Biological Chemistry - Berezov T. T., Korovkin B. F. 1998

Carbohydrate Metabolism
Disorders of Carbohydrate Metabolism

In certain conditions, an elevated Blood Glucose Level—hyperglycemia—as well as a decreased glucose concentration—hypoglycemia—can be observed. Hyperglycemia is a fairly common symptom of various disorders, primarily those associated with Endocrine System pathology.

Diabetes Mellitus. Insulin plays a major role in regulating Glycolysis and Gluconeogenesis. Insulin deficiency leads to a condition known as diabetes mellitus: blood glucose concentration increases (hyperglycemia), glucose appears in the urine (glucosuria), and Liver Glycogen content decreases. At the same time, Muscle tissue loses its ability to utilize blood glucose. In the liver, amidst a general decline in biosynthetic processes—METABOLISM/35.html">Protein Biosynthesis and fatty acid synthesis from glucose breakdown products—an enhanced synthesis of gluconeogenesis Enzymes is observed. Administration of insulin to diabetic patients corrects these metabolic shifts: it normalizes the permeability of muscle Cell membranes to glucose and restores the balance between glycolysis and gluconeogenesis. Insulin controls these processes at the genetic level as an inducer of key glycolytic enzymes: hexokinase, Phosphofructokinase, and Pyruvate kinase. Insulin also induces the synthesis of glycogen synthase. Simultaneously, insulin acts as a repressor of key gluconeogenesis enzymes. It should be noted that glucocorticoids serve as Inducers of gluconeogenesis enzyme synthesis. Consequently, under conditions of insulin insufficiency combined with sustained or even elevated corticosteroid secretion (as seen in diabetes), the removal of insulin's regulatory influence leads to a sharp increase in the synthesis and concentration of gluconeogenesis enzymes—particularly phosphoenolpyruvate carboxykinase, which determines the capacity and rate of gluconeogenesis in The Liver and Kidneys.

The Development of hyperglycemia in diabetes can also be viewed as a consequence of The stimulation of metabolic centers in the Central Nervous system by impulses from chemoreceptors in Cells experiencing energy deprivation due to insufficient glucose delivery to the tissues. For The Role of the fructose-2,6-bisphosphate system in Carbohydrate Metabolism regulation, as well as its functional impairments in diabetes mellitus, see Chapter 16.

Hyperglycemia may occur not only in pancreatic disease but also As a result of functional disorders in other Endocrine glands involved in carbohydrate Metabolism regulation. Thus, hyperglycemia can be observed in pituitary disorders, adrenal cortex tumors, and thyroid hyperfunction. Occasionally, hyperglycemia appears during Pregnancy. Finally, hyperglycemia is possible in organic lesions of the central nervous system, cerebrovascular disorders, and inflammatory or degenerative liver diseases. Maintaining blood glucose Homeostasis is, as noted, a critical function of the liver, whose reserve capacity in this regard is exceptionally large. Therefore, hyperglycemia caused by impaired liver function is typically detected only in severe hepatic damage.

Studying the body's reactivity to a glucose load in healthy individuals and patients is of significant clinical interest. Consequently, clinical practice frequently examines time-dependent changes in blood glucose levels, usually after the oral (per os) administration of 50 g or 100 g of glucose dissolved in warm Water—the so-called glucose tolerance test. When evaluating the resulting glycemic curves, attention is paid to the time of the peak rise, the height of this peak, and the time required for glucose concentration to return to baseline. Several indices have been introduced to evaluate glycemic curves, of which the Baudouin index is of primary importance:

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where A is the fasting blood glucose level, and B is the maximum blood glucose concentration following the glucose load. Under normal conditions, this index is approximately 50%. Values exceeding 80% indicate severe carbohydrate metabolism disorders.

Hypoglycemia. Hypoglycemia is frequently associated with decreased function of those endocrine glands whose hyperactivity leads, as noted, to hyperglycemia. Specifically, hypoglycemia can be observed in pituitary cachexia, Addison's disease, and hypothyroidism. A sharp drop in blood glucose levels is noted in pancreatic adenomas due to excessive insulin production by the pancreatic islet ß-cells. In addition, hypoglycemia may be caused by starvation, prolonged physical exertion, or the administration of ß-blockers. Low blood glucose levels are occasionally noted during pregnancy and Lactation.

Hypoglycemia can occur when diabetic patients are administered large doses of insulin. As a rule, it accompanies renal glucosuria resulting from a lowered "renal threshold" for glucose.

Glucosuria. Typically, the presence of glucose in the urine (glucosuria) is the result of impaired carbohydrate metabolism caused by pathological Changes in the Pancreas (diabetes mellitus, acute pancreatitis, etc.). Glucosuria of renal origin, associated with impaired glucose reabsorption in the renal tubules, is less common. As a temporary phenomenon, glucosuria may occur in certain acute infectious and neurological diseases, following epileptic seizures, or after a concussion.

Poisonings with morphine, strychnine, chloroform, and phosphorus are also typically accompanied by glucosuria. Finally, one must keep in mind alimentary glucosuria, gestational glucosuria, and glucosuria associated with emotional stress (emotional glucosuria).

Table 10.2. Types of glycogenoses and their characteristics

Alterations in carbohydrate metabolism under hypoxic conditions. A lag in The rate of pyruvate oxidation behind the rate of glycolysis is most frequently observed in hypoxic conditions resulting from various circulatory or respiratory disorders, altitude sickness, anemia, decreased activity of the tissue oxidation enzyme system in certain infections and intoxications, hypo- and avitaminoses, as well as a consequence of relative Hypoxia during excessive physical exertion.

Enhanced glycolysis leads to the accumulation of pyruvate and lactate in the blood, which is typically accompanied by shifts in acid-base balance and a decrease in the alkaline reserve of the blood. An increased blood content of lactate and pyruvate may also be observed in hepatic parenchymal lesions (late-stage hepatitis, liver cirrhosis, etc.) as a result of inhibited gluconeogenesis in the liver.

Glycogenoses. A number of Hereditary diseases are associated with impaired Glycogen Metabolism. These disorders are termed glycogenoses. They arise due to a deficiency or complete absence of enzymes catalyzing glycogen breakdown or synthesis, and are characterized by its excessive accumulation in various organs and tissues (Table 10.2).

Type I glycogenosis (von Gierke disease) is the most common form, caused by a hereditary defect in the Synthesis of the enzyme glucose-6-phosphatase in the liver and kidneys. The disease is inherited in an autosomal recessive manner. Pathological symptoms appear as early as the first year of a child's life: hepatomegaly and frequently nephromegaly are observed. Hypoglycemia leads to seizures, growth retardation, and potential acidosis. Blood tests reveal elevated levels of lactate and pyruvate. Administration of epinephrine or Glucagon causes significant hyperlacticacidemia but does not induce hyperglycemia, since glucose-6-phosphatase is absent in the liver and free glucose cannot be formed.