Major hormones that take part in carbohydrate metabolism are described below:
1. Role of Insulin:
The principal effect of insulin on carbohydrate metabolism is to increase the utilisation of glucose by most tissues. The most important effect of insulin is to increase the rate of glycogen formation. It has been described earlier that insulin is secreted from the β-cells of the islets of Langerhans. It should be borne in mind that the degree of insulin activity and probably the actual production of insulin by the β-cells of the pancreatic islets are effected by the level of blood sugar.
Hyperglycaemia stimulates the pancreas to produce the increased quantity of insulin and if the hyperglycaemia is maintained for a longer period then the permanent damage to the β-cells may ensue and thus permanent diabetes prevails. But it is difficult to say that the hypoglycaemia leads to decrease in insulin secretion in same level. Because during such state adrenaline is secreted and this hormone thus masks the effect of insulin on liver glycogen.
There are other factors which either suppress the production of insulin or may render its action less effective. Growth hormone, glucocorticoids (cortisone and hydrocortisone) and also thyroxine act in such process. There is evidence that growth hormone and glucocorticoids inhibit phosphorylation of glucose by affecting hexokinase activity. These two hormones have got no action on the entry of glucose into the cells.
Glucagon, the α-cell hormone of pancreatic islets and also of gastro-intestinal tract seems to counteract the insulin by exhaustion atrophy of β-cells. Alloxan also counteracts the insulin by damaging the β-cells.
The insulin is mostly concerned with the utilisation of glucose by the tissues and this involves the phosphorylation in which the chain of conversions of glucose and its combination is controlled by a series of enzymes of which hexokinase is an important one. Insulin stimulates the catalytic action of hexokinase.
Insulin has been found to increase the glycogen synthetase activity in muscle. It is claimed that considerably more blood sugar is converted to fatty acids and eventually deposited in the fat depots than that which is turned into tissue glycogen. Insulin increases the conversion of sugar to fatty acids.
Furthermore, formation of liver glycogen is quantitatively higher than the formation of tissue glycogen. The influence of insulin on carbohydrate metabolism has been presented schematically in Fig. 10.18.
2. Role of Glucagon:
Glucagon is known as hyperglycaemic—glycogenolytic factor (HGF). Main effect of glucagon on carbohydrate metabolism is to increase the breakdown of liver glycogen to glucose and hence hyperglycaemia. It does not cause the breakdown of muscle glycogen. Glucagon is secreted from the a-cells of the islets of Langerhans, walls of duodenum and stomach. If glucose is placed in the gastro-intestinal tract then glucagon is secreted from the gastro-intestinal tract directly in the circulation.
Glucagon raises the blood glucose level by stimulating the adenyl cyclase in the liver leading to the formation of cyclic AMP that activates the phosphorylase. Glucagon has got no effect on muscle phosphorylase. Due to action of glucagon on adenyl cyclase, cyclic AMP is formed from ATP. The cyclic AMP thus activates the phosphorylation process of liver glycogen and thus glucose is formed.
Besides this, glucagon also stimulates the process of neoglucogenesis from available amino acids in the liver. Thus increased activity of glucagon increases the blood glucose level which may indirectly stimulate the β-cells activity for the production of excess insulin. Thus prolonged treatment with glucagon causes exhaustion of β-cells and diabetes is produced. Role of glucagon on carbohydrate metabolism has been presented schematically in Fig. 10.19.
3. Growth Hormone:
It is established that growth hormone opposes the hexokinase mechanism, so that the phosphorylation of glucose is depressed causing hyperglycaemia. This hyperglycaemia causes secretion of insulin from the β-cells. Prolonged effect of growth hormone may eventually exhaust the β-cells. Histologically it is proved that α-cells remains unaffected when the β-cells are damaged due to prolonged glucagon therapy. Role of growth hormone on carbohydrate metabolism has been presented schematically in Fig. 10.20.
4. Role of Adrenal Glucocorticoids:
Like growth hormone adrenal glucocorticoids also elevate the blood sugar level. It is claimed that these hormones produce the hyperglycaemic effect by increased neoglucogenesis in the liver. It also produces hyperglycaemia by decreasing the glucose utilisation in the liver and peripheral tissue possible through the inhibition of phosphorylation. In patients with adrenal insufficiency, the blood glucose-lowering effect of insulin is greatly enhanced. In experimental diabetes, adrenalectomy may markedly ameliorate the diabetic state.
