Chapter 6-The Endocrine System (PDF)

1 ANATOMY AND PHYSIOLOGY CHAPTER 6: ENDOCRINE SYSTEM BIO 343  OUTLINE 1) OVERVIEW OF THE ENDOCRINE SYSTEM (HORMONES AND THEIR ACTIONS) 2) HYPOTHALAMUS AND PITUITARY GLAND 3) PINEAL GLAND AND THYMUS 4) THYROID, PARATHYROID, AND ADRENAL GLANDS 5) PAN...

1 ANATOMY AND PHYSIOLOGY CHAPTER 6: ENDOCRINE SYSTEM BIO 343  OUTLINE 1) OVERVIEW OF THE ENDOCRINE SYSTEM (HORMONES AND THEIR ACTIONS) 2) HYPOTHALAMUS AND PITUITARY GLAND 3) PINEAL GLAND AND THYMUS 4) THYROID, PARATHYROID, AND ADRENAL GLANDS 5) PANCREATIC ISLETS AND DIABETES 2 INTRODUCTION TO THE ENDOCRINE SYSTEM  The endocrine system is a series of glands, tissues and cells that produce and secrete hormones that the body uses for a wide range of functions  Endocrinology—the study of the endocrine system and the diagnosis and treatment of its disorders  Endocrine glands—organs that are traditional sources of hormones  Hormones—chemical messengers that are transported by the bloodstream and stimulate physiological responses in cells of another tissue or organ, often a considerable distance away Vascular corrosion cast of the blood vessels of the thyroid gland 3  COMMUNICATION IN THE BODY The body has four principal mechanisms of communication between cells Gap junctions—pores in cell membrane allow signaling molecules, nutrients, and electrolytes to move from cell to cell (eg. in smooth and cardiac muscles) Neurotransmitters—released from neurons to travel across synaptic cleft to second cell (described in the previous chapters) Paracrines—secreted into tissue fluids to affect nearby cells (eg. Eicosanoids described in previous chapters) Hormones—chemical messengers that travel in the bloodstream to other tissues and organs. Focus of this chapter © McGraw Hill 4 NERVOUS SYSTEM VS. ENDOCRINE SYSTEM 5 Keep in mind: Several chemicals function as both hormones and neurotransmitters: Eg. Norepinephrine, dopamine, and antidiuretic hormone Both systems can have similar effects on target cells: Eg. Both norepinephrine and glucagon cause glycogen hydrolysis in liver The two systems can regulate each other Eg. Neurotransmitters can affect glands, and hormones can affect neurons Neuroendocrine cells share characteristics with both systems Eg. Neuron-like cells that secrete oxytocin into blood 6  MAJOR ORGANS OF THE ENDOCRINE SYSTEM  Purely endocrine organs Pituitary gland Pineal gland Thyroid gland Parathyroid glands Adrenal glands  Endocrine cells in other organs Pancreas Thymus Gonads Hypothalamus 7  HORMONE RECEPTORS  Hormones stimulate only cells that have receptors for them; these are their target cells  The ability of a cell to respond to a hormone depends upon the presence of receptors for that hormone on or in the target cell  Target cells can adjust their sensitivity to a hormone by changing the number of receptors for it  An increase in the number of receptors for a hormone is called up-regulation  A decrease in the number of receptors for a hormone is called down-regulation 8  HORMONE RECEPTORS  Up-regulation Number of receptors is increased Sensitivity is increased  Down-regulation Reduced number of receptors Cell less sensitive to hormone Happens with long-term exposure to high hormone concentrations Bind to other receptors Converted to different hormone 9  HORMONE CLASSES Copyright © The McGraw-Hill Companies, Inc.  