Pancreas

The pancreas is a gland situated in the upper part of the abdomen, posterior to the stomach, and connected to intestine by a fine tube .

The pancreas main function is to secrete digestive enzymes and hormones such as insulin and glucagons. Pancreas morphology structure was first described by Paul Langerhans in his thesis in 1869 (Volk et al, 1985).

Human pancreas composed of two types of secretory cells.

The endocrine pancreas

The endocrine function of pancreas is performed by the islets of Langerhans.  

Islets of Langerhans

Each islet of Langerhans contains four different types of endocrine cells.

β-cells represent the majority of the endocrine cell population (St-Onge et al, 1999).

Islets of Langerhans

In contrast, α-cells are cells that produce glucagon which raises the blood glucose levels by increasing the rates of glycogen breakdown and glucose release by the liver

On the other hand, δ-cells are cells producing somatostatin peptide hormone.

Finally are the cells that producing the pp hormone which inhibits the gallbladder contractions.

Characteristic Features

-cells -cells - -cells PP-cell

Peptide Hormone

 

 Glucagon Insulin Somatostat-in

Pancreatic

Polypeptide

Location

 

In the periphery of the islets

In the centre

In the periphery of the islets

In posterior lobe of pancreas,

Appearance

 

Uniform in size and have dense granules compared to β-

cells

Have polyhedral core and

pale matrix

Have larger granules than δ- & β-cells

Molecular weight

Number of amino acids

Total volume % in adult

3500

29

15-20

5800

51

70-80

1500

14

5-10

4200

36

15-25

INSULIN

 Insulin has been found in all vertebrates and it has a highly conserved structure (Dodson et al, 1998). It consists of two polypeptide chains, A and B, connected by two disulfide bridges (Dodson et al, 1998).

In human there is a single copy of the insulin gene located on the short arm of chromosome 11 (Docherty et al, 1996 )

It is the chief hormone of the pancreas, secreted by the beta cells. Insulin is a polypeptide having Alpha and Beta amino acid chains. Alpha chain is composed up of 21 amino acids, where as Beta chain contains 30 amino acids. Molecular weight of insulin is about 5800

Figure 2. Pro-insulin, Insulin and C-peptide

ACTIONS OF INSULIN

 

The main action of insulin is to reduce the blood glucose level, when ever it is increased above the normal values.

When the blood glucose level rises to about 120 mg/dl, secretion of insulin rises to about 100 micro-U/minute.

 Insulin reduces the blood glucose level in the following way:

1.  Insulin increases the permeability of the cell membrane for the glucose.

2. Insulin stimulates the conversion of glucose into glycogen in the liver and the skeletal muscles

3. Insulin stimulates the process of lipogenesis to stimulate the synthesis of fatty acids and their storage in the adipose tissues.

4. Insulin prevents the breakdown of proteins, fat, and gluconeogenesis

REGULATION OF THE SECRETION OF THE INSULIN

A part from an increase in the blood glucose level, certain other factors that Stimulates the insulin secretion.

Factors that reduces the secretion of insulin includes the stimulation of sympathetic nervous system. Hyper secretion of adrenaline, cortisol, glucagons and Somatostatin.

Glucagon

It is a polypeptide with a molecular weight of about 3485. It contains 29 amino acids. Glucagon is secreted by the Alpha cells of the islets of Langerhans. Main function of glucagons is to increase the blood glucose level, when ever it is decreased.

This stimulatory effect is carried out in the following way: 

1:Glucagon increases the conversion of glycogen into glucose in the liver and skeletal muscles by a process namedglycogenolysis. 

2:Glucagon stimulates the process of gluconeogenesis, by producing new sugars as a result of the breakdown of the proteins. 

Glucagon

Secretion of glucagons is decreased as a result of an increase in the secretion of insulin and Somatostatin. Exercise is a physiological factor that stimulates the secretion of Glucagon.

Glucagon shows its metabolic action by activating the intracellular enzyme system and formation of second messenger AMP

SOMATOSTATIN 

It is a polypeptide with 14 amino acids. It is secreted by the Delta cells in the Islets of langerhans.  

Somatostatin inhibits the secretion of insulin and glucagons both. It reduces the motility of stomach, duodenum, and gall bladder. 

DISORDERS OF THE PANCREATIC ISLETS

Diabetes is a group of metabolic disorders characterized by abnormal fuel metabolism resulting chiefly in hyperglycemia and dyslipidemia.

Diabetes is a serious disease associated with acute (due to hyperglycemia) and chronic (due to vascular damage) complications

Diabetes is clinically diagnosed if a fasting plasma glucose is ≥ 126 mg/dl more than once or when an individual has symptoms of diabetes and her casual plasma glucose is ≥ 200 mg/dl.

Type 1 diabetes is caused by an autoimmune destruction of the beta cells of the pancreas due to an interplay between genetic and environmental modifiers.

Type 2 diabetes, the most prevalent form of diabetes, is characterized by a combination of insulin resistance and insulin deficiency

The metabolic syndrome is characterized by insulin resistance,central obesity, hypertension, dyslipidemia, and increased risk forcardiovascular and disease death.

Diabetes is a group of metabolic disorders characterized by abnormal fuel metabolism, which results most notably in hyperglycemia and dyslipidemia, due to defects in insulin secretion, insulin action, or both. diabetes.

