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1. REGULATION OF BLOOD GLUCOSE

2. Normal Blood glucose levels
Fasting levels: 70-100 mg/dL
Postprandial : up to 140 mg/dL
Maintained with in physiological limits by
1. Rate of Glucose entrance into blood
circulation
2. Rate of its removal from the blood stream.

3. Glucose Concentration
( mg/dl )
200 post prandial level Diagnostic for Diabetics
180 ( Renal thereshold )
Hyperglycemia 140 PP Normal
126 Fasting level Diagnostic for Diabetics
100
Normal (F)
70
Hypoglycemia
40 Hypoglycemic Coma

4. What goes wrong when the concentration
decreases?
Hypoglycaemia
The symptoms associated
with low blood sugar are:
tiredness, confusion,
dizziness, headaches,
mood swings, muscle
weakness, tremors, cold
sweating , irreversible
CNS damage, coma,
death

5. What goes wrong when the concentration
increases too far?
Hyperglycaemia
The symptoms include:
Excessive thirst; frequent urination;
fatigue; weight loss; vision problems, such
as blurring; increased susceptibility to
infections, Dibetes mellitus

6. Rate of glucose entrance in to the blood by:
1. Absorption from intestine
2. Hepatic glycogenolysis
3. Gluconeogenesis
4. Glucose obtained from other carbohydrates,
eg: fructose, galactose etc

7. Rate of Removal of Glucose from blood depends on:
1. Oxidation of glucose by tissue to supply energy
2. Hepatic glycogenesis
3. Glycogen formation in muscles
4. Conversion of glucose to fats in adipose tissues
5. Synthesis/formation of fructose in seminal fluid,
lactose in mammary gland.
6. Formation of ribose sugars and nucleic acid
synthesis.

9. Stages of maintenance of blood
glucose level

10. Absorptive stage
• Absorptive stage starts from feeding and lasts
upto 3-4 hours after meal. During this phase
following activities takes place with regards to
glucose.
• Dietary glucose to liver and then to most
tissue.
• Glucose is used as a fuel by most tissues.
• Excess of glucose is stored as glycogen in liver
and muscles.

11. Post absorptive phase
The post absorptive phase lasts for about 16-18
hours after the absorption(3-4hours after meal) is
completed. The main activities necessary with
regards to glucose are as follows:
• Lever glycogenolysis become the major source of
blood sugar.
• Muscle use its glycogen stores for energy.
• Gluconeogenesis starts gradually and peaks
about 24 hours after the last meal.
• Glycogenolysis starts declining after 16-18 hours
and by about 24-30 hours is negligible.

12. Starvation
• After about 1-11/2 day of the starvation,
gluconeogenesis is the main source of glucose.
• Fatty acids mobilized from adipose tissue become
an alternate fuel for energy for most tissue.
• Lactate and glycerol are reutilized for
gluconeogenesis .ATP produced in fatty acid
oxidation is used in liver for gluconeogenesis and
other body functions.
• High rate of hepatic gluconeogenesis continues
for few days in early starvation.

13. Prolonged starvation
• If starvation continues further beyond 2-3 days and
extend into weeks, hepatic gluconeogenesis decrease
and gluconeogenesis in kidney becomes more
significant.
• Protiens in muscle are broken down to provide
gluconeogenic amino acids. Fats are the energy source
of most tissue.
• If starvation continue beyond without any feeding, lipid
stores are also depleted and several associated
complication, like ketoacidosis, dehydration, etc., occur
ultiemately death follows.

14. Response to low Blood Glucose
In the fasting state there will be decreased blood
glucose levels.
This stimulates the secretion of Glucagon from
pancreas.
The Glucagon released into the blood will stimulate
hepatic glycogenolysis and gluconeogenesis,
there by increasing the blood glucose levels.
Once the blood glucose levels raises to the normal
levels, the stimulus for the release of Glucagon
will diminish.

15. In the post prandial state (after a meal)
 Remember there are two separate signaling events
 First signal is from the ↑ Blood Glucose to pancreas
 To stimulates insulin secretion in to the blood
stream
 The second signal from insulin to the target cells
 Insulin signals to the muscle, adipose tissue and
liver to permit to glucose in and to utilize glucose
 This effectively lowers Blood Glucose
Response to Elevated Blood Glucose

16. Role of Liver and Extrahepatic Tissues
• GLUT-2 is freely permeable to glucose and is the
main hepatic glucose transporter ( None insulin
dependent).
• GLUT-4 is main glucose transporter of extrahepatic
tissues i.e muscle, adipose tissues, etc. ( insulin
dependent).
• Hence,the glucose uptake from blood by
extrahepetic tissues is regulated by insulin. This is
become rate limiting step in glucose utilization in the
absence of insulin.
• But the glucose uptake by liver is independent of
insulin.

