Clinical Biochemistry of Domestic Animals (Sixth Edition) - UMK ...

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Chapter | 3 Carbohydrate Metabolism and Its Diseases
Insulin and C-peptide are released into the circulation
in equimolar amounts but C-peptide’s circulatory concentration
is higher than that of insulin because of its slower
clearance half-time of 20 min as compared to 5 to 10 min
for insulin. C-peptide is primarily degraded by the kidney
and a portion is excreted in the urine ( Duckworth and
Kitabchi, 1981 ).
In the pancreatic cells, as the insulin moiety is cleaved
from the proinsulin, it crystallizes with zinc for storage
in the β -cell granules. The dense central inclusions
of these insulin secretory granules consist mainly of crystalline
insulin. Insulin release is stimulated by glucose,
amino acids, hormones (glucagon, gastrin, secretin, pancreozymin),
and drugs (sulfonyl ureas, isoproterenol).
B 1
A 1
S
S
S
C-PEPTIDE
S
INSULIN
B-CHAIN
A-CHAIN
S
S
A 21
B 30
FIGURE 3-11 Insulin and proinsulin. Proinsulin is the coiled polypeptide.
When the connecting C-peptide (open circle) is removed, the insulin
molecule (solid circle) is released.
Insulin release is inhibited by hypoglycemia, somatostatin,
and many drugs, such as dilantin and phenothiazines .
The liver is the primary site of insulin degradation, and
the kidney is a secondary site. The half-life of insulin in the
circulation is between 5 and 10 min ( Steiner, 1977 ).
The A chain of insulin consists of 21 amino acids and
the B chain of 30 amino acid residues ( Fig. 3-11 ). The m.w.
of the insulin monomer is 6000 daltons and is the smallest
unit possessing biological activity. Under physiological conditions,
4 molecules of insulin are linked together to form
a tetramer, the active molecule. Insulin obtained from various
species differs in amino acid composition in Chain A
or Chain B or both ( Table 3-4 ). Differences occur within
species also as rats and mice ( Markussen, 1971 ) have two
nonallelic insulins. These structural differences among the
various species of animals are not located at critical sites,
however, because they do not affect their biological activity.
They do, however, affect their immunological behavior.
The amount of insulin stored in the pancreata of various
species also differs. The dog stores about 3.3 units per gram
of pancreas, which amounts to about 75 I.U. in a 10-kg
dog. This amount, if suddenly released, would be fatal.
Insulin release is affected by glucose, mannose, leucine,
other amino acids, ketone bodies, and fatty acids. This release
is mediated by glucagon, a hormone, which increases cAMP
and potentiates the insulin response. The sulfonylureas
are effective as pharmacological agents to release insulin,
the basis for their therapeutic use.
TABLE 3-4 Species Variation in Amino Acid Sequences of Insulin a
Position a
Species A Chain B Chain
A-4 A-8 A-9 A-10 B-3 B-29 B-30
Human Glu Thr Ser Ileu Asp Lys Thr
Monkey Glu Thr Ser Ileu Asp Lys Thr
Dog Glu Thr Ser Ileu Asp Lys Ala
Pig Glu Thr Ser Ileu Asp Lys Ala
Sperm Whale Glu Thr Ser Ileu Asp Lys Ala
Rabbit Glu Thr Ser Ileu Asp Lys Ser
Horse Glu Thr Gly Ileu Asp Lys Ala
Cow Glu Ala Ser Val Asp Lys Ala
Sheep Glu Ala Gly Val Asp Lys Ala
Sei Whale Glu Ala Ser Thr Asp Lys Ala
Rat 1 Asp Thr Ser Ileu Lys Lys Ser
Rat 2 Asp Thr Ser Ileu Lys Met Ser
From Renold and Cahill (1966) and Naithani et al. (1984).
a
These are the sites of variation on the A chains and the B chains. Ala alanine; Asp aspartic acid; Glu glutamic acid; Ileu isoleucine;
Met methionine; Ser serine; Thr threonine.