Three chemical classes of hormones  Steroids Derived from cholesterol Include sex steroids produced by the testes and ovaries (e.g. estrogens, progesterone and testosterone), and corticosteroids produced by the adrenal gland (e.g. cortisol, aldosterone)  Monoamines (biogenic amines) Derived from amino acids Include dopamine, epinephrine, norepinephrine, melatonin, and thyroid hormone  Peptides (and glycoproteins) Created from chains of amino acids Include oxytocin, antidiuretic hormone, insulin 10  HORMONE SECRETION BY GLANDS  Endocrine glands are the glands of the endocrine Copyright © The McGraw-Hill Companies, Inc. system Have secretory cells that secrete their products (hormones) directly into the bloodstream Contain dense, fenestrated capillary networks which allow easy uptake of hormones into bloodstream Once released into blood capillaries, hormones travel through blood vessels to reach their target cells (i.e. cells that have receptors for them) Endocrine gland Example: pituitary, thyroid, parathyroid, adrenal and pineal glands 11  CONTROL OF HORMONE SECRETION  Hormones aren’t secreted at steady state; they are usually secreted under the influence of stimuli that signify a need for them. Neural stimuli Nerve fibers supply some endocrine glands and elicit the release of their hormones (ex: the sympathetic nervous system stimulates the adrenal medulla to secrete epinephrine and norepinephrine) Hormonal stimuli Another hormone acting on the endocrine cell (ex: pituitary hormones stimulate other endocrine glands to release thyroid hormone, sex hormones, and cortisol) Humoral stimuli Changes in the plasma concentrations of mineral ions or organic nutrients (ex: rising blood glucose concentration stimulates the release of insulin) 12  CONTROL OF HORMONE SECRETION  NEURAL STIMULI Neurotransmitters released from neurons acting on the endocrine cell 13  CONTROL OF HORMONE SECRETION  HORMONAL STIMULI Another hormone (or paracrine/ autocrine agent) acting on the endocrine cell Ex: Hormones from the hypothalamus regulate hormone secretion by the anterior pituitary gland. The hormone secreted by the hypothalamus is called a tropic hormone since its target is another endocrine gland 14  CONTROL HORMONE SECRETION  HUMORAL STIMULI Change in plasma concentration of ions or nutrients A major function of the hormone is to regulate, through negative feedback, the plasma concentration of the ion or nutrient controlling its secretion 15  HORMONE TRANSPORT  To get from an endocrine cell to a target cell, a hormone must travel in the blood, which is mostly water  Most of the monoamines and peptides are hydrophilic; they can be mixed with blood plasma  Steroid hormones (and TH) are hydrophobic; they need to bind to hydrophilic transport proteins to travel in the watery bloodstream  A hormone attached to a transport protein is called a bound hormone, and one that is not attached is called an unbound (free) hormone 16  HORMONE TRANSPORT Copyright © The McGraw-Hill Companies, Inc.  Peptides and some monoamines (hydrophilic) travel in the plasma as unbound (free) hormones  Steroid and thyroid hormones (hydrophobic) travel in the plasma as protein-bound hormones 17  HORMONE TRANSPORT  Water-soluble (hydrophilic) hormones Most of the monoamines and peptides are water soluble Free hormones can circulate in the blood capillary for a short period of time (few minutes) They leave the blood capillary once they get to a target cell 18  HORMONE TRANSPORT  Lipid-soluble (hydrophobic) hormones Steroid and thyroid hormones are lipid- soluble They bind to a transport protein to travel into the blood capillary They will be protected from liver enzymes and kidney filtration. Hormones bound to a protein can circulate for a longer period of time in the bloodstream (hours to weeks) Only unbound hormone can leave a blood capillary and get to a target cell https://www.viddler.com/embed/49e9a56f/?f=1&autoplay=0&player=a rpeggio&secret=90576092&loop=0&nologo=0&hd=0 19  HORMONE INTERACTIONS  Most cells are sensitive to more than one hormone and exhibit interactive effects. There are 3 main types of interactive effects:  Synergistic effects Multiple hormones act together to produce a greater effect  Antagonistic effects One hormone opposes the action of another  Permissive effects