In cats and rats after bilateral adrenalectomy, the carbohydrate reserves of the liver and muscles are depleted and hypoglycaemia is produced. But this hypoglycaemic condition is corrected only when corticoids and glucose together, but not glucose only is provided.
5. Role of Epinephrine (Adrenaline):
Epinephrine increases the blood sugar level and this is one of the most important factors in the normal organism for counteracting the hypoglycaemic action of insulin. Epinephrine causes rapid breakdown of liver glycogen to glucose with the production of hyperglycaemia. In muscle, the epinephrine causes the breakdown of glycogen to lactic acid.
Epinephrine is released as an emergency in response to emotional excitement, injury, fright, stress, exercise, etc., and consequently augments blood sugar. Hypoglycaemia from any cause leads to secretion of epinephrine from adrenal medulla and brings the blood glucose level back to normal. Epinephrine exerts its hyperglycaemic effects by increasing the rate of glycogenolysis in the liver and muscles.
Muscle glycogen is not directly available for the replenish of glucose. By the action of epinephrine, both liver and muscle glycogen are converted into hexose phosphate. In the liver, glucose is formed by the action of phosphatase on the hexose phosphate. But the enzyme, phosphatase, is lacking in muscle and for this reason it has to complete the whole glycolytic process with the formation of lactic acid.
Some amount of lactic acid may be transformed into liver glycogen which under the action of epinephrine or glucagon, may be converted into glucose. So the ultimate action of epinephrine on the muscle glycogen is the increased deposition of liver glycogen. The breakdown of the liver and muscle glycogen under the action of epinephrine takes place through the activation of adenyl cyclase that catalyses the formation of cyclic AMP.
Epinephrine also influences the carbohydrate metabolism indirectly by stimulating the adenophysis in releasing the ACTH. ACTH on the other hand augments the release of glucocorticoids from the adrenal cortex. This is observed in emergency, stress, fright, exercise, hypoglycaemia, etc. Insulin and epinephrine play important part in the homeostatic regulation of blood sugar. Because hypoglycaemia stimulates the secretion of epinephrine whereas hyperglycaemia stimulates the secretion of insulin.
Summarily, epinephrine elevates the blood sugar in three ways:
(i) By mobilising the carbohydrate stores of the liver;
(ii) By indirect formation of glucose from muscle glycogen; and
(iii) By excessive formation of glucocorticoids indirectly through liberation of ACTH.
6. Role of Posterior Pituitary Hormones (Vasopressin and Oxytocin):
A large dose of vasopressin and oxytocin raise the blood sugar level temporarily. In rabbits vasopressin is more effective in raising the blood sugar level, whereas in dogs oxytocin has greater hyperglycaemic effect.
7. Role of Thyroid Hormones:
Thyroid hormones increase the glucose absorption from the intestine. The rate of glucose absorption from the intestine is decreased in hypothyroidism. The principal diabetogenic effect of thyroid hormones is possibly due to this increased absorption of glucose from the gut. The hormone also depletes some liver glycogen. Administrations of thyroid hormones to normal animals do not cause immediate effect on blood sugar but liver glycogen is depleted within six to eight hours.
In hyperthyroidism the diabetic condition is aggravated but thyroidectomy markedly decreases the intensity of the diabetes. Rate of protein catabolism is increased by excessive thyroid hormone and for this reason increased hyperglycaemia is observed due to neoglucogenesis from amino acids. Besides this, the thyroid hormones sensitise the adrenaline and the hepatic depletion of glycogen may be the indirect effect of adrenaline by thyroid hormones. Thyroid hormones also raise the renal threshold for glucose.
8. Role of Anterior Pituitary Hormones:
Like growth hormone, the anterior pituitary hormones ACTH and TSH may have some indirect role on the glucose metabolism through acting on the respective target organs. Direct role on the metabolism is possible lacking.
9. Role of Prolactin:
Has got some anti-insulin effect. It reduces the sensitivity of the animals to insulin. The diabetogenic action of prolactin is probably due to this desensitisation of animals to insulin. After hypophysectomy, the blood sugar level is reduced but administration of prolactin raises the level towards normal.
10. Role of Sex Hormones:
Female sex hormones, oestrone and oestradiol, decrease the diabetic condition possible by stimulating the secretion of insulin.
Male sex hormones, testosterone also markedly increases the severity of the diabetic condition of the castrated animals.
The endocrine control of carbohydrate metabolism has been presented schematically in Fig. 10.21.
