Chapter 13- Regulation of glycemia

Glycemia: Concentration of glucose in the blood

Glucose is the first source of energy for most cells. Despite the important
variations of glycemia (after a meal or a long fast), glycemia fluctuates around a
constant value (0.8 – 1.2 g/l) due to the presence of a system of regulation.

Document 1: Glycemia, a biological constant.

1- Regulation of glycemia:
The average value of glycemia is: 0.8 g/l = 80 mg/dl = 4.4 mmol/l
Variations in the level of glycemia can be detected:
• After a meal: increase in glycemia or hyperglycemia is observed (> 1.2 g/l)
• During muscular work or fasting: decrease in glycemia or hypoglycemia (< 0.8
g/l)

- the body is provided with a regulating system which brings glycemia to its
normal value.

- body organs contain reserves of glucose.

Document 2: The liver, an effector organ in the regulation of glycemia.

- The liver stores glucose when it is in
excess, while it releases it in the case of
deficiency in order to maintain glycemia
constant.

- the liver can release glucose in the blood.

Functions of the liver:

- The sugar that is carried away while
washing, which is very soluble in water.
This sugar is glucose
- Another substance which is slightly soluble in water, stored in the liver and
which transforms into sugar. This substance is glycogen.
Glycogen (C6H10O5)n is formed from the combination of glucose molecules

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 The reactions that take place in the liver, muscles, adipose tissue:
Hyperglycemia or after a meal

Liver, muscles
Glucose glycogen Glycogenesis

Glucose lipids lipogenesis.

Adipose tissue
Hypoglycemia or after a fast
Liver
Glycogenolysis : Glycogen glucose

lipolysis Liver
Neoglucogenesis: Lipids fatty acids + glycerol glucose
(Adipose tissue)

Amino acids glucose

(muscles) Liver

Neoglucogenesis: Production of glucose from sources other than glycogen.

Remarks:
The liver is the only organ capable of releasing glucose directly since it contains an
enzyme called glucose 6 phosphatase. This enzyme can remove the phosphate from
the glucose resulting from the hydrolysis of glycogen. As a result. Glucose, void of
phosphate, can leave the liver toward blood.
The muscles: The enzyme G6Pase is absent in the muscles. That’s why the muscles
cannot release glucose directly in the blood. Instead, it releases amino acids that
pass into the liver to be transformed there into glucose (neoglucogenesis).
The adipose tissue: it cannot release glucose directly. Instead, lipids are
hydrolyzed into fatty acids and glycerol, the glycerol is transformed in the liver
into glucose (neoglucogenesis).

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Conditions required for the functioning of the liver, muscles, adipose tissue in
the regulation of glycemia:
Liver Muscles Adipose tissue
Storage It stores glucose It stores glucose It stores glucose
(when glycemia in the form of in the form of in the form of
increases) glycogen glycogen lipids
Release It releases It provides the It provides the
(when glycemia glucose from amino acids that glycerol that the
decreases) amino acids and the liver liver transforms
glycerol and transforms into into glucose
releases it in the glucose
blood
Direct release It releases It cannot release It cannot release
(when glycemia glucose directly glucose directly glucose directly
decreases) by the hydrolysis from glycogen
of glycogen due due to the
to an enzyme G6 absence of
Pase G6Pase

Document 3- The pancreas and glycemia

1- The pancreas: a mixed gland

The pancreas is an organ located under the stomach. It is a mixed gland since it is
exocrine and endocrine.
Exocrine function of the pancreas: the exocrine pancreas is formed of exocrine
cells called acini that present an excretory duct through which they secrete the
pancreatic juice (it contains enzymes important for digestion).
Endocrine function of the pancreas: the endocrine pancreas is formed of clusters
of cells called Islets of Langerhans void of excretory ducts and rich with blood
vessels. These Islets contain two types of cells:
• α cells that secrete glucagon, a hyperglycemic hormone.
• β cells that secrete insulin, a hypoglycemic hormone.

2- Diabetes
Diabetes is a disorder characterized by a permanent hyperglycemia greater than
1.2 g/l.
Glycosuria: appearance of glucose in the urine
Polyuria: excess of elimination of urine.

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the pancreas has two roles: a digestive role and another hypoglycemic role ensured
by a substance (insulin) produced by the Islets of langerhans and secreted in the
blood.

Document 4: Hypoglycemic system

The pancreas secretes in the blood a hormone called insulin having a hypoglycemic
effect. It acts on the liver, its target organ, which stores glucose and thus
decreases glycemia.

