MEDICINAL CHEMISTRY

(ii) Non-Insulin dependent diabetes mellitus (NIDDM) : This type has more definite
genetic and hereditary characteristics. This disease type announces its presence quite
late. More often this is a disease of affluent and old aged people and is more common in
women than in men. The patient retains a considerable number of functioning cells
making insulin deficiency less severe. However the population of α-cells is increased
without major changes in D or PP cells. Ketosis does not occur and wasting is not a
common feature. This indicates that this type may not need any treatment except a strict
dietary restriction.
The Hypoglycemic agents are classified into 2 categories:-
(1)Insulin & Insulin preparations- used parentally only.
Insulin synthesized by (-cells of the islets of langerhans of the pancreas in the form of
proinsulin. It is a single peptide chain. Human proinsulin consists of 76 amino acids
residues & on its conversion to human insulin four basic amino acids & the remaining
peptide chain called c-peptide are removed by proteolysis.
Insulin consists of two peptide chain A & B which are converted by disulphide bonds.
Chain A- has 21 Amino acid & one intra chain Disulphide bond. And Chain B- has 30
Amino acid.
Bovine insulin has 2 Amino acid in the middle of the chain A and one at the end of chain
B that are different from human insulin. Bovine insulin differs only by the presence of
alanine as the last amino acid in the chain B, where the human insulin has threonine.
Insulin occurs as haxamer containing two zinc atoms and in the system (in blood)
dissociates into monomers is the most likely biologically active form of the insulin.
Semi synthetic human insulin is produced by the enzymatic modifications of insulin
obtained from the procaine e pancreas.
The duration of actions of insulin may be prolonged- Firstly by forming a complex of
insulin with a protein from which it is slowly released. e.g. Protamine zinc insulin,
Isophane insulin, Globin zinc insulin. Secondly by modification of the particle size, e.g.
Insulin zinc suspension.
Insulin Preparations
(a) Short - acting Insulin preparations: As the plasma half-life of intravenously
injected insulin is not enough to meet the requirements, one has to search for such insulin
preparations, having quick onset and prolong duration of action. Presently, available
insulin preparations differ only with respect to onset and duration of action. First
clinically used form was amorphous insulin which was highly soluble in body fluids.
This leads to its rapid excretion and hence it was to be replaced by other insulin
preparations. In early 1940's came 'Regular insulin' which is a buffered solution of
crystalline zinc insulin. Duration of action of this preparation still needs improvement.
Chemically pure zinc insulin has physiologic action essentially identical to that of regular