Endocrine Physiology (PHS 327)

Physiology Program

College of Health Sciences

Bowen University, Iwo, Nigeria

Dr Michael Olugbenga S

Endocrine Functions

of the Pancreas

Introduction• The pancreas is a unique gland because it has both

exocrine and endocrine glands.

• The acini secretes digestive juice via ducts into the duodenum while the islets of Langerhans secretes hormones into directly into the blood.

• The human pancreas has 1 to 2 million islets of Langerhans.

• The islets are scattered throughout the pancreas, although they are more plentiful in the tail than in the body and head.

Pancreatic Secretions

• Exocrine:

– Secretion of bicarbonate ions

– Digestive enzymes.

• Endocrine:

– islets of Langerhans (2% of pancreas volume)• A cells (25%) secrete Glucagon

• B cells (60%) secrete insulin

• D cells (10%)secrete somatostatin

• F cells secrete the pancreatic polypeptide (PP)

Islets of Langerhans (Pancreatic Islets)

6

Insulin• Insulin was first isolated from the pancreas in 1922

by Banting and Best.

• It is synthesized in the rough endoplasmic reticulum of the beta cells

• Insulin affects fat and protein metabolism almost as much as it does carbohydrate metabolism.

• Insulin Is a Hormone Associated with Energy Abundance

• The half-life of insulin in the circulation in humans is about 5 min.

Functions of Insulin• It is a hypoglycemic hormone. • The net effect of the hormone is storage of carbohydrate,

protein, and fat. Therefore, insulin is appropriately called the “hormone of abundance.”

• Insulin Promotes Muscle Glucose Uptake and Metabolism• Storage of Glycogen in Muscle• Insulin Promotes Liver Uptake, Storage, and Use of Glucose• Insulin Promotes Conversion of Excess Glucose into Fatty Acids

and Inhibits Gluconeogenesis in the Liver• Insulin Promotes Fat Synthesis and Storage• Insulin Deficiency Increases Use of Fat for Energy• Insulin Deficiency Causes Lipolysis of Storage Fat and Release of

Free Fatty Acids• Insulin Deficiency Increases Plasma Cholesterol and

Phospholipid Concentrations• Excess Usage of Fats During Insulin Lack Causes Ketosis and

Acidosis

Regulation of Insulin

EATING, hyperglycemia (>110mg%)

Beta cells secrete insulin

increased glucose uptake into body cells increase glycogenesis(skeletal muscle, liver) increased lipogenesis

normoglycemia (

Stimulators of Insulin secretion• Glucose

• Some aminoacids

• Ketone bodies

• GIT hormones mainly GIP

• Parasympathetic stimulation

• Theophylline

• Sulphonylureas

Inhibitors of Insulin secretion• Somatostatin

• Sympathetic stimulation (a receptors)

• Diazoxide

• Hypokalaemia

• Insulin

Metabolic effects of Insulin

• (1) Carbohydrates:

– Enhancing glucose uptake in most cells (muscles, adipose tissues, bone, skin, mammary glands, others)

– Enhancing glucose entry into liver cells

– Increasing glycogen synthesis in the muscles and liver cells

– Decreasing glucose output from the liver

• (2) Fat:

– Insulin stimulates LIPOGENESIS in the liver cells and adipose tissue

– Insulin prevents LIPOLYSIS in adipose tissue

– Insulin decreases KETOGENESIS in the liver cells and increase the uptake of KETONE BODIES by the skeletal muscles

(3) Proteins:Insulin exert an ANABOLIC EFFECT by increasing the protein content in the muscles and liver by:

Increasing the UPTAKE of the amino-acids into the muscle cellsIncreasing PROTEIN SYNTHESIS in the liver

Insulin Actions

LiverSkeletal Muscle

Adipocytes

Intestine & Pancreas

InsulinInsulin

Insulin

Growth effect

• INSULIN + GH are essential for normal growth (ANABOLIC effect). Thus insulin has a growth promoting effect.

Effect of insulin and glucagon on glucose

CONSEQUENCES OF INSULIN DEFICIENCY

• In humans, insulin deficiency is a common pathologic condition.

• In animals, it can be produced by pancreatectomy;

•by administration of alloxan, streptozocin, or other toxins that in appropriate doses cause selective destruction of the B cells of the pancreatic islets;

•by administration of drugs that inhibit insulin secretion;

•and by administration of anti-insulin antibodies.

GLUCOSE TOLERANCE

•In diabetes, glucose piles up in the bloodstream, especially after meals.

•If a glucose load is given to a diabetic, the plasma glucose rises higher and returns to the baseline more slowly than it does in normal individuals.

•The response to a standard oral test dose of glucose, the oral glucose tolerance test, is used in the clinical diagnosis of diabetes.

•Impaired glucose tolerance in diabetes is due in part to reduced entry of glucose into cells (decreased peripheral utilization).

•In the absence of insulin, the entry of glucose into skeletal, cardiac, and smooth muscle and other tissues is decreased.

• Glucose uptake by the liver is also reduced, but the effect is indirect. Intestinal absorption of glucose is unaff ected, as is its reabsorption from the urine by the cells of the proximal tubules of the kidneys.

Glucose uptake by most of the brain and the red blood cells is also normal.

The second and the major cause of hyperglycemia in diabetes is derangement of the glucostatic function of the liver

Diabetes Mellitus• The constellation of abnormalities caused by insulin deficiency is called diabetes

mellitus

• The cause of clinical diabetes is always a deficiency of the effects of insulin at the tissue level. Type 1 diabetes, or insulin-dependent diabetes mellitus (IDDM), is due to insulin

deficiency caused by autoimmune destruction of the beta-cells in the pancreatic islets, and it accounts for 3–5% of cases and usually presents in children.

• Type 2 diabetes, or non-insulin-dependent diabetes mellitus (NIDDM), is characterized by the dysregulation of insulin release from the beta-cells, along with insulin resistance in peripheral tissues such as skeletal muscle, brain, and liver.

• Diabetes is characterized by:Polyuria (passage of large volumes of urine),Polydipsia (excessive drinking), Weight loss in spite of polyphagia (increased appetite), Hyperglycemia,Glycosuria,ketosis, acidosis, and coma

The fundamental biochemical defects to which most of the abnormalities of diabetes can be traced are :

(1) reduced entry of glucose into various “peripheral” tissues and

(2) increased liberation of glucose into the circulation from the liver.

Therefore, there is an extracellular glucose excess and, in many cells, an intracellular glucose deficiency—a situation that has been called “starvation in the midst of plenty.”

Also, the entry of amino acids into muscle is decreased and lipolysis is increased.

THERAPEUTIC HIGHLIGHTS

In type 1 diabetes, the mainstay of therapy is provision of exogenous insulin, carefully titrated to dietary intake of glucose.

In type 2 diabetes, lifestyle changes such as alterations in the diet or increased exercise can often delay symptoms in early disease, but these are difficult to secure.

Insulin-sensitizing drugs represent second-line agents

Diagnosis of Diabetes

1. Fasting blood glucose measurement after 12 hour overnight fast2. Oral glucose tolerance test3. Measurement of glycated hemoglobin (HbA Ic) :

When plasma glucose is episodically elevated over time, small amounts of hemoglobin A are nonenzymatically glycated to form HbA Ic.

Careful control of the diabetes with insulin reduces the amount formed and consequently HbA Ic concentration is measured clinically as an integrated index of diabetic control for the 4- to 6-weeks period before the measurement.