The following points highlight the two important hormones secreted by islets cells. The hormones are: 1. Insulin 2. Glucagon.
Hormone # 1. Insulin:
It is the active principle of the islets cells. It is albumin in nature having a molecular weight of 35,000. It is hydrolyzed by proteolytic enzymes, hence is not effective orally. It is easily destroyed by alkalies but is relatively stable in slightly acid solutions. The fact that the pancreatic tissue is rich in zinc probably indicates that insulin remains stored in islet cells as a zinc salt. The deficiency causes diabetes mellitus in man.
The effects of the hypo-activity of the gland or removal of pancreas are:
(i) Hyperglycaemia (rise in blood sugar) and glycosuria increase in urinary sugar,
(ii) Depletion of glycogen depots of liver and muscles; lowering of R. Q. (Respiratory Quotient);
(iii) Ketosis (increased formation of ketone bodies);
(iv) The arteriovenous blood sugar difference becomes low indicating that peripheral tissues are not utilising blood sugar.
This results in weakening the animal body with early onset of muscle fatigue and finally ends in death. Banting, Maeleod, Best, and Collip prepared an acid alcoholic extract of the pancreas which permuted these symptoms in a pancreatectomised animal and which could be used to relieve diabetic victims among human beings.
Diabetes mellitus is diagnosed by the above characters and the sufferers are temporarily cured by injecting insulin [Protamine zinc insulin —a salt of zinc, basic protein (Protamine) and insulin].
Functions of Insulin:
Viewing the above ill-effects of the hypo-activity of the islets cells, the following functions are believed to be performed by insulin:
a. Stimulates Glycolysis:
Insulin increases combustion of sugar in the tissues.
It is evident by the following:
(i) In advanced diabetes R.Q. is above 0.7 because of the combustion of fats,
(ii) Low arteriovenous blood sugar difference showing that tissues are not utilising blood sugar, and the difference rises on administration of insulin, and
(iii) Isolated living tissue, when perfused with sugar, shows a diminished power of burning glucose which, however, increases if insulin is added to the perfusing fluid.
b. Stimulates Glycogenesis:
Insulin increases synthesis of glycogen from monosaccharides and lactates both in liver and muscles.
c. Prevents Gluconeogenesis:
Glucose is normally formed from proteins and fats in the liver. But in diabetes the rate of gluconeogenesis is increased. In starving diabetic, Dextrose/Nitrogen ratio is nearly constant, about 3.6 indicating that both sugar and nitrogen are derived from the same source —the proteins. When insulin is given, both sugar and nitrogen excretion falls, indicating that formation of new glucose from proteins has been stopped.
d. Anti-Ketogenic Action:
It prevents formation of ketone bodies. In the deficiency of the hormone (diabetes) more ketone bodies are formed in the liver due to incomplete combustion of fatty acids. On administration of insulin more sugar burns, and liver glycogen content increases displacing the fats: thus ketone formation is prevented by insulin.
Control of Secretion of Islets Cells:
As the removal of pancreas spontaneously leads to diabetes mellitus, it is supposed that insulin is secreted continuously by the islets cells.
However, the control of insulin (quantitatively) is effected as follows:
i. Nervous Control:
There is some evidence that stimulation of vagus increases insulin secretion. Normally blood sugar adjusts the vagal tone and modifies insulin secretion. High blood sugar stimulates and low blood sugar depresses the vagus. But this mechanism is least effective and is only a means for fine adjustment.
ii. Control by Blood Sugar Level:
The blood sugar concentration of arterial blood entering the pancreas is the best controller for the secretion of insulin by islets cells. High blood sugar stimulates while low blood sugar depresses. This action is perhaps direct on the islets tissues independent of nerves.
Thus, blood sugar controls insulin secretion in two ways, i.e. by direct action on the islets and through vagus. However, it is also believed that the pancreotropic hormone of adenohypophysis also controls insulin secretion. But the actual way of control is still unknown.
Hormone # 2. Glucagon:
Kimball and Murlin (1923) demonstrated first of all the presence of glucagon hormone in the pancreatic islets. Produced by a cells glucagon is a polypeptide with a molecular weight of about 3,485.
Glucagon is a diabetogenic hormone and thus is antagonistic to insulin. It promotes glycogenolysis, thus raising blood sugar. It also stimulates gluconeogenesis in conversion of non sugar substances (fats and amino acids) into glucose or glycogen.
The secretion of glucagon is controlled by the blood sugar itself. Low blood sugar stimulates and high blood sugar diminishes its secretion.