Module 2_Endocrine

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Introduction of Endocrinology.

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Endocrine System:

Endocrine System The Chemical Coordination System

Glands:

Glands Gland is an organ in an animal's body that synthesizes a substance for release such as hormones, often into the bloodstream or into cavities inside the body or its outer surface.

Exocrine:

Exocrine Glands that secrete their products via a duct, the glands in this group can be divided into three groups: Apocrine glands - a portion of the secreting cell's body is lost during secretion. Apocrine gland is often used to refer to the apocrine sweat glands, however it is thought that apocrine sweat glands may not be true apocrine glands as they may not use the apocrine method of secretion. Holocrine glands - the entire cell disintegrates to secrete its substances (e.g., sebaceous glands) Merocrine glands - cells secrete their substances by exocytosis (e.g., mucous and serous glands). Also called "eccrine."

Types of Exocrine:

Types of Exocrine Apocrine Holocrine

Types of Exocrine:

Types of Exocrine By type of secretory product Serous glands - secrete a watery, often protein-rich product. Mucous glands - secrete a viscous product, rich in carbohydrates (e.g., glycoproteins). Sebaceous glands - secrete a lipid product. Shape If the gland retains its shape as a tube throughout it is termed a tubular gland . In the second main variety of gland the secretory portion is enlarged and the lumen variously increased in size. These are termed alveolar or saccular glands .

Endocrine:

Endocrine Endocrine system is an integrated system of small organs which involve the release of extracellular signaling molecules known as hormones The field of medicine that deals with disorders of endocrine glands is endocrinology

Autocrine:

Autocrine

Paracrine:

Paracrine

Types:

Types

Pituitary Gland:

Pituitary Gland The pituitary gland , or hypophysis , is an endocrine gland about the size of a pea that sits in a small, bony cavity in middle cranial fossa at the base of the brain. The pituitary gland secretes hormones regulating homeostasis, including trophic hormones that stimulate other endocrine glands. It is functionally connected to the hypothalamus by the median eminence.

Pituitary Gland:

Pituitary Gland

Functions:

Functions Pituitary hormones help control some of the following body processes: Growth Blood pressure Some aspects of pregnancy and childbirth including stimulation of uterine contractions during childbirth Breast milk production Sex organ functions in both women and men Thyroid gland function The conversion of food into energy (metabolism) Water and osmolarity regulation in the body.

Thyroid:

Thyroid The thyroid is one of the largest endocrine glands in the body. This gland is found in the neck just below the laryngeal prominence. The thyroid controls how quickly the body burns energy, makes proteins, and how sensitive the body should be to other hormones.

Thyroid:

Thyroid

Hormones:

Hormones Principally thyroxine (T4) and triiodothyronine (T3) These hormones regulate the rate of metabolism and affect the growth and rate of function of many other systems in the body. Iodine is an essential component of both T3 and T4. The thyroid also produces the hormone calcitonin, which plays a role in calcium homeostasis

Adrenal or Supra-Renal:

Adrenal or Supra-Renal The adrenal glands (also known as suprarenal glands ) are the triangle-shaped endocrine glands that sit on top of the kidneys. They are chiefly responsible for regulating the stress response through the synthesis of corticosteroids and catecholamines, including cortisol and adrenaline.

Adrenal or Supra-Renal:

Adrenal or Supra-Renal

Pancreas:

Pancreas The pancreas is a gland organ in the digestive and endocrine systems of vertebrates. It is both exocrine (secreting pancreatic juice containing digestive enzymes) and endocrine (producing several important hormones, including insulin, glucagon, and somatostatin).

