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

VII. Blood Glucose and Its Regulation
61
Somatostatin has broad inhibitory effects on the release of
many hormones, including growth hormone, glucagon, and
insulin. Therefore, it has a modulating effect on the actions
of these two hormones. Administration of somatostatin
blocks the secretion of glucagon; in this way, somatostatin
exacerbates an insulin-induced hypoglycemia.
VII . BLOOD GLUCOSE AND ITS
REGULATION
A . General
The blood glucose concentration depends on a wide variety
of factors and its concentration at any time is the net
result of an equilibrium between the rates of entry and
of removal of glucose in the circulation. As such, all the
factors that exert influence on entry or removal become
important in the regulation of blood glucose concentration.
Furthermore, when the renal reabsorptive capacity for glucose
is exceeded (renal threshold), urinary loss of glucose
becomes an additional factor influencing the maintenance
of the blood glucose concentration. The blood glucose levels
at which this occurs vary between species and are listed
in Table 3-6 .
B . Glucose Supply and Removal
Glucose is supplied by intestinal absorption of dietary glucose
or by hepatic glucose production from its precursors,
for example, carbohydrates (glycogen, fructose, galactose)
and amino acids (gluconeogenesis). The dietary sources
of supply of carbohydrates are especially variable among
the various species. The absorptive process varies with the
degree of systemic hormonal activity (e.g., thyroid) and gastrointestinal
hormone activity (e.g., secretin). All conditions
affecting gastrointestinal digestive processes (e.g., gastrointestinal
acidity, digestive enzymes, disease) substantially
affect absorption of glucose. Hence, it is important to evaluate
the blood glucose in virtually all diseases.
TABLE 3-6 Renal Thresholds for Glucose in
Domestic Animals
Species
Reference
(mg/dl) (mmol/l)
Dog 180–220 10.0–12.2 Shannon et al . (1941)
Horse 180–200 10.0–11.1 Stewart and Holman
(1940)
Cow 98–102 5.4–5.7 Bell and Jones (1945)
Sheep 160–200 8.9–11.1 McCandless et al . (1948)
Goat 70–130 3.9–7.2 Cutler (1934)
In the postabsorptive state, hepatic production is the
major source of supply for maintaining blood glucose. The
hormones epinephrine and glucagon promote the release of
glucose from glycogen as described in Section IV.C.2. The
glucocorticoids promote gluconeogenesis and oppose the
hypoglycemic action of insulin.
Removal of glucose is governed by a variety of factors,
most of which ultimately relate to the rate of utilization
of glucose. All tissues constantly utilize glucose either for
energy purposes or for conversion into other products (glycogen,
pentoses, lipids, amino acids). Therefore, an outflow
of glucose from the circulation, which is governed by the
rate of utilization of glucose by a tissue, occurs at all times.
The level of blood glucose itself partially governs the rate
of utilization and therefore, in a sense, is autoregulatory.
At high levels, the rate of glucose uptake by tissues such
as muscle and liver increases because of mass action. The
presence of insulin increases the rate of glucose utilization,
either by increased transport via GLUT-4 (muscle, fat) or
increased phosphorylation (liver). The action of insulin
is opposed by the diabetogenic factors, growth hormone,
glucagon, cortisol, and epinephrine.
The liver occupies a central position in the regulatory
mechanism of blood glucose concentration because it supplies
as well as removes glucose from the system. The
major direction of liver glucose metabolism is directed
toward supplying rather than using glucose. When liver
takes up glucose, 25% is oxidized to lactate or CO 2 and the
remainder forms glycogen. This glycogen is the source of
the glucose supplied by the liver to the system during the
better part of a day. Muscle, on the other hand, does not
contain G-6-Pase, so it cannot provide free glucose and is
therefore primarily a glucose-utilizing tissue.
C . Role of the Liver
The glucose transporter system (GLUT-4) across the membrane
is rate limiting in peripheral tissues that are sensitive
to insulin (muscle, fat). In the liver, however, glucose
moves freely across the plasma membrane, so this process
is not rate limiting at this point. At a blood glucose level
of approximately 8.33 mmol/l (150 mg/dl), the liver does
not take up or supply glucose to the circulation. This level is
termed the “steady state ” or the “glucostatic level ” at which
the mechanisms of normal supply and removal of glucose
are operating at equal rates. Above 8.33 mmol/l (150 mg/dl),
glucose removal is greater than supply, and below
8.33 mmol/l (150 mg/dl), glucose supply is greater than
removal. But the fasting blood glucose level in most animals
is about 5 mmol/l (90 mg/dl). This means that the liver supplies
glucose throughout most of a day except for the few
periods during the day when blood glucose is greater than
the steady-state level of 8.33 mmol/l (150 mg/dl). These
periods are the few hours after each meal during a day.