Let us Learn about the Disorder of Pancreatic Hormone.
Introduction to Diabetes Mellitus:
Pancreatic hormones, insulin and glucagon maintain homeostatic condition of blood glucose level by antagonistic functions. Failure of insulin secretion may cause a disease diabetes mellitus. Diabetes mellitus means “siphoning of honey” i.e. large volume of urine with high sugar content.
This disease was first reported in Egypt of about 1500 BC. Hypo secretion of insulin occurs due to damage or destruction of B-cells of pancreatic islets. Besides this, there are some other reasons for this disease.
General symptoms of diabetes mellitus:
1. Increased thirst (Polydipsia).
2. Increased frequency of urine (Polyuria)
3. Increased appetite (Polyphagia).
4. Unexpected weight loss.
5. Increased tiredness.
6. Irritability increased.
7. Blurring of eyesight.
8. Increased frequency and extent of infections like boils, skin infection, urinary infection etc.
9. In ladies vulval itching occurs.
10. High blood sugar (Hyperglycemia).
11. Catabolism of protein takes place.
12. Glycogenolysis occurs.
Types of Diabetes Mellitus:
It can be divided into two types:
1. Insulin Dependent Diabetes Mellitus (IDDM) or Type I.
2. Non-insulin Dependent Diabetes Mellitus (NIDDM) or Type II.
Type l-insulin Dependent Diabetes Mellitus (IDDM):
Causes (Etiology):
It is caused by marked deficiency of insulin or marked decrease in number of insulin secreting cells (β-cells). It is opined that cytotoxic antibodies to β-cells lead to destruction of β-cells. Juvenile onset diabetes develops in youth (within 10-14 years) due to viral infections like mumps, rubella etc. Viral infections may damage β-cells.
Clinical symptoms:
1. Hyperglycemia:
In this condition blood glucose level increases above the normal level of 120 mg/100 ml blood. In this cases utilization of glucose is diminished, uptake of glucose to muscle tissue and adipose tissue become reduced; fall of insulin mediated induction of glucokinase, increased glycogenolysis and increased gluconeogenesis. Inhibition glycogenesis takes place.
2. Glucosauria:
In this case blood glucose level exceeds the renal threshold of 180 mg/100 ml blood. In this condition, the renal tubules fail to reabsorb the entire quantity of glucose from glomerular filtrate, thus glucose appears in the urine. The result is the development of polydypsia (increased thirst) and polyuria.
3. Lipogenesis:
Marked decreased lipogenesis occurs in diabetic patients due to decreased synthesis of insulin induced enzymes decreased transfer of citrate from mitochondria to cytoplasm; inhibition acetyl CoA carboxylase etc. ketogenesis.
4. Lepidemia:
Hypo secretion of insulin or damage of β-cells increases plasma lipid level by lipolysis in adipose tissue and β-oxidation in hepatic cells.
5. Protein catabolism:
Hypo secretion of insulin stimulates protein catabolism in skeletal muscles and leads to wasting of muscles and loss of weight in diabetic patient.
6. Ketogenesis:
Deficiency of insulin “may cause-synthesis of ketone bodies like β-hydroxybutyric acid, acetoacetic acid in liver. This accumulation of acids in plasma leads to severe metabolic acidosis.
7. Sorbitol formation:
In diabetic patients, sorbitol is developed form glucose and accumulates in lens tissue of eye, nerve tissue etc. This accumulation may cause development of cataract in lens and neuronal disturbances.
8. K+ imbalance:
K+ influx is reduced into the cells, that in-turn raises the K+ level in plasma. This K+ imbalance may cause death.
Type II-Non-insulin Dependent Diabetes Mellitus (NIDDM):
This type of diabetes mellitus is usually found in adults (above 35 yrs old). NIDDM results from defect of insulin receptors in the target cells. In this condition, normal insulin level present in blood, the fault mostly lies in a reduced binding of insulin to its receptor on the target cell membrane.
Resistance to insulin can be divided into three types
1. Pre-receptor resistance:
This may occur due to (a) Antibodies against insulin.
(b) Mutant insulin structures, like defect in amino acid sequence of p-chain of insulin molecule at one or more positions.
(c) Defect in pro-insulin structure, mutation occurs at cleavage centre of A or B chain.
2. Receptor resistance:
This may be due to:
Type A:
Reduction in number of insulin receptor on target cell, decrease in affinity of the receptor to the hormone, defect in synthesis of receptor by point mutation in insulin receptor gene which prevents processing of the receptor precursor, point mutation also blocks the insertion of mature receptor in the plasma membrane of target cell.
Type B:
Receptor blocked by circulatory antibodies to the receptor.
3. Post receptor resistance:
This is due to:
(i) Decreased capacity of pancreatic β-cells to compensate for the underlying insulin resistance by increased secretion of insulin,
(ii) Possible under expression (down regulation) of β-cell glucose transporters.
(iii) Mutation of the glucokinase gene may prevent uptake and metabolism of glucose necessary for the mechanism of insulin secretion,
(iv) Autoantibodies to the GLUT-2 glucose transporter of β-cells.
Clinical symptoms:
There are about 10 million people with diabetes mellitus in the USA. About 80% of these people have NIDDM. The classic symptoms of polydypsia, polyuria, blurred vision, paresthesia and fatigues are manifestations of hyperglycemia and are therefore, common to both forms of diabetes. However, most individuals with NIDDM show obesity and chronic skin infections.
Special note:
1. Islet cell tumours
(a) Insulinoma:
Severe hyper secretion of insulin may cause severe hypoglycemia, in this condition a tumour like growth occurs by formation of cluster of β-cells. The important symptoms are blurred vision, sweating, weakness, palpitation etc.
Table 12.1: Difference between IDDM and NIDDM
2. Glucagonoma:
Excess secretion of glucagon from α-cells, may cause α-cell tumour. The clinical symptoms are weight loss, decreased blood amino acid levels.
3. Somatostatinoma:
Hyper secretion of somatostatin form D-cell may cause pancreatic tumour. Clinically excess secretion of somatostatin may disturb the function of adenohypophysis, pancreatic islets, and gastrointestinal mucosa.