Pancreas:

Pancreas 1: Head of pancreas 2: Uncinate process of pancreas 3: Pancreatic notch 4: Body of pancreas 5: Anterior surface of pancreas 6: Inferior surface of pancreas 7: Superior margin of pancreas 8: Anterior margin of pancreas 9: Inferior margin of pancreas 10: Omental tuber 11: Tail of pancreas 12: Duodenum

Areas of Pancreas:

Areas of Pancreas Appearance Region Function Light staining circles (islets of Langerhans) Endocrine pancreas Secretes hormones that regulate blood glucose levels Darker surrounding tissue Exocrine pancreas Produces enzymes that break down digestible foods

Islets of Langerhans:

Islets of Langerhans Exocrine Islets of Langerhans

Exocrine Part:

Exocrine Part Name of cells Exocrine secretion Primary signal Centroacinar cells bicarbonate ions Secretin Basophilic cells digestive enzymes (pancreatic amylase, Pancreatic lipase, trypsinogen, chymotrypsinogen, etc.) CCK

Endocrine Part (Islets):

Endocrine Part (Islets) Name of cells Endocrine product % of islet cells Representative function beta cells Insulin and Amylin 50-80% lower blood sugar alpha cells Glucagon 15-20% raise blood sugar delta cells Somatostatin 3-10% inhibit endocrine pancreas PP cells Pancreatic polypeptide 1% inhibit exocrine pancreas

Insulin:

Insulin Insulin is a peptide hormone composed of 51 amino acid residues. It is produced in the Islets of Langerhans in the pancreas. The name comes from the Latin insula for "island". Insulin's genetic structure varies marginally between species of animal. Insulin from animal sources differs somewhat in regulatory function strength (i.e., in carbohydrate metabolism) in humans because of those variations. Porcine (pig) insulin is especially close to the human version.

Productions of Insulin:

Productions of Insulin

Actions of Insulin:

Actions of Insulin

Actions on human metabolism :

Actions on human metabolism Control of cellular intake of certain substances, most prominently glucose in muscle and adipose tissue (about ⅔ of body cells). Increase of DNA replication and protein synthesis via control of amino acid uptake. Modification of the activity of numerous enzymes (allosteric effect).

Actions:

Actions Increased glycogen synthesis insulin forces storage of glucose in liver (and muscle) cells in the form of glycogen; lowered levels of insulin cause liver cells to convert glycogen to glucose and excrete it into the blood. This is the clinical action of insulin which is directly useful in reducing high blood glucose levels as in diabetes. Increased fatty acid synthesis insulin forces fat cells to take in blood lipids which are converted to triglycerides; lack of insulin causes the reverse. Increased esterification of fatty acids forces adipose tissue to make fats (i.e., triglycerides) from fatty acid esters; lack of insulin causes the reverse. Increased amino acid uptake forces cells to absorb circulating amino acids; lack of insulin inhibits absorption. Increased potassium uptake forces cells to absorb serum potassium; lack of insulin inhibits absorption. Arterial muscle tone forces arterial wall muscle to relax, increasing blood flow, especially in micro arteries; lack of insulin reduces flow by allowing these muscles to contract.

Actions:

Actions Decreased proteinolysis forces reduction of protein degradation; lack of insulin increases protein degradation. Decreased lipolysis forces reduction in conversion of fat cell lipid stores into blood fatty acids; lack of insulin causes the reverse. Decreased gluconeogenesis decreases production of glucose from non-sugar substrates, primarily in the liver (remember, the vast majority of endogenous insulin arriving at the liver never leaves the liver); lack of insulin causes glucose production from assorted substrates in the liver and elsewhere.

Blood Glucose Regulation:

Blood Glucose Regulation There are two types of mutually antagonistic metabolic hormones affecting blood glucose levels: Catabolic hormones (such as glucagon, growth hormone, and catecholamines), which increase blood glucose. Anabolic hormone (insulin), which decreases blood glucose.