One hormone enhances the target organ’s response to a second later hormone 20  HORMONE INTERACTIONS  Synergistic effects Also called additive effect Result is greater than the sum of individual effects Ex: Synergism between follicle-stimulating hormone and testosterone on sperm production  Antagonistic effects Also called opposing effect Net result depends on balance between hormones Ex: Insulin lowers blood glucose level and glucagon raises it © 2018 Pearson Education, Inc. 21  HORMONE INTERACTIONS  Permissive effects One hormone is needed for a second hormone to produce its effect Ex 1: Epinephrine releases fatty acids from adipose cells only in presence of thyroid hormones © 2018 Pearson Education, Inc. Hormone 1 must be present for the full effect of hormone 2. Binding of hormone 1 to its receptor upregulates the receptors for hormone 2, which can in turn bind to its receptor and exert its action. Copyright © The McGraw-Hill Companies, Inc. Ex 2: The effect of estrogen on the up-regulation of progesterone receptors in the uterus. 22  HORMONE CLEARANCE  Hormone signals, like nervous signals, must be turned off when they have served their purpose  Most hormones are taken up and degraded by the liver and kidney and then excreted in the bile or urine  Hormones can also be degraded by their target cells  Hormones that bind to transport proteins are removed from the blood much more slowly than free hormones  Metabolic clearance rate (MCR): This is the rate of hormone removal from the blood Half-life: time required to clear 50% of hormone from the blood The faster the MCR, the shorter the half-life 23  OUTLINE 1) OVERVIEW OF THE ENDOCRINE SYSTEM (HORMONES AND THEIR ACTIONS) 2) HYPOTHALAMUS AND PITUITARY GLAND 3) PINEAL GLAND AND THYMUS 4) THYROID, PARATHYROID, AND ADRENAL GLANDS 5) PANCREATIC ISLETS AND DIABETES 24  HYPOTHALAMUS AND PITUTARY GLAND  The hypothalamus and pituitary gland have the greatest influence on the endocrine system  Forms floor and walls of third ventricle of brain  The hypothalamus regulates primitive functions of the body ranging from water balance, energy homeostasis, goal-directed behaviors and thermoregulation  Most of its functions are closely associated with the pituitary gland (or hypophysis), which is suspended from the hypothalamus by a stalk—infundibulum 25  HYPOTHALAMUS AND PITUTARY GLAND  Primary capillaries in hypothalamus are connected to secondary capillaries in anterior pituitary (also called adenohypophysis) by portal venules (group of small vein), which are part of the hypophysial portal system.  Hypothalamic neurons secrete some hormones that are stored in the posterior pituitary (also called neurohypophysis) until released into the blood  The posterior pituitary is not a true gland (it’s a nerve tissue) It does not synthesize any hormones, it only secretes them 26  HYPOTHALAMUS AND PITUTARY GLAND  The two main posterior pituitary hormones are oxytocin and antidiuretic hormone They are synthesized in the hypothalamus, then transported to the posterior pituitary through a stalk (hypothalamo–hypophysial tract) and stored until their release  Oxytocin is involved in the milk ejection reflex of lactating mothers and in emotional bonding between partners  Antidiuretic hormone (vasopressin) helps increase water retention by the kidneys, reduces urine volume, and prevents dehydration 27  OXYTOCIN  Oxytocin enhances smooth muscle contraction in the wall of the uterus during childbirth and sexual intercourse  During childbirth, oxytocin helps the baby descend in the birth canal  During lactation, oxytocin induces uterine contractions that restore the uterus back to its pre-pregnancy size  After the child is born, oxytocin stimulates milk ejection (“let-down”) from mammary glands in response to the mechanical stimulus of suckling (breastfeeding) 28  ANTIDIURETIC HORMONE (ADH)  Also known as vasopressin  Has many important functions Decreases urine production in kidneys (cAMP upregulation, promoting then aquaporins expression, water retention) Decreases water loss by perspiration Increases blood pressure by promoting vasoconstriction (activates PLC, IP3 and Ca2+….)  