17. Role of Hexokinase and Glucokinase
• Liver has glucokinase and hexokinase while most extrahepetic
tissue have only hexokinase.
• Hexokinase is saturable, has low Km for glucose and is
product feed back inhibited.
• Glucokinase is non-saturable , has high Km for glucose and not
product feed back inhibited.
• Liver continues to have high glucose uptake during
hyperglycaemia.
• Extrahepatic tissue is product feed back inhibited due to
accumulation of glucose-6-phosphate even though insulin is
present.
• So at high blood glucose concentration, liver has a net uptake
of glucose. But it is net producer of glucose at low or normal
blood glucose concentration.

18. Hormonal Regulation of Blood glucose
There are two categories of endocrine
influences.
a) Hormone which will decrease the blood
glucose levels : Insulin
b) Hormones which will increase the blood
glucose levels: Glucagon, Epinephrine,
Cortisol and Glucocorticoids .

19. Summary of feedback mechanism for regulation
↑ blood glucose
↓
↑ insulin
↓
↑ transport of glucose into cells,
↓ gluconeogenesis, ↓ glycogenolysis
↓
↓ blood glucose
↓
↓ insulin
Regulation of Insulin Secretion

20. Insulin
Control Muscle
 Glucose uptake
 Glycogen synthesis
Liver
 Glucose uptake
 Glycogen synthesis
 Fatty acid synthesis
 Glucose synthesis
Brain
No effect
Pancreas
Beta cells
Gastrointestinal
hormones
Feedback
 amino
acids
 glucose
 triglyceridesAdipose
 Glucose uptake
 Glycerol production
 Triglyceride breakdown
 Triglyceride synthesis Insulin
Most Cells
 Protein synthesis
Amino
acids
Blood
glucose

22. GLUCOGON
• Overall effects of glucogon are hyperglycemic.
• It is produced by α-cells of islet cells of pancreas in response
to hypoglycemia.
• Its action are mostly opposite to those of insulin and most
actions are on liver.
• It promotes glucose sparing by inhibiting glucose utilizing
pathways, i.e.
– ↓ glycolysis through PFK-1 by decreasing fructose-1, 6-bisphosphate.
– ↓ Citric acid cycle due to reduced PDH activity due to low insulin levels.
– ↓ Glycogenesis by inhibiting glycogen synthase through phosphorylation
• It promotes glucose production by the following:
– ↑Glycogenolysis by stimulating phosphorylase through phosphorylation.
– ↑ Gluconeogenesis by inducing pyruvate carboxylase, pyruvate carboxykinase
and glucose 6-phosphatase.

23. Glucagon
Control
Liver
 Glycogen breakdown
 Glucose synthesis
 Glucose release
Brain
No effect
Pancreas
Alpha cells
Exercise
Feedback
Adipose
 Triglyceride breakdown
 Triglyceride storage
 Blood glucose
 Fatty acids
Epinephrine
(stress)
Amino acids

24. Insulin – Anabolic and Glucagon - Catabolic
Metabolic Action Insulin Glucagon
Glycogen synthesis ↑ ↓
Glycolysis (energy release) ↑ ↓
Lipogenesis ↑ ↓
Protein synthesis ↑ ↓
Glycogenolysis ↓ ↑
Gluconeogenesis ↓ ↑
Lipolysis ↓ ↑
Ketogenesis ↓ ↑

25. Epinephrine
– The second early response hyperglycemic
hormone.
– Epinephrine causes glycogen breakdown,
gluconeogenesis, and glucose release from
the liver.
– It also stimulates glycolysis in muscle
– Lipolysis in adipose tissue,
– Decreases insulin secretion and
– Increases glucagon secretion.
Role of Epinephrine

27. Glucocorticoids Hormones
• Glucocorticoid hormones are mainly secreated
from adrenal cortex and some amount is also
synthesized in adipose tissue.
• They induce aminotransferase enzyme synthesis
leading to enhanced amino-acids catabolism.
• They also cause the induction of key enzymes of
gluconeogenesis (Fructose-1,6-biphosphatase,
pyruvate carboxylase ).
• Overall they increase the glucose level. ().

28. • These are long term hyperglycemic
hormones. Activation takes hours to
days.
• Cortisol is a steroid hormone
– Cortisol act to decrease glucose
utilization in most cells of the body
– Effects of these hormones are mediated
through the CNS.
-- It is synthesized in the adrenal cortex.
Cortisol

29. Growth hormone:
i)Decreases glucose uptake in tissues
ii)Increase liver gluconeogenesis
iii)It promotes fatty acids mobilization from
adipose tissues leading to incressed fatty acid
oxidation and ATP production
.
iv)Increased ATP and NADH inhibit glucose
utilization by cell in glycolysis .