Insulin Release in Blood:

Insulin Release in Blood Beta cells in the islets of Langerhans are sensitive to variations in blood glucose levels through the following mechanism

PowerPoint Presentation:

Glucose enters the beta cells through the glucose transporter GLUT2 Glucose goes into the glycolysis and the respiratory cycle where multiple high-energy ATP molecules are produced by oxidation Dependent on ATP levels, and hence blood glucose levels, the ATP-controlled potassium channels (K+) close and the cell membrane depolarizes On depolarisation, voltage controlled calcium channels (Ca2+) open and calcium flows into the cells Significantly increased amounts of calcium in the cells causes release of previously synthesised insulin, which has been stored in secretory vesicles

Insulin Activation:

Insulin Activation Activation of insulin receptors leads to internal cellular mechanisms that directly affect glucose uptake by regulating the number and operation of protein molecules (GLUT 4 – i.e,Glucose transporter 4) in the cell membrane that transport glucose into the cell.

Activation by Insulin:

Activation by Insulin

PowerPoint Presentation:

Insulin GLUT4 glucose

PowerPoint Presentation:

GLUT4 glucose Insulin

Degradation:

Degradation Degradation normally involves endocytosis of the insulin-receptor complex followed by the action of insulin degrading enzyme. Most insulin molecules are degraded by liver cells.

C-Peptide:

C-Peptide C-peptide is a peptide which is made when proinsulin is split into insulin and C-peptide. They split when proinsulin is released from the pancreas into the blood in response to a rise in serum glucose - one C-peptide for each insulin molecule. C-peptide is the abbreviation for "connecting peptide".

Functions:

Functions C-peptide functions in repair of the muscular layer of the arteries. C-peptide also exerts beneficial therapeutic effects on many complications associated with diabetes mellitus, such as for instance diabetic neuropathy and other diabetes-induced ailments. In the kidneys, C-peptide prevents diabetic nephropathy and in the heart blood flow is improved in diabetic patients. In spite of these physiological functions, C-peptide is actually removed from pharmaceutical preparations of insulin sold by drug companies when they manufacture the synthetic human insulin that is in widescale clinical usage today.

Use:

Use Newly diagnosed diabetes patients often get their C-peptide levels measured, to find if they are type 1 diabetes or type 2 diabetes. The reason that the C-peptide levels are measured instead of the insulin levels themselves is because insulin concentration in the portal vein ranges from two to ten times higher than in the peripheral circulation. The liver extracts about half the insulin reaching it (the plasma), but this varies with the nutritional state. The pancreas of patients with type 1 diabetes is unable to produce insulin and they will therefore usually have a decreased level of C-peptide, C-peptide levels in type 2 patients is normal or higher than normal. Measuring C-peptide in patients injecting insulin can help to determine how much of their own natural insulin these patients are still producing.

Glucagon:

Glucagon Produced by the pancreas, it is released when the glucose level in the blood is low (hypoglycemia), causing the liver to convert stored glycogen into glucose and release it into the bloodstream. It instructs the body's cells to take in glucose from the blood in times of satiation.

Production:

Production The hormone is synthesized and secreted from alpha cells (α-cells) of the islets of Langerhans, which are located in the endocrine portion of the pancreas. The alpha cells are located in the outer rim of the islet.

Regulatory Mechanism:

Regulatory Mechanism Increased secretion of glucagon is caused by: Decreased plasma glucose Increased catecholamines - norepinephrine and epinephrine Increased plasma amino acids (to protect from hypoglycemia if an all protein meal consumed) Sympathetic nervous system Acetylcholine Cholecystokinin

Regulatory Mechanism:

Regulatory Mechanism Decreased secretion of glucagon (inhibition) is caused by: Somatostatin Insulin

Function:

Function Glucagon helps maintain the level of glucose in the blood by binding to glucagon receptors on hepatocytes, causing the liver to release glucose - stored in the form of glycogen - through a process known as glycogenolysis. Glucagon then encourages the liver to synthesize additional glucose by gluconeogenesis. This glucose is released into the bloodstream. Increased free fatty acids and ketoacids into the blood Increased urea production

Mode of Action:

Mode of Action

Use:

Use An injectable form of glucagon is vital first aid in cases of severe hypoglycemia when the victim is unconscious or for other reasons cannot take glucose orally. The dose for an adult is typically 1 milligram, and the glucagon is given by intramuscular, intravenous or subcutaneous injection, and quickly raises blood glucose levels. Glucagon can also be administered intravenously at 0.25 - 0.5 unit.

