Insulin, Glucose homeostasis & Diabetes mellitus:Biochemistry:U.Satayanarayan

ll iabetes mellitus is the third leading cause
lJ of death (after heart disease and cancer) in
many developed countries. lt affects about 2 to
3% of the general population. The complications
of diabetes affect the eye, kidney and nervous
system. Diabetes is a major cause of blindness,
renal failure, amputation, heart attacks and
stroke. (The term diabetes, whenever used, refers
to diabetes mellitus. lt should, however, be
noted that diabetes insipidus is another
disorder characterized by large volumes of
urine excretion due to antidiuretic hormone
deficiency).
Diabetes mellitus is a clinical condition
characterized by increased blood glucose level
(hyperglycemia) due to insufficient or inefficient
(incompetent) insulin. ln other words, insulin is
either not produced in sufficient quantity or
inefficient in its action on the target tissues. As a
consequence, the blood glucose level is elevated
which spills over into urine in diabetes mellitus
(Creek : diabetes-a siphon or running through;
mellitus-sweet).
An important feature of diabetes is that the
body cells are starved of glucose despite
its very high concentration around i.e. scarcity in
plenty. For a comprehensive understanding of
diabetes, the relevant hormones, namely insulin
and glucagon, homeostasis of blood glucose,
besides the biochemical aspects of diabetes, are
discussed in this chaoter.
lnsufin is a polypeptide hormone produced
by the B-cells of islets of Langerhans of
pancreas. lt has profound influence on the
metabolism of carbohydrate, fat and protein.
Insulin is considered as anabolic hormone, as it
promotes the synthesis of glycogen,
triacylglycerols and proteins. This hormone has
been implicated in the development of diabetes
mellitus.
Insulin occupies a special place in the history
of biochemistry as well as medicine. Insulin was
the first hormone to be isolated, purified and synthesized.Clucagon, secreted by a-cells of the pancreas,
opposes the actions of insulin. lt is a polypeptide
hormone composed of 29 amino acids (mol. wt.
3,500) in a single chain. Clucagon is actually
synthesized as proglucagon (mol. wt. 9,000)
which on sequential degradation releases active
glucagon. Unlike insulin, the amino acid
sequence of glucagon is the same in all
mammalian species (so far studied). Clucagon has
a short half-life in plasma i.e. about 5 minutes.
f, ++qu[et i tr ! af q! Nle;t g€'re li€rcrr!.f idi*l
The secretion of glucagon is stimulated by
Iow blood glucose concentration, amino acids
derived from dietary protein and low levels of
epinephrine. Increased blood glucose level
markedly inhibits glucagon secretion.
ftiletahe;iit: ei'fe:lts oi qgir.l*;: r';nn
Clucagon influences carbohydrate, lipid and
protein metabolisms. In general, the effects of
this hormone oppose that of insulin.
1. Effects on carbohydrate metabolism :
Glucagon is the most potent hormone that
enhances the blood glucose level (hyperglycemic).
Primarily, glucagon acts on liver to cause
increased synthesis of glucose (gluconeogenesis)
and enhanced degradation of glycogen
(glycogenolysis). The actions of glucagon are
mediated through cyclic AMP (Chapter t3).
2. Effects on lipid metabolism : Clucagon
promotes fatty acid oxidation resulting in
energy production and ketone body synthesis
(ketogenesis).
3. Effects on protein metabolism : Glucagon
increases the amino acid uptake by liver which,
in turn, promotes gluconeogenesis. Thus,
glucagon lowers plasma amino acids.
Meehanisrn of ;.icti*"rri #[ g{e.E$fil{g}f,
Clucagon binds to the specific receptors on
the plasma membrane and acts through the
mediation of cyclic AMP, the second messenger.
The details are given elsewhere Diabetes mellitus is a metabolic dr'sease, more
appropriately adisorder of fuel metabolism. lt is
mainly characterized by hyperglycemia that
leads to several long term complications.
Diabetes mellitus is broadly divided into 2
groups, IDDM & NIDDM.