Dehydration  Hypothalamic osmoreceptors detect a rise in blood osmolarity (low blood volume)→ADH released  Overhydration  ADH inhibited Note: ADH release is inhibited by alcohol and atrial natriuretic peptide (ANP, secreted by stretched right atrium due to increase in blood pressure) 29  PATHOPHYSIOLOGY OF ADH Hyposecretion of ADH (mostly congenital, or sometimes brain injury/tumor) causes Diabetes Insipidus Symptoms: polyuria (increased urination) and polydipsia (excessive thirst). Similar to the symptoms of diabetes mellitus. Treatment: constant water drinking or sniffing vasopressin through the nose. If not treated, results in dehydration, constipation, increase in blood osmolarity, muscle weakness, and permanent kidney damage. 30  CONTROL SYSTEMS INVOLVING THE HYPOTHALAMUS AND THE PITUITARY GLAND  Most hormones secreted by the hypothalamus follow this three- step sequence: (1) The hypothalamus secretes hormones that… (2) stimulate the anterior pituitary gland, which in turn secretes hormones that … (3) control the secretion of other hormones from some other endocrine glands 31 HYPOTHALAMUS/ANTERIOR PITUITARY HORMONES 32  FEEDBACK LOOPS  CRH-ACTH-cortisol sequence: Neural inputs include those related to stressful stimuli and non-stress inputs like circadian rhythms  Cortisol exerts a negative feedback by acting on: 1. Hypothalamus to inhibit CRH synthesis and secretion 2. Anterior pituitary to inhibit ACTH production CRH=corticotropin-releasing hormone ACTH=Adrenocorticotropic hormone 33  FEEDBACK LOOPS Short-loop and long-loop feedbacks  Short-loop feedback is exerted by an anterior pituitary hormone on the hypothalamus  Long-loop feedback on hypothalamus and/or anterior pituitary by the third hormone in the sequence 34  A Further Look at Growth Hormone (most other hormones are tropic hormones that will be described in other endocrine glands): -GH has widespread effects on the body tissues, especially cartilage, bone, muscle, and fat -Induces liver to produce growth stimulants: Insulin-like growth factors (eg.IGF-I): Stimulate target cells in diverse tissues IGF-I prolongs the action of GH Hormone half-life—the time required for 50% of the hormone to be cleared from the blood GH half-life: 6 to 20 minutes IGF-I half-life: about 20 hours © McGraw Hill 35  A Further Look at Growth Hormone Effects on target cells: Protein synthesis increases: boosts transcription and translation; increases amino acid uptake into cells; suppresses protein catabolism Lipid metabolism increases: stimulates adipocytes to catabolize fats (protein-sparing effect) Electrolyte balance: promotes Na+, K+, and Cl− retention by kidneys, enhances Ca2+ absorption in intestine; makes electrolytes available to growing tissues © McGraw Hill 36  A Further Look at Growth Hormone: Pathophysiology 1. Hypersecretion of growth hormone (GH) in adults causes acromegaly. 2. GH hypersecretion in childhood or adolescence causes gigantism. 