Blood Sugar:

Blood Sugar Blood sugar is a term used to refer to the amount of glucose in the blood. Glucose, transported via the bloodstream, is the primary source of energy for the body's cells. Blood sugar concentration, or glucose level, is tightly regulated in the human body. Normally, the blood glucose level is maintained between about 4 and 8 mmol/L (70 to 150 mg/dL).

Blood Sugar:

Blood Sugar Failure to maintain blood glucose in the normal range leads to conditions of persistently high ( hyperglycemia ) or low ( hypoglycemia ) blood sugar. Diabetes mellitus, characterized by persistent hyperglycemia of several causes, is the most prominent disease related to failure of blood sugar regulation. Only glucose levels are regulated via insulin and glucagon.

Blood Glucose Regulation:

Blood Glucose Regulation

Other Hormones Influencing Blood Glucose:

Other Hormones Influencing Blood Glucose Hormone Tissue of Origin Metabolic Effect Effect on Blood Glucose Insulin Pancreatic β Cells 1) Enhances entry of glucose into cells; 2) Enhances storage of glucose as glycogen, or conversion to fatty acids; 3) Enhances synthesis of fatty acids and proteins; 4) Suppresses breakdown of proteins into amino acids, of adipose tissue into free fatty acids. Lowers Somatostatin Pancreatic D Cells 1) Suppresses glucagon release from α cells (acts locally); 2) Suppresses release of Insulin, Pituitary tropic hormones, gastrin and secretin. Raises Glucagon Pancreatic α cells 1) Enhances release of glucose from glycogen; 2) Enhances synthesis of glucose from amino acids or fatty acids. Raises Epinephrine Adrenal medulla 1) Enhances release of glucose from glycogen; 2) Enhances release of fatty acids from adipose tissue. Raises Cortisol Adrenal cortex 1) Enhances gluconeogenesis; 2) Antagonizes Insulin. Raises ACTH Anterior pituitary 1) Enhances release of cortisol; 2) Enhances release of fatty acids from adipose tissue. Raises Growth Hormone Anterior pituitary Antagonizes Insulin Raises Thyroxine Thyroid 1) Enhances release of glucose from glycogen; 2) Enhances absorption of sugars from intestine Raises

The GLUTs:

The GLUTs Glucose Transporters

Glucose Transporters:

Glucose Transporters GLUTs are integral membrane proteins which contain 12 membrane-spanning helices with both the amino and carboxyl termini exposed on the cytoplasmic side of the plasma membrane.

Classes:

Classes Class I (Glucose Transporter) GLUT1 GLUT2 GLUT3 GLUT4 Classes II (Fructose Transporter) GLUT5 GLUT7 GLUT9 GLUT11

The GLUT Cycle:

The GLUT Cycle

The PPARs:

The PPARs Peroxisome proliferator-activated receptors

Peroxisome proliferator-activated receptors :

Peroxisome proliferator-activated receptors A group of nuclear receptor isoforms that induce the proliferation of peroxisomes in cells, they are intimately connected to cellular metabolism (carbohydrate, lipid and protein) and cell differentiation.

PPARs :

PPARs α (alpha) - expressed in liver, kidney, heart, muscle, adipose tissue, and others. γ (gamma) - although transcribed by the same gene, this PPAR exists in three forms: γ1 - expressed in virtually all tissues, including heart, muscle, colon, kidney, pancreas and spleen. γ2 - expressed mainly in adipose tissue (30 amino acids longer) γ3 - expressed in macrophages, white adipose tissue. δ (delta) - expressed in many tissues but markedly in brain, adipose tissue and skin.

PPAR Mechanism of Action:

PPAR Mechanism of Action

PPARγ Activation:

PPAR γ Activation Insulin resistance is decreased Adipocyte differentiation is modified Leptin levels decrease (leading to an increased appetite) Levels of certain interleukins (e.g. IL-6) fall Adiponectin levels rise

End of Module 2:

End of Module 2

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