Chemical nature of insulin:

Insulin is a protein formed of 51 amino acids that are divided into two chains A and
B. it is produced by the β cells of the Islet of Langerhans.
Insulin is never administered orally since it can be digested by the proteases of
the digestive system so it is always administered through blood.

hyperglycemia stimulates the secretion of insulin.

Role of insulin:
insulin is a hypoglycemic hormone. It acts on hepatic cells and muscular cells to
store glucose in the form of glycogen.

4- Mode of action of insulin

Hormone and target cell: Every hormone acts on specific cells called target cells.
A target cell is the cell that modifies its behaviour under the action of a hormone.
Target cells present receptors (membranous or intracellular) specific for this
hormone. When the hormone fixes on its receptor, the complex Hormone-Receptor
triggers a physiological response that corresponds to the inhibition or the
activation of the target cell.

β cells of the pancreas release by exocytosis the hormone insulin in the blood.
Insulin fixes on its specific membranous receptor of the target body cell and
activates a messenger inside the target cell. This messenger increases the
permeability of the target cell to glucose and allows the storage of glucose in the
form of glycogen. As a result, the level of glycemia decreases.

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Document 5: Hyperglycemic system
The pancreas secretes in the blood, in addition to insulin, a hormone called glucagon
having a hyperglycemic effect.

Chemical nature of Glucagon:

Glucagon is a polypeptide made up of 29 amino acids and it is secreted by the α
cells of the Islets of Langerhans.

glucagon is secreted when glucose level is low

Role of glucagon:
glucagon is a hyperglycemic hormone that acts on hepatic cells in order to increase
the level of blood glucose.

4- Other hyperglycemic hormones:

All hyperglycemic hormones work like glucagon: they release the glucose that is
stored and reduce its usage by the cells.
Example:
- Adrenalin: it is secreted by the adrenal cortex gland. It activates
glycogenolysis and neoglucogenesis.
- Cortisol: it is secreted by the adrenal medulla gland. It reduced the use of
glucose by cells and activates lipolysis.
- Growth hormone (GH): it is secreted by the pituitary gland. It activates
glycogenolysis and neoglucogenesis and inhibits the use of glucose by muscle
cells.
- Thyroxine: it is secreted by the thyroid. It increases the intestinal
absorption of glucose.

5- Types of diabetes:
They are divided into two groups:
- IDD or insulin dependant diabetes: this type can be treated by insulin
injections since it is due to either a low number or absence of β cells
(juvenile diabetes) or it is due to the production of abnormal insulin
(mutated insulin gene).
- NIDD or non –insulin-dependant diabetes : this type cannot be treated
with insulin since it is due to the presence of very few insulin receptors or

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 even the absence of insulin receptors. This is the case of maturity-onset
diabetes.

Document 6: Regulation of glycemia by feedback control.

Glycemia is controlled by the glycemic value itself, that’s why the regulation of
glycemia is called an autoregulation. This autoregulation is ensured by a negative
feedback control (retrocontrol).

1- Autoregulation of Glycemia by negative feedback:

Hyperglycemia stimulates β cells that secrete insulin and inhibits α cells that
secrete glucagon, thus leading to a hypoglycemia.
On the other hand, hypoglycemia stimulates α cells that secrete glucagon and
inhibits β cells that secrete insulin thus leading to a hyperglycemia.
In both cases, the level of glycemia is controlled.

Diagram summarizing the autoregulation by feedback control of glycemia:

Increase in blood glucose Decrease in blood

Concentration Glucose concentration

Increase In Decrease in Decrease in Increase in

insulin secretion glucagon secretion insulin secretion glucagon secretion

Role of the nervous system and adrenal medulla in the regulation of glycemia:
(Doc.b)

The hypothalamus is a small organ situated in the brain, which contains cells that
are sensitive to stress and glucosensitive (sensitive to glucose).
When there is stress or when there is hypoglycemia, the hypothalamus sends a
nervous message through the sympathetic nerves to the adrenal medulla gland
which secretes adrenalin. This hyperglycemic hormone stimulates lipolysis in the
adipose tissue and glycogenolysis in the liver.

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Lipolysis leads to the release of fatty acids and glycerol which transforms later
into glucose at the level of the liver. Moreover, the hepatic glycogen is hydrolyzed
into glucose (glycogenolysis). As a result, a hyperglycemia is obtained.

Functioning diagram of the regulation system of glycemia

Feedback control

Effectors

Regulation
Islets of Insulin of
Langerhans Glucagon Liver glycemia
Muscles
Adipose
tissue
Adrenal medulla Adrenalin

Nervous pathway Hypothalamus

hypoglycemia
Stress