B.
SC honours 6th semester Project Work
2021
Roll-2115120 No-180187
Registration No- 017477 of 2018-2019
Subject -Chemistry
Paper–CHEMHTDSE-4(Theory)
College name -Kanchrapara college
Student name -Dhruba Jyoti Kirtania
Topic- Insulin
[These pictures are collected from Google ]
Insulin
Introduction :
Insulin is a peptide hormone that is synthesized and secreted by beta cells
in the Langerhans islets of the [Link] regulates carbohydrate, fat,
and protein metabolism by providing glucose in the blood to pass to
fat,liver and skeletal muscle cells. A metabolic disease called diabetes
occurs as a result of inadequate insulin activity in the body or the
deterioration in insulin secretion in beta cells. Globally diabetes is a
fast-growing chronic illness which increases the risk of renal & cardiac
diseases, and also invites viral ,bacterial or fungal infections in the
human body . Insulin administration via injection is the most effective
way to treat this illness.
General discussion :
History of insulin :- Insulin is derived from the Latin word insula,
meaning island. In 1869, Paul Langerhans' found an unspecified cell
cluster in the pancreas other than exocrine [Link] 1921, Canadian
orthopedic doctor Frederick G . Banting and his assistant Charles Best
Identified insulin hormone. The molecular structure of insulin was
discovered in 1955 by Frederick Sanger .
Structure of insulin :-Insulin (M .W 6000Da) has two
polypeptide chains, A and B chain containing 21 and 30 amino acid
residues, [Link] two chains are interconnected by SS
(CysA7-CysB7 and
CysA20-CysA19)
with a disulfide bond,
and an additional SS
bond connects CysA6
and CysA11 in chain
A . The formation of
[this photo is collected from Google ]dimer ,tetramer, hexamer or
higher grade aggregates can be observed. It varies depending on insulin
concentration, pH , solution composition and metal ion concentration.
Insulin
This also affects the charge
and solubility of the insulin
[Link] human
insulin molecules are only
present in very low
concentrations (<1x10¯⁹
M ) and dimer is formed at
a concentration of 1x10-6
M . In the presence of zinc
or other metal ions; three
human insulin dimers
{This photo is collected from Google } easily combined with hexamer.
2Zn hexameric insulin is collected in the coordination of two zinc ions and
has a structure similar to the natural storage types of the peptide in
pancreatic beta [Link] structure also prevents the formation of higher
grade aggregates.
insulin Receptors : The insulin receptor is a member of the
transmembrane signal proteins of the tyrosine kinase family and is
synthesized as a single polypeptide. The formed polypeptide is
glycosylated and divided into alpha-beta subunits, and a tetramer is
formed, which is bound by disulfide bonds again. The hydrophobic part of
each subunit is located within
the plasma membrane. Alpha
subunit contains the insulin
binding site. The cytosolic
part of the beta subunit is a
tyrosine kinase and is
activated by insulin. Binding
of insulin to alpha subunits
of the receptor causes
positional changes .These
changes are transmitted to
Insulin
beta subunits, ( photo collected from Google ) and the
tyrosine unit in these
structures causes autophosphorylation. Consequently, insulin-receptor
substrates (IRS-1 and IRS-2) activate phosphorylated
phosphatidylinositol-3 kinase (PI3K) and mitogen activated protein
kinase pathways. Eventually, insulin acts on the target tissues. In
combination with the receptor, the complex activates the 'second
messenger', which in turn causes release of the third messenger, Ca2+
membrane effect increasing glucose uptake as well as its utilisation,
especially by muscle and adipose ions.
Future on oral insulin :-The physiological barriers to absorption of
oral insulin,its low bioavailability and low biopotency, and the high
inter-patient variability, are challenges that researchers need to
overcome before oral insulin can be considered as suitable candidate for
treatment of diabetes [Link] reports, including
proof -of -concept studies,and early clinical studies, however, are reason
for opti-mism that oral insulin will soon become a reality.
Importance : Without insulin, the blood glucose builds up in the
blood and the cells are starved of their energy source. Some of the
symptoms that may occur include fatigue, constant infections, blurred eye
sight, numbness, tingling in the hands or legs, increased thirst, and
slowed healing of bruises or cuts. The cells will begin to use fat, the
energy source stored for emergencies. When this happens for too long a
time the body produces ketones, chemicals produced by the liver. Ketones
can poison and kill cells if they build up in the body over an extended
period of time. This can lead to serious illness and coma .
References : 1.'CLINICAL PHARMACOLOGY ' BY D. R.
Laurence and [Link] .
[Link] et al.: Oral Insulin. Diabetology & Metabolic Syndrome
2010 2:66.
Insulin
[Link] LIVINGSTON POCKET MEDICAL
DICTIONARY (LOIS OKES) , NANCY ROPER .