Blood Glucose: Regulation and Renal Threshold

In this article we will discuss about the Regulation and Renal Threshold for Blood Glucose.

Regulation of the Blood Glucose:

The stable blood glucose level is maintained by the role of liver, skeletal muscle, kidney, mus­cular exercise and hormones.

Role of Liver:

1. Liver is the pivot of carbohydrate metabo­lism of the whole body. The presence of glucose-6-phosphatase in the liver con­verts glucose-6-phosphate to glucose which diffuses into the blood stream to form the constant and the only source of glucose of blood unless and until glucose is available from the intestine from carbo­hydrate diet.

2. Muscle glycogen cannot be converted to glucose due to the lack of the enzyme glucose-6-phosphatase. Therefore, glycogen is converted to lactic acid which by “Cori Cycle” or “Lactic Acid Cycle” is con­verted to glucose in the liver and the glu­cose is diffused to the blood stream.

3. The liver cells, like other cells, require the oxidation of organic substances to main­tain their own vital functioning. In the ab­sence of fuel glucose, glycogen is dimin­ished and the oxidation of fat occurs form­ing keto acids. Some of the keto acids are utilized for cellular energy. But if the con­centration of keto acids is increased, the keto acids diffuse into the blood stream and accumulate producing ketosis.

4. When the glycogen reservoir diminishes, the amino acids of the body proteins are utilized by the liver for gluconeogenesis.

Role of Skeletal Muscle:

1. Extra-hepatic tissues are relatively imper­meable to glucose and, therefore, insulin is required for the uptake of glucose to these cells.

2. Increased blood glucose promotes glycogenesis and oxidation of glucose in mus­cles. Muscle glycogen does not serve di­rectly as a source of glucose during hypoglycemia. But glucose is supplied to the blood form muscle glycogen by “Cori Cycle” or “Lactic Acid Cycle”.

Role of Kidney:

1. There is considerable evidence that the kidney is able to form glucose from a number of carbohydrate intermediates and also from amino acids.

2. It possesses some capacity for gluconeoge­nesis, although the capacity is minor as compared to that of the liver.

3. When the blood glucose level exceeds the renal threshold level (160-180 mg/100 ml), renal tubules are incapable of reabsorbing all the filtered sugar in glomeruli and the excess glucose is ex­creted in urine. This results in the decrease of blood glucose concentration.

Role of Muscular Exercise:

Muscular exercise promotes the entry of glu­cose into muscle cells and the glucose is utilized by the muscle. Thus, it lowers blood glucose level.

Role of Hormones:

A. Insulin:

1. It is produced by the p-cells of the islets of Langerhans in the pancreas and is liber­ated into the blood by the direct response to hyperglycemia. Insulin is released by amino acids, free fatty acids, ketone food­ies, glucagon, secretin and tolbutamide. Epinephrine and norepinephrine block the release of insulin.

2. It increases the rate of uptake of glucose to tissues.

3. It promotes glycogenesis by stimulating hexokinase and glycogen synthetase and oxidation of glucose by stimulating phosphofructokinase.

4. It decreases hepatic glycogenolysis and gluconeogenesis.

5. It stimulates lipogenesis and protein syn­thesis.

6. It inhibits ketogenesis.

B. Anterior pituitary hormones:

1. The anterior pituitary gland secretes hor­mones that elevate the blood sugar level by antagonizing the action of insulin. They are growth hormone, ACTH and other ‘diabetogenic’ principles.

2. Growth hormone secretion is stimulated by hypoglycemia. It decreases glucose up­take in certain tissues, e.g., muscle.

3. Growth hormone mobilizes free fatty ac­ids from adipose tissue which themselves inhibit glucose utilization.

4. It produces hyperglycemia which stimu­lates secretion of insulin causing exhaus­tion of β-cells.

5. ACTH enhances the release of free fatty acids from adipose tissue and inhibits glu­cose utilization. It also increases blood glucose level by stimulating the secretion of adrenal cortex hormones.

C. Adrenal cortex hormones:

1. Glucocorticoids (11-oxy-steroids) are im­portant in carbohydrate metabolism. They lead to gluconeogenesis by the increased protein catabolism in the tissues, increased hepatic uptake of amino acids and in­creased activity of transaminases in the liver.

2. Glucocorticoids inhibit the utilization of glucose in extra-hepatic tissues. They are antagonists to insulin.

3. Glucocorticoids also increase the forma­tion of glucose in the liver by stimulating glucose-6-phosphatase and fructose-1, 6-bisphosphatase.

D. Epinephrine:

1. Epinephrine, secreted by the adrenal me­dulla, stimulates glycogen breakdown in muscle by increasing phosphorylase ac­tivity.

2. In muscle, glycogen is converted to lactic acid instead of glucose due to the lack of glucose-6-phosphatase. This lactic acid is converted to glucose in the liver by “Cori Cycle” and diffuses into the blood.

3. It diminishes the release of insulin from pancreas.

E. Glucagon:

1. Glucagon is produced by the alpha cells of the islets of Langerhans of the pancreas, being stimulated by hypoglycemia. It causes glycogenolysis by activating phos­phorylase in the liver.

2. It stimulates gIucose-6-phosphatase in the liver to form glucose from glucose-6-phosphate.

3. It enhances gluconeogenesis from amino acids and lactate.

F. Thyroid hormone:

1. Thyroxine has diabetogenic action.

2. It increases the rate of absorption of hexoses and accelerates gluconeogenesis.

3. It stimulates hepatic glycogenolysis with consequent rise in blood sugar. This is due to increased sensitivity to epinephrine.

G. Sex hormones:

Estrogens cause increased liberation of insu­lin and thus decrease blood sugar level. Testosterones also decrease blood sugar level.

Renal Threshold for Glucose:

Glucose is continually filtered by the glomeruli when the blood sugar rises to a high level. But it is completely returned to the blood by the renal tu­bular reabsorption. The reabsorption is influenced by phosphorylation by enzymes.

The capacity of the renal tubules to reabsorb glucose is limited to the rate of about 350 rag/minute. If the filtrate con­tains more glucose than can be reabsorbed, the ex­cess passes into the urine to produce glycosuria.

Glycosuria occurs in the individuals when the venous blood sugar exceeds 160-180 mg/100 ml. This level of the venous blood sugar is said to be the renal threshold for glucose. The maximal rate of reabsorption of glucose by the tubule (TmG- the tubular maximum for glu­cose) is constant. Hence, it is a more accurate meas­urement than the renal threshold which varies with the change of glomerular filtration rate.