Insulin: Actions and Regulation | Endocrinology

In this article we will discuss about the action and regulation of insulin.

Actions of Insulin (Figs 6.43, 6.44):

1. On carbohydrate metabolism

2. Fat metabolism

3. Protein metabolism

4. On plasma potassium.

Action on Carbohydrate Metabolism:

i. It is a hypoglycemic agent.

ii. Decreases the blood glucose level.

iii. The normal fasting blood glucose level is in the range of 60-90 mg%.

The actions of insulin on carbohydrate metabolism are:

a. Increasing the peripheral utilization of glucose:

In most of the tissues of the body, for transfer of glucose from ECF to ICF and glycolysis to be brought about inside the cell, insulin is essential. Some of the tissues which do not require insulin for peripheral utilization of glucose are whole of brain except satiety center, RBCs, renal tubules and mucosa of gastrointestinal tract.

During the movement of glucose from ECF to ICF, potassium will also be transferred from ECF to ICF. Because of this, plasma potassium level falls. It is for this reason, when insulin is administered in large doses as done in the treatment of diabetic ketoacidotic coma, along with insulin, potassium should be administered to prevent hypokalemia and its deleterious effects.

Insulin can be also administered, if one has to treat cases of severe hyperkalemia but since insulin is a very powerful hypoglycemic agent, in the treatment of hyperkalemia, along with insulin glucose also must be given to prevent patient developing hypoglycemia and its consequences.

b. Utilization of glucose to supply energy spares the proteins from getting catabolized. This is known as protein sparing effect.

c. It also increases the glucose uptake by the liver and enhances the conversion of glucose to glycogen. This is brought about by enhancing the activity of glycogen synthase. This glycogen gets stored in liver.

d. It also decreases glycogenolysis in liver and muscle tissue. So the breakdown of glycogen to glucose will be less.

e. It decreases gluconeogenesis that is formation of glucose from non-carbohydrate sources, like amino acids and fatty acids.

On Protein Metabolism:

It facilitates the transfer of amino acids from ECF to ICF. The amino acids that have entered the ICF will be utilized for protein synthesis. At the same time, it will also decrease the breakdown of proteins. Incorporation of amino acids into proteins leads to retention of nitrogen in the body and brings about positive nitrogen balance.

The proteins synthesized will be used for growth of tissues and organs. This facilitates the growth, repairing of wounds, adequate resistance against infections (because of immunoglobulins) and gain of weight. In case, the child suffers from juvenile diabetes, growth of the child decreases because of loss of aforesaid actions of insulin on protein metabolism.

On Fat Metabolism:

It is a lipogenetic agent. It acts on the adipose tissue and increases the activity of lipoprotein lipase and decreases the hormone sensitive lipase activity. This leads to increased lipogenesis and decreased lipolysis. The fatty acids are transferred from ECF to ICF in adipose tissue. These fatty acids are converted to neutral fats and triglycerides and stored in adipose tissue.

Deposition of fats will increase the weight of the person. Absence of insulin brings about increase in the free fatty acid levels in circulation. When glucose cannot be utilized to supply energy, the fatty acids are metabolized to supply energy. This brings about increased formation of ketone bodies. Such situation is called as ketoacidosis.

On Plasma Potassium:

Since insulin is involved in transfer of potassium from ECF to ICF, it decreases plasma potassium level.

Regulation of Secretion of Insulin:

1. One of the important factors which regulate insulin secretion is plasma glucose level (Fig. 6.45). More is the plasma glucose level more will be the amount of insulin secreted. The amount of insulin secreted for the same amount of glucose, depends whether glucose is administered orally or intravenously.

Administration of glucose through oral route brings about enhanced insulin secretion than intravenous administration. This is because of the influence of some of the GI tract hormones and vagus nerve influence on the beta cells in islets.

2. Some of the other factors which enhance insulin secretion are amino acids, keto acids, exercise, GI tract hormones, ACh, etc. (Table 6.11).

3. Some of the factors which decrease insulin secretion are somatostatin, potassium depletion, alpha adrenergic stimulation, etc.

Insulin Lack:

i. Administration of toxic substances, like alloxan, streptozotocin, destroys the beta cells of islets of Langerhans and thus lead to insulin lack.

ii. Lack of insulin results in increased blood glucose (hyperglycemia) level.

iii. When blood glucose level exceeds 180 mg% (renal threshold), it leads to glycosuria. That is glucose appears in urine. Hence the condition is known as diabetes mellitus.

iv. When glucose is excreted, since glucose is an osmotically active substance, it drags water also with it. This will give rise to polyuria.

v. In the hypothalamus, there are two centers namely hunger center which is located in the lateral hypothalamic nucleus and ventromedial nucleus which acts as satiety center. Normally, the hunger center activity is under constant inhibitory influence from the satiety center.