Diagnosis of Diabetes and Glucose Intolerance

Diabetes is a dysmetabolic disorder affecting multiple bodily functions. Its diagnosis is based on the presence of hyperglycemia. The diagnostic criteria for diabetes were modified in 1997 and again in 2003 by the American Diabetes Association, as shown in Table 1.

Table 1. Diagnosis of Diabetes Mellitus

Glucose Intolerance

Diabetes

Classic symptoms of diabetes PLUS casual plasma glucose ≥ 200 mg/dL or

100 < Morning < FPG 126 mg/dL (IFG)

Morning FPG ≥ 126 mg/dl or

140 < 2-hour PG < ßß200 mg/dL (IGT)

2-hour PG ≥ 200 mg/dl

IFG = impaired fasting glucose, IGT = impaired glucose tolerance. Classic symptoms of diabetes include: polyuria, polydipsia, and unexplained weight loss.

Casual is defined as any time of the day without regard to time since last meal. FPG = fasting plasma glucose, defined as no consumption of food or beverage (other than water) for at least 8 hours.

Classification of Diabetes Based on Etiology

In 1997, the American Diabetes Association revised the nomenclature for the major types of diabetes. The terms insulin dependent diabetes mellitus and non-insulin-dependent diabetes mellitus and their acronyms, IDDM and NIDDM, were eliminated. These terms had frequently resulted in classifying the patient based on treatment rather than etiology.

Type 1 diabetes: pancreatic beta islet cell destruction leading to absolute insulin deficiency Type 1b presents like type 1diabetic ketoacidosis (with DKA), then behaves like type 2 Type 2 diabetes: varying degrees of insulin resistance and insulin deficiency Gestational diabetes

DISORDERS OF THE PANCREATIC ISLETS

TYPES OF DIABETES MELLITUS

Insulin Dependent Diabetes Mellitus (IDDM-Type-I)Type 1 diabetes (DM-1) was previously known as IDDM

(insulin dependent diabetes mellitus) or juvenile-onset diabetes. About 5-10% of patients with diabetes have DM-1.

This type of diabetes mainly occurs in the children and the young adults. Main cause is either deficiency or absence of insulin in the blood, which raises the blood glucose level above normal.  leading to either deficiency or complete stoppage of insulin secretion.

Non-Insulin Dependent Diabetes (NIDDM-Type-II)

Type 2 diabetes (DM-2), previously known as NIDDM or adult-onset diabetes, is the most prevalent form of diabetes, accounting for over 90% of all cases of diabetes. Type 2 diabetes is characterized by varying degrees of insulin resistance and insulin deficiency.

Type II diabetes or adult- onset diabetes occur when the body cannot use the insulin effectively.

Type II diabetic patients can control their blood glucose concentration by regular diets, exercises and oral medication (NIH, 2001). This type is the most common form of diabetes (Edlund, 2001).

Gestational Diabetes

This type of diabetes frequently occurs during the pregnancy and disappears after the delivery. Raised blood glucose level during the pregnancy, generally produces large sized babies. In many cases, still birth is observed or deaths shortly after the birth.

EFFECTS OF DIABETES MELLITUS 

Raised Blood Glucose Level This occurs as a result of a defective absorption of glucose by the cell Membrane.  

Glycosuria, Polyuria and Polydipsia When ever the blood glucose level rises, 100% glucose is not reabsorbed by The glomerulus. As a result, some amount of glucose appears in the glomerular filtrate, which later on is excreted in the urine by producing glycosuria. Excess amount of glucose in the glomerular filtrate, raises the osmotic Pressure, which causes disturbance of water and electrolyte metabolism. result, water reabsorption is reduced, leading to an increase in the formation of urine, with a high specific gravity, due to poor reabsorption of electrolytes like ammonia, sodium and potassium, leading to polyuria. Excess urination leads to severe dehydration, leading to Polydipsia.

Weight Loss

Ketoacidosis

ACUTE COMPLICATIONS OF DIABETES MELLITUS

Diabetic Coma  Main cause of diabetic includes stress, such as pregnancy, microbial infections, and cerebrovascular accident.

Hyperglycemic Coma

This condition more commonly occurs in the IDDM patients. Usually there is over dose of insulin, or the time duration between the two meals or time duration between the insulin therapy and the meal is prolonged. As a result, blood glucose level is abruptly reduced.

In all these conditions, severe hypoglycemia is produced, which affects the the activity of neurons in the brain. As a result, excessive sweating, anxiety, restlessness, mental confusion, difficulty in speech and coma occurs. This is called Hypoglycemic Coma.

LONG TERM COMPLICATIONS OF THE DIABETES MELLITUS

  Diabetic Macroangiopathy  In this condition calcification of the large muscular arteries occurs. In NIDDM cases, these changes may occur at a relatively early age. Myocardial infraction and cerebral ischemia are the most common symptoms

Diabetic Microangiopathy

Micro vascular complications are a significant cause of morbidity. Persistent hyperglycemia is the major cause for the microvascular complications which are highly specific for diabetes.

Retinopathy.

Nephropathy.

peripheral neuropathy.

InfectionsDiabetics are highly susceptible to infections, especially by bacteria andfungi, because the phagocytic activity is depressed in diabetes mellitus. Most frequent type of infections is:  Boils and Carbuncles Vaginal Candidiasis