2. Diabetes mellitus
• Diabetes mellitus is a chronic metabolic
disease caused by insulin deficiency and
insulin resistance.
• The result is disordered utilization and
storage of the carbohydrates, proteins and
fats and reduced production of energy.
3. Function of α, β, δ cells of pancreas
• The different cells of pancreas & their functions:
1. α-cells produce glucagon
• It promotes conversion of glycogen into glucose,
when required to meet the energy needs of the
body.
2. β-cells produce insulin
• It removes the excess glucose from blood and
converts it into glycogen.
3. δ-cells produce somatostatin
• It maintains a proper proportion of insulin and
glucagon.
4. Hyperglycemia
With onset of diabetes , insulin is not produced or it is insufficient.
Insulin controls the metabolism of carbohydrates, lipids and proteins.
In absence of insulin glucose is not metabolised at normal rate. Hence, there is an increase in
concentration of glucose in blood causing a condition called hyperglycemia.
Thus the blood glucose levels rise above the normal levels which is 60-90 mg/100 ml.
5.
6. Symptoms of Diabetes mellitus
Polyuria
Polydipsia
Glucosuria
Ketonuria
Muscular weakness & weight loss
Degeneration of the walls of fine capillaries. (condition : Diabetes foot)
Glaucoma may cause blindness
7. Types of Diabetes mellitus
Types –I or
Juvenile
onset
diabetes
Types –II or
Maturity
onset
diabetes
Types –III
Types –IV
or
Gestational
diabetes
mellitus
8. Types of Hypoglycemic Agents
Insulin
therapy
Insulin is a hormone consisting of two polypeptide chains having 21 and 30
α-amino acids, which are held together by disulphide (-S-S-) linkage.
Insulin is used to control hyperglycemia in diabetes mellitus and it is called
hypoglycemic agent. Insulin dose has to be given by injection through a
subcutaneous route.
It cannot be given by oral route as it is a protein and hence gets digested by
enzymes in the gastrointestinal tract. Insulin which is injected directly enters
the systemic circulation and hence it is more effective than other oral
hypoglycemic agents.
hoto by Unknown Author is licensed under CC BY-SA
9. Dosage forms of insulin therapy
Type Time for
onset of
action
Duration of
action
Dosage form
(i) Rapid acting
(ii)Intermediate
acting
(iii) Long acting
<1 hr
1-4 hrs
4-6hrs
5-7 hrs
18-24 hrs
24-36 hrs
Insulin-zinc
suspension
Globulin-zinc insulin
suspension
Protamine-zinc
10. Drawbacks of insulin therapy
The treatment with insulin may cause cardiovascular & renal problems.
The improper insulin administration may affect vision ( may cause cataract &
even blindness )
Insulin being a protein, may cause allergic & hypersensitivity reactions
Benign tumors may develop (lipodystrophy) at the site of injection which
slows down the absorption of insulin.
Bovine and porcine insulin are antigenic (i.e. they generate insulin antibodies).
These antibodies binds insulin which decreases its effectiveness & leads to insulin
resistance, especially when insulin used is not highly purified
11. Oral Hypoglycemic Agents
1. Glybenclamide (Glyburide) (Sulphonyl
Ureas)
• It is highly potent oral hypoglycemic agent
• Use:
i. It is mainly used in the treatment of type
Il Or maturity onset diabetes.
ii. It cannot be used in case of type 1
diabetes.
• Side effects:
• abdominal complaints
12. Metformin (Biguanide)
• It belongs to the biguanide class of compounds.
• Use:
• Metformin is mainly used in treatment of type 1
diabetes or juvenile onset diabetes.
• It can also be used along with sulphonyl ureas, e.g.,
Glybenclamide.
• Side effects:
• Mainly abdominal discomfort and muscular
weakness.
13. Dapagliflozin (Pyranose)
• Use: It is a drug of gliflozin class used in the treatment of type-Il
diabetes.
• Side effects: Heavy glycosuria, rapid weight loss and tiredness.
14. Pioglitazone (Glitazones)
• It belongs to the Thiazolidinediones or TZDs class
of compounds.
• Use: It is used to control the blood sugar levels in
patients with type Il diabetes.
• Pioglitazone is used either alone or in combination
with Metformin or Glibenclamide.
• Side effects:
• Anaemia, back pain, blurred vision, fluid retention,
hypoglycemia, extreme tiredness.
15. SYNTHESIS OF PIOGLITAZONE (GLITAZONES)
1. 2-(5-Ethylpyridin-2-yl) ethanol is condensed with 4-fluorobenzo nitrile
in presence of NaH to give 4-[2-(5-ethyl-2-pyridyl) ethoxy]
benzonitrile (II), which on reduction yields the corresponding aldehyde
(III).
2. The aldehyde (III) on reaction with thiazolidine -2,4-dione in basic
medium yeilds (iv), which on hydrolysis yields pioglitazone
16. Synthesis of Pioglitazone (Glitazones)
CH3
N OH
2-(5-Ethylpyridin-2-yl)
ethanol
NaH
CN
F
CH3
N O
CN
(II)
STEP-1
Ra -Ni, HCOOH
CH3
N O
CHO
(III)