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

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Chapter | 3 Carbohydrate Metabolism and Its Diseases
utilization by increasing enzyme catalyzed reactions in
liver cells.
In nerve cells, insulin binds to receptors and promotes
membrane transport of glucose, but in this case, the membrane
transport system itself appears to be the limiting
factor. Thus, even though the HK system is operating maximally
(Km(G) 5 10 5 ), the limited glucose transport
of about 1.5 mmols/l (27 mg glucose/dl) induces the symptoms
of hypoglycemia: incoordination, disorientation, and
weakness when there is insufficient glucose to compensate
by mass action.
In other cells such as the red blood cell, which also has
the HK system, insulin does not affect glucose metabolism
or limit transport. The HK system is operating maximally
and glucose utilization is sufficient to meet the needs of the
blood cell at all times.
E . Physiological Effects of Insulin
The principal effects of insulin administration to an animal
are summarized in Table 3-5 . The most characteristic finding
following insulin administration is a hypoglycemia.
This occurs regardless of the nutritional state, age, and
other characteristics of the animal and is a net result of
the increased removal of glucose from the plasma into the
tissues. The respiratory quotient (R.Q.) increases toward
unity, indicating that the animal is primarily utilizing carbohydrate.
The consequences of this increased utilization
of glucose follow a pattern of an increase in those constituents
derived from glucose and a decrease in those that are
influenced by increased glucose oxidation. The conversion
of glucose to glycogen, fat, and protein is enhanced,
whereas gluconeogenesis and ketogenesis are inhibited.
The decreases in serum phosphate and potassium levels
that parallel those of blood glucose are presumably due to
their involvement in the phosphorylating mechanisms.
F . Other Pancreatic Islet Hormones
Numerous hormones oppose the action of insulin and, by
doing so, prevent or correct the hypoglycemic effects of insulin.
Hypoglycemia stimulates a number of counterregulatory
hormones including glucagon, epinephrine, and growth hormone.
Norepinephrine and cortisol are less responsive than
the three mentioned.
1 . Glucagon
Glucagon is a polypeptide hormone (Mr 3485 daltons)
secreted by the α (A) cells of the islets. Release of glucagon
is stimulated by hypoglycemia. Glucagon acts only
in the liver where it stimulates glycogenolysis and gluconeogenesis,
thereby increasing blood glucose. The most
important physiological role of glucagon is to promote
hyperglycemia in response to a hypoglycemia. Glucagon
acts only on liver glycogen, unlike epinephrine, which acts
on both liver and muscle glycogen. Like most hormones,
glucagon is first bound to surface receptors on a cell, in
this case, the hepatocyte. Acting through these receptors,
adenylate cyclase is activated, which in turn increases the
amount of cyclic AMP (cAMP). cAMP then activates a
phosphorylase kinase, which activates phosphorylase A,
which in turn hydrolyzes glycogen. Additionally, glucagon
is an insulin secretagogue second only to glucose in the
magnitude of the insulin response it elicits. This insulinreleasing
action of glucagon is the basis for the glucagon
stimulation test (GST), which has been used to evaluate
diabetes in cats ( Kirk et al ., 1993 ).
2 . Somatostatin
Somatostatin is secreted by many cells, including the hypothalamus,
but its major source is the pancreatic δ (D) cells.
TABLE 3-5 Effects of Insulin on Animals
Tissue Increase Decrease
Whole
animal
Anabolism
Food intake
Respiratory quotient
Blood
Glucose
Ketones
Fatty acids
Phosphate
Potassium
Amino acids
Ketone bodies
Enzymes Glucokinase Glucose-6-phosphatase
Phosphofructokinase Fructose 1-6-diphosphatase
Pyruvate kinase Pyruvate carboxylase
Lipoprotein lipase PEP-carboxykinase
AcCoA carboxylase Carnitine acyltransferase
Hormone-sensitive lipase
Liver Glucose oxidation Glucose production
Glycogen synthesis Ketogenesis
Lipid synthesis
Protein synthesis
Muscle (Skeletal/Heart)
Glucose uptake
Glucose oxidation
Glycogen synthesis
Amino acid uptake
Protein synthesis
Potassium uptake
Adipose Glucose uptake
Glucose oxidation
Lipid synthesis
Potassium uptake