The utilization of glucose by satiety center is dependent on insulin. When insulin is absent, the activity of satiety center is depressed. Because of this, the inhibition on the hunger center by satiety center is decreased (disinhibition). Now, the hunger center activity becomes unopposed and gives rise to increased hunger and hence polyphagia.

Pathophysiology of Diabetes Mellitus:

Diabetes mellitus can be of two types namely type I or insulin-dependent diabetes mellitus (IDDM) and type II or non-insulin-dependent diabetes mellitus (NIDDM).

Type I:

i. Younger age of onset.

ii. Severe or absolute insulin deficiency.

iii. Less genetic predisposition.

iv. Loss of beta cells.

v. More prone to ketoacidosis.

Type II:

i. Late onset, > 40 years.

ii. Relative insulin deficiency.

iii. Reduced sensitivity of tissue to insulin.

iv. Genetic predisposition is more.

v. Normal beta cell mass.

vi. Non-ketotic hyperosmolar coma.

Whatever may be type of diabetes, there will be fault in glucose metabolism.

Decreased peripheral utilization and increased hepatic glycogenolysis brings about an increase of blood glucose level:

i. Increased blood glucose (above renal threshold of 180 mg%) level leads to glycosuria.

ii. Glycosuria leads to polyuria (increased urine excretion) since glucose is an osmotically active substance. This type of polyuria differs from polyuria of diabetes insipidus because in diabetes insipidus, the diuresis is termed as water diuresis and the specific gravity of urine will be low.

iii. Increased loss of water along with urine leads to dehydration and resulting in stimulation of thirst center and hence there will be polydypsia (increased drinking).

iv. Unopposed activity of hunger center results in polyphagia (increased eating).

Glycosuria:

a. Polyuria, polydypsia, polyphagia

b. Weightloss inspite of polyphagia

c. 3 polys are very characteristic features of DM.

v. Since the blood glucose level is more and body protein content is less, the person is more susceptible to infection and poor wound healing.

vi. Increased protein catabolism leads to weight loss and poor growth. The amino acids which are the end products of protein catabolism will be used for gluconeogenesis.

vii. In the absence of glucose getting metabolized to supply energy, fats catabolism increases and this gives rise to lipolysis. The beta oxidation of fatty acids brings about increased formation of ketone bodies and lead to ketoacidosis. Ketone bodies can be excreted along with expired air and hence the breath of these patients will have characteristic apple odor.

The cardinal symptoms of diabetes mellitus are shown in Fig. 6.46.

Tests for Diabetes Mellitus:

1. Test for glucose in urine.

2. Test the fasting blood glucose level.

3. Perform oral glucose tolerance test (GTT).

Coma is one of the serious problems of glucose metabolism. The person may get into coma both because of hyperglycemia or hypoglycemia. One of the examples of hypoglycemic coma is improper management of diabetic patients especially when the antidiabetic drug is taken but diet is compromised or drug taken may be more than the required dose. Among the two types of coma, hypoglycemic coma is more dangerous.

The signs and symptoms of hypoglycemic coma are:

1. Dizziness and nervousness due to increased autonomic discharge.

2. Palpitation.

3. Sweating.

4. Weakness.

5. Ataxia that is incoordination of movements.

6. Confusion.

7. Nervousness and apprehension.

8. Tremors.

9. Slurred speech.

10. Convulsions.

How to differentiate whether coma is because of hypo- or hyperglycemia?

When comatose patient is brought into the emergency room, time should not be wasted. Treatment to the patient has to be started as fast as possible. One of the first and foremost things to be done is, when it is not certain that coma is due to hypo- or hyperglycemia, infuse glucose intravenously to the patient.

If coma is because of hypoglycemia, the patient recovers without any further procedure. If coma is due to hyper­glycemia, the patient will not recover and infusion of glucose would not harm the patient anymore. Now the treatment has to be initiated to manage the hyperglycemic coma.

The differences between hyperglycemic and hypoglycemic coma has been detailed in Table 6.12.

Some of the conditions in which glycosuria occurs are:

1. Diabetes mellitus due to problem in glucose metabolism.

2. Renal glycosuria due to problem in function of renal tubules.

3. Alimentary glycosuria occurs in hyperthyroidism. In hyperthyroidism, the rate of absorption of glucose from GI tract is enhanced and this may lead to glycosuria.

4. Picquare glycosuria in which constant stimulation of brainstem area leads to glycosuria.