Synthesis, Storage and Secretion of Insulin
The information regarding synthesis, storage and
secretion of Insulin was given by D.F. Steiner and his colleagues. The origin
goal was to determine regarding the synthesis of A and B chains of insulin and
the construction of disulfide cross linkages. The incubation of radioactive
substances such as lucine and phenylalanine is done with islet tissues of rat
pancreas or human pancreatic tumors and tumors of this type produce excessively
large amount of insulin. Production of two radioactive proteins occurs from the
pancreatic tumor and is capable of combining with a specific antibody to pure
insulin. One was established to be insulin itself. The other one is closely
related resembled to insulin itself because it has reacted to anti-insulin
antibody and is substantially having larger molecular weight than insulin.
Treatment of the second product with trypsin and carboxypeptidase causes
cleavage of a number of peptide bonds and the formation of a compound that was
proved to be identical with native insulin.
Chemical
and enzymatic degradation studies on pancreas showed that large insulin like
molecule formed by the pancreas. The molecule is known as proinsulin and it
consists of a single polypeptide chain having from 81 to 86 residues, depending
on the origin of the species. Both A and B chains are present in proinsulin.
The A chain constitutes the carboxyl-terminal end of the proinsulin chain and B
chain the amino-terminal end. Between the A and B chains is the connecting C
chain. Two pairs of basic amino acids separate the A and B chains from the C
chains.
Proinsulin,
which has only a small amount of insulin like activity itself, is the
biosynthetic precursor of insulin. The transformation of proinsulin into
insulin is apparently accomplished by the action of peptidases in the islet
tissue. The conversion of proinsulin to insulin is another example of the
pattern of synthesis and activation of a number of proteins whose biological
function is largely extracellular.
Insulin
is first made on the ribosomes in the form of proinsulin, which is translocated
via the cisternae of the endoplasmic reticulum to the Golgi apparatus. The proinsulin
is cleaved to form insulin and C-peptide, which are packaged in Golgi vesicles,
where the insulin and C-peptide crystallize with Zn2+ in an ordered
array. Ultimately, on receipt of certain signals triggered by an increase in
the blood glucose level, the contents of these vesicles are released by exocytosis
through the plasma membrane into the blood. Ca2+ plays an important
role in insulin release.
The normal
human pancreas contains about 10 mg of insulin, but the amount secreted into
the blood daily is only about 1 to 2 mg. Free C-peptide and a small amount of
proinsulin also circulate in the blood; they are apparently released together
with insulin. Depending on the glucose concentration and certain other factors,
the release of insulin from the pancreas occurs. When the blood glucose increases
significantly above its normal level of about 80-90 mg per 100 ml, after a
meal, the contents of the secretion vesicles closest to the plasma membrane of
the β cells are ejected into the blood. The insulin concentration then declines
to the normal level in an hour or two after a meal. The half-life of insulin
molecules in the blood is only about 3 to 4 min; the release of insulin from
the pancreas therefore is very responsive to fluctuations in the blood glucose concentration.
The release of insulin is also stimulated by increased level of certain amino
acids and by specific factors secreted by the stomach and intestine.
Source:- Biochemistry Second Edition, The Molecular Basis of Cell Structure and Function, Albert L. Lehninger, The Johns Hopkins University School of Medicine, Page number 417-420.
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