Description
Introduction
Diabetes mellitus is a group of metabolic diseases in which an individual has
high blood sugar level because the body either does not produce insulin in
sufficient amount , or the body cells do not respond to the in sulin formed.
Polyuria (frequent urination), polydipsia (increased thirst), and polyphagia
(increased hunger) are some typical symptoms caused by high blood sugar.
Diabetes may be of the following two types:
1) Diabetes Mellitus Type 1: It is caused due to the lack of insulin, thus insulin
should be injected to treat this condition.
2) Diabetes Mellitus Type 2: It is caused due to insulin resistance by cells. It is
the most common type of diabetes and can be treated using:
i) Agents increasing insulin secretion by the pancreas,
ii) Agents increasing the sensitivity of target organs to insulin, and
iii) Agents decreasing the rate at which glucose is absorbed from the GIT.
Anti-diabetic agents are used for treating diabetes mellitus by decreasing the
blood glucose levels. Some of these drugs are administered orally and termed
oral h ypoglycaemic or oral anti -hyperglycaemic agents ; however, insulin,
exenatide, and pramlinti de are the only anti-diabetic drugs that are injected.
Different classes of anti-diabetic drugs exist, and they are selected based on the
nature of diabetes, individual’s age and situation, and other factors.
16.1.2. Insulin
Paul Langerhans (a German medical student) in 1869 studied that the pancreas
has two different groups of cells, i.e., the acimer cells that secrete digestive
enzymes, and islets (cells clustered in islands ) that serve a second function.
Banting, Macleod, Bert, and Collip isolated insulin from bovine pancreas and
used it for treating diabetes mellitus.
Insulin is a hormone produced in pancreas and permits the body to utilise sugar
(glucose) from carbohydrates in the food. Insulin restricts the blood sugar level s
from getting too high (hyperglycaemia) or too low (hypoglycaemia). Insulin
occurs as a white or almost white coloured crystalline powder. It is faintly
soluble in water; soluble in dilute solution of mineral acids and with degradation
in solutions of alkali hydroxide; and almost insoluble in alcohol, chloroform, and
ether.
Mechanism of Action
Insulin produces its action throughout specific insulin receptors present on
cell membranes. Insulin binds to these receptors with high specificity and
affinity . The resultant insulin-receptor complex enters the cell and releases
insulin.
The receptors inversely vary with the plasma insulin concentrations. When
insulin concentration is high , these receptors are down -regulated (number
reduced), whereas in the presence of low insulin concentrations, these receptors
are u p-regulated (numbers increase). This leads to reduced and increased
responsiveness to insulin, respectively.
Apart from receptor numbers, reduced affinity of these receptors for insulin may
also contribute to insulin resistance. Thus in Type II diabetes, reduction in body
weight can restore responsiven ess to endogenous insulin by up -regulation and
increased affinity for insulin by these receptors.
The insulin receptor contains an extracellular α sub-unit (recognition site) and a β
sub-unit, spanning the cell membrane, and containing tyrosine kinase that
constitutes the second messenger system , which through a complex series of
phosphorylation leads to glucose transporter protein activation and e ntry of
glucose into the cell.
Internalisation of insulin receptor units inside the cell may help action of insulin
or result in lysosomal degradation of these receptors.
16.1.2.3. Uses
Insulin has the following uses:
1) It is used for controlling diabetes mellitus (uncontrollable by diet alone) or
for treating insulin dependent diabetes mellitus.
2) It is used for regulating carbohydrate metabolism.
3) It is used for treating hyperkalemia.
4) It is used for treating severe ketoacidosis or diabetic coma.
16.1.2.4. Insulin Preparations
Some common insulin preparations are given in
The details given in the chapter can be summarised as follows:
1) Diabetes mellitus is a group of meta bolic diseases in which an individual
has high blood sugar level because the body either does not produce insulin
in sufficient amount, or the body cells do not respond to the insulin formed.
2) Anti-diabetic agents are used for treating diabetes mellitus by decreasing the
blood glucose levels.
3) Banting, Macleod, Bert, and Collip isolated insulin from bovine pancreas
and used it for treating diabetes mellitus.
4) Insulin is a hormone produced in pancreas and permits the body to utilise
sugar (glucose) from carbohydrates in the food.
5) Hypoglycaemic agents are used in the treatment of diabetes mellitus by
lowering the blood glucose levels.
6) Carbutamide was the first sulphonylurea that was clinically used for
treating the diabetes.
7) All the sulphonylureas have similar actions, i.e., they decrease blood
glucose levels in type 2 diabetes.
8) Tolbutamide belongs to the class of sulphonylureas.
9) Chlorpropamide is an oral anti -hyperglycaemic agent used for treating
NIDDM.
10) Glipizide is an oral medium -to-long a cting anti-diabetic drug belonging to
the class of sulphonylurea.
11) Glimepiride is the first III generation sulphonylurea.
12) Metformin is a biguanide antihypertensive agent.
13) Pioglitazone is used as an adjunct to diet, exercise, and other anti -diabetic
drugs to control type 2 diabetes mellitus.
14) Rosiglitazone is an anti -diabetic drug which not only acts on insulin
resistance, but also has anti -inflammatory effect; nuclear factor kappa -B
(NFκB) levels fall and inhibitor (IκB) levels increase in patients taking
rosiglitazone.
15) The sulphonylurea and meglitinide classes of oral hypoglycaemic drugs are
termed as endogenous insulin secretagogues as they induce the pancreatic
release of endogenous insulin.
16) Repaglinide is used for treating NIDDM. It is an oral anti -hyperglycaemic
drug of meglitinide class having short -acting insulin secretagogues that bind
to pancreatic β-cells for stimulating insulin release.
17) Acarbose is an inhibitor of α-glucosidase, which delays digestion and
absorption of carbohydrates in small intes tine, and thus decreases the
increase in blood-glucose concentrations after a carbohydrate load.
18) Voglibose is an α-glucosidase inhibitor.
Subject:- Medicinal chemistry 2
Semester:- Sem 5
Course:- Bachelor of pharmacy
