogenesis
• Increase lipolysis
Oral Glucose Tolerance Test
It is the test to assess the ability an
individual to metabolize a particular
local of glucose which reflected by
changes in the blood glucose level. It
is useful to diagnose early cases of
diabetes mellitus and for known
cases of diabetes mellitus, it is not
required .
Procedure
• On high carbohydrate for 3 days prior to the
test
• Fasting blood sample (10-12 hours of fasting)
is drawn
• 75 gms glucose in 300 ml water to be taken
orally in 5-10 mins
• Blood and urine samples are collected every ½
hr for 2 hours
• Blood glucose is estimated
• Urine is tested for glucose
Normal Diabetes
• OGTT CURVE
•
•
250-
•
• 200-
• 180 -
•
150-
•
• 100-
•
• 50-
•
• 0
• -ve ½ 1 11/2 2 Time (Hrs)
• urine Sugar -ve -ve -ve -ve
•
Diabetes
• OGTT CURVE
•
•
250-
•
• 200-
• 180 -
•
150-
•
• 100-
•
• 50-
•
• 0
• -ve ½ 1 11/2 2 Time (Hrs)
• urine Sugar -ve +ve +ve +ve
•
Renal Glucosuria
• OGTT CURVE
•
•
250-
•
• 200-
• 180 -
•
150-
•
• 100-
•
• 50-
•
• 0
• -ve ½ 1 11/2 2 Time (Hrs)
• urine Sugar -ve +ve -ve -ve
•
Thank you

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Blood glucose regulation

  • 2. Blood Glucose Regulation Hypoglycemia kills the patient immediately whereas hyperglycemia kills slowly by producing complications and organ failure So it is essential to maintain blood glucose at optimum level
  • 3. Fasting plasma glucose is 70-100 mg/dl (after 12-14 hrs fasting). When plasma glucose estimated by enzymatic method drops below 40 mg/dl results in hypoglycemia
  • 4. When fasting plasma glucose level is 101-125 mg/dl, it is called impaired fasting glucose and when more than 126 mg/dl it is labeled as diabetes mellitus
  • 5. After a meal, blood glucose raises and it is normally less than 140 mg/dl at 2 hrs (post prandial).If it is between 141 and 200 mg/dl, it is called as impaired glucose tolerance. If it is more than 200 mg/dl, it is labeled as diabetic .
  • 6. How blood glucose is brought down to normal level in fed state? 1. By transport of glucose into the cells Glut-2 transporter in liver is freely permeable to glucose. Insulin increases the transport of glucose across cell membranes of adipose tissue and muscle by stimulating glut-4-transporter
  • 7. 2. Stimulation of glycolysis In liver, insulin increases the glycolysis by inducing the synthesis of the following enzymes Glucokinase Phosphofructokinase-1 Pyruvate kinase
  • 8. Stimulation of glycogenesis In liver and muscle, insulin stimulates glycogenesis by activating glycogen synthase through dephosphorylation of the enzyme. Stimulation of lipogenesis Insulin stimulates the acetyl-CoA- carboxylase, the rate limiting enzyme in fatty acid synthesis mainly in liver, and to a lesser extent in adipose tissue. Stimulation of protein synthesis Insulin increases protein synthesis.
  • 9. How blood glucose level is maintained normally in fasting state ? Reduction of Uptake of glucose by less vital tissues Due to low insulin level, glucose uptake by muscle and adipose tissue is reduced due to inhibition of glut-4-transporter Stimulation of glycogenolysis Glucagon through its receptors in liver cells activates phosphorylase enzyme through cyclic AMP.
  • 10. Epinephrine also activates phosphorylase in liver and muscle through cAMP Both glucagon and epinephrine inhibit glycogenesis by phosphorylating the enzyme glycogen synthase. Thyroxin also increases hepatic glycogenolysis.
  • 11. Stimulation of gluconeogenesis Glucagon stimulates gluconeogenesis from amino acids through alanine- glucose cycle Lactate forms glucose in liver through Cori cycle - Lactate-glucose cycle Epinephrine promotes glycogenolysis in muscle and on catabolism, lactate produced is carried to liver for gluconeogenesis
  • 12. Glucocorticoids increase protein catabolism to provide glucogenic amino acids for gluconeogenesis and it also increases the hepatic uptake of amino acids Glucocorticoids also inhibit the utilization of glucose by extra hepatic tissues. Growth hormone decreases glucose uptake by muscle and ACTH decreases glucose utilization by the peripheral tissues
  • 13. Renal control mechanism The capacity of renal tubular system to reabsorb glucose is limited to a rate of about 350 mg/min known as tubular maximum for glucose (TMG) If the blood glucose level goes beyond 160 - 180 mg/dl complete renal tubular reabsorption does not occur and so glucose appears in urine. This range of blood glucose level is known as renal threshold value for glucose
  • 14. Glycosuria Excretion of detectable amount of sugar in urine. It includes glucosuria, fructosuria, galactosuria, lactosuria, pentosuria Glucosuria Excretion of detectable amount of glucose in urine. Alimentary glucosuria A rapid and transitory rise in blood glucose due to rapid absorption of glucose in the intestine after a meal result in glucosuria. It is harmless. e.g. In patients with partial gastrectomy
  • 15. Renal glucosuria This is due to lowered renal threshold for glucose resulting in impaired tubular reabsorption of glucose. It is harmless. Blood glucose level will be normal in these patients. Diabetic glucosuria This is due to hyperglycemia
  • 16. Summary Insulin decreases blood glucose level by 1. Increasing glycolysis 2. Increasing glycogenesis 3. Increasing lipolysis 4. Increase glucose uptake by muscle and adipose tissue via GLUT-4
  • 17. Glucagon and epinephrine • These hormones increase blood glucose level by • Increasing glycogenolysis • Increasing gluconeogenesis • Increase lipolysis
  • 18. Oral Glucose Tolerance Test It is the test to assess the ability an individual to metabolize a particular local of glucose which reflected by changes in the blood glucose level. It is useful to diagnose early cases of diabetes mellitus and for known cases of diabetes mellitus, it is not required .
  • 19. Procedure • On high carbohydrate for 3 days prior to the test • Fasting blood sample (10-12 hours of fasting) is drawn • 75 gms glucose in 300 ml water to be taken orally in 5-10 mins • Blood and urine samples are collected every ½ hr for 2 hours • Blood glucose is estimated • Urine is tested for glucose
  • 20. Normal Diabetes • OGTT CURVE • • 250- • • 200- • 180 - • 150- • • 100- • • 50- • • 0 • -ve ½ 1 11/2 2 Time (Hrs) • urine Sugar -ve -ve -ve -ve •
  • 21. Diabetes • OGTT CURVE • • 250- • • 200- • 180 - • 150- • • 100- • • 50- • • 0 • -ve ½ 1 11/2 2 Time (Hrs) • urine Sugar -ve +ve +ve +ve •
  • 22. Renal Glucosuria • OGTT CURVE • • 250- • • 200- • 180 - • 150- • • 100- • • 50- • • 0 • -ve ½ 1 11/2 2 Time (Hrs) • urine Sugar -ve +ve -ve -ve •