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

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Chapter | 3 Carbohydrate Metabolism and Its Diseases
Insulin decreases liver glucose production, output, and
glycogenolysis while increasing liver glucose utilization.
The net result is an increase in glucose uptake by the liver
with increased glucose oxidation, glycogenesis, and hypoglycemia.
This directional control is due to the action of
insulin on key enzymes of glucose metabolism.
Directional control for glucose production or utilization
is governed by coupled sets of opposing and irreversible
enzyme reactions at three control points of glucose metabolism.
These “ key enzyme ” couples are GK/G-6-Pase,
PFK/F-1-6-Pase, and PK/PEP-CK, PC. The kinases direct
metabolism toward glycolysis utilization because they
are phosphorylating enzymes and the opposing enzymes
reverse the direction so they are gluconeogenic.
The insulin sensitivity of the rate limiting GK reaction in
liver promotes glucose utilization. The opposing G-6-Pase
reaction increases during fasting or starvation, which
favors liver glucose production. In diabetes mellitus, even
though there is a hyperglycemia 8.33 mmol/l (150 mg/dl),
G-6-Pase is increased. Increases in the other key enzymes
of gluconeogenesis, F-1-6-Pase, PEP-CK, and PC, are also
observed in diabetes. Increases in activity of these gluconeogenic
enzymes in insulin deficiency direct metabolic
pathways toward excessive production of glucose by the
diabetic liver.
The amelioration of diabetes in an experimental animal
by hypophysectomy (Houssay animal) is well established.
The pituitary factor, which opposes the action of insulin,
is growth hormone. The glucocorticoids increase gluconeogenesis
and intracellular G-6-P and, by their insulin
opposing effect, increase free glucose. An increase also
results from the glycogenolytic action of epinephrine and
glucagon, and the equilibrium is shifted to favor of glucose
production. Therefore, it is the balance of hormones
that directly (insulin) or indirectly (epinephrine, growth
hormone, glucagon, cortisol) affects glucose metabolism,
which sets the “ steady-state blood glucose ” at which the
liver neither uses glucose or produces glucose.
D . Glucose Tolerance
The regulatory events that occur in response to changes
in blood glucose concentration are best summarized by a
description of the events following ingestion of a test dose
of glucose. When administered orally to a normal animal,
a typical change in blood glucose concentration with time
is observed as shown in Figure 3-12 . During the absorptive
phase, phase I, the rate of entry of glucose into the circulation
exceeds that of removal and the blood glucose rises.
As the blood glucose rises, hepatic glucose output is inhibited
and the release of insulin from the pancreas is stimulated
by the rising blood glucose. This release of insulin is
also influenced by the insulin releasing effect of the GI hormones:
secretin, cholecystokinin-pancreozymin (CCK-PZ),
FIGURE 3-12 Oral glucose tolerance in the dog; I, II, and III are phases
of the curve.
gastrin, and by pancreatic glucagon. In 30 to 60 min, the
peak level of blood glucose is reached, after which it
begins to fall. During this phase of falling blood glucose,
phase II, the rates of removal now exceed those of entry
and the regulatory mechanisms directed toward removal of
glucose are operating maximally. At the same time, hepatic
glucose output decreases and the blood glucose falls rapidly.
When the blood glucose reaches its baseline level, it
continues to fall below the original level for a short time
and then returns to its baseline level. This hypoglycemic
phase, phase III, is due to the inertia of the regulatory
mechanisms because, in general, the higher the glycemia,
the greater the subsequent hypoglycemia. Clinically, this
postinsulin hypoglycemia can be marked if there is a defect
in the secretion of glucagon.
VIII . METHODOLOGY
A large number of tests have been devised to evaluate the
status of the carbohydrate economy of animals but the principal
focus continues to lie with the determination of blood
glucose levels. The hexokinase (HK), glucose dehdrogenase
(GD), and the glucose oxidase (GO) methods are currently
the most widely used methods for blood glucose and
are used in manual, automated, and in point-of-care testing
modules.
A . Blood Glucose
1 . Methods
Three glucose-specific enzyme methods are in use: the GO,
HK, and the GD methods. The GO method is coupled with