3. GH hyposecretion in childhood or adolescence causes pituitary dwarfism. Pituitary dwarfism is rarer now that genetically engineered human GH is available. © McGraw Hill 37  OUTLINE 1) OVERVIEW OF THE ENDOCRINE SYSTEM (HORMONES AND THEIR ACTIONS) 2) HYPOTHALAMUS AND PITUITARY GLAND 3) PINEAL GLAND AND THYMUS 4) THYROID, PARATHYROID, AND ADRENAL GLANDS 5) PANCREATIC ISLETS AND DIABETES 38  THE PINEAL GLAND Pineal gland—attached to roof of the third ventricle beneath the posterior end of the corpus callosum After the age of 7, it undergoes involution (shrinkage) Declines 75% by the end of puberty May synchronize physiological functions with 24-hour circadian rhythms of daylight and darkness Synthesizes melatonin from serotonin during the night Pathophysiological states: Seasonal affective disorder (SAD) occurs in winter or northern climates. Symptoms: depression, sleepiness, irritability, and carbohydrate craving. Treatment: 2-3 hours of exposure to bright light each day reduces the melatonin levels and the symptoms (phototherapy) 39  THE THYMUS  The thymus plays a role in three systems: endocrine, lymphatic, and immune  It is a bilobed gland in the mediastinum, superior to the heart  It goes through involution after puberty  It is the site of maturation of T cells, which are important in immune defense  It secretes hormones (ex: thymopoietin, thymosin, and thymulin) that stimulate the development of other lymphatic organs and activity of T lymphocytes 40  OUTLINE 1) OVERVIEW OF THE ENDOCRINE SYSTEM (HORMONES AND THEIR ACTIONS) 2) HYPOTHALAMUS AND PITUITARY GLAND 3) PINEAL GLAND AND THYMUS 4) THYROID, PARATHYROID, AND ADRENAL GLANDS 5) PANCREATIC ISLETS AND DIABETES 41  THE THYROID GLAND  Largest adult gland to have a purely endocrine function Composed of two lobes and a narrow bridge of tissue, the isthmus, below the larynx Dark reddish brown color due to rich blood supply  Secretes thyroid hormone (TH) —90% T4 (four iodine atoms) and 10% T3 (three iodine atoms) Increases metabolic rate, O2 consumption, heat production (calorigenic effect), appetite, growth hormone secretion, alertness, quicker reflexes Increases respiratory rate, heart rate and strength of heartbeat to ensure adequate blood supply © The McGraw-Hill Companies, Inc. 42  THE THYROID GLAND  Thyroid follicles—structural and functional unit of the thyroid gland Contain follicular cells Simple cuboidal epithelium that lines follicles and secrete TH hormone. Epithelial cells produces thyroglobulin that can be iodinated and stored in the follicle. Upon stimulation, it is cleaved, forming triiodothryronine (T3) and tetraiodothyronine (T4), collectively known as TH which is released into the blood. T4 is more abundant, T3 is more active (BUT: when T4 enters cells it can be converted into © The McGraw-Hill Companies, Inc. T3). Also contain Parafollicular (C or clear) cells Secrete calcitonin with rising blood calcium Promote calcium deposition and bone formation 43  THE THYROID GLAND: Pathophysiology 1. Congenital hypothyroidism is hyposecretion of TH present from birth. 2. Severe or prolonged adult hypothyroidism can cause myxedema (weakness, fatigue, confusion, swelling, feeling cold). Both congenital and adult hypothyroidism can be treated with oral thyroid hormone. 3. A goiter is a pathological enlargement of the thyroid. Endemic goiter is due to a dietary deficiency of iodine, required for TH synthesis. Without TH, the pituitary produces extra TSH, and the thyroid gland undergoes hypertrophy. 4. Hyperthyroidism/Toxic goiter: Graves’ disease—autoantibodies mimic effect of TSH on the thyroid (bind and activate TSH receptor), causing thyroid hypersecretion, resulting in: anxiety, goiter, weight loss, bulging eyes, heart palpitations. 44  THE PARATHYROID GLANDS © The McGraw-Hill Companies, Inc.  The parathyroid glands usually consist of 4 glands partially embedded in the posterior surface of the thyroid gland About 5% of individuals have more than 4 parathyroid glands  Secrete parathyroid hormone (PTH) Increases blood Ca2+ levels by stimulating Ca absorption, bone resorption, synthesis of calcitriol (active form of Vit D) and reducing calcium losses in the urine Antagonizes the effect of calcitonin The parathyroid glands 45  THE PARATHYROID GLANDS © The McGraw-Hill Companies, Inc.  Parathyroid glands are separated from the thyroid follicles by a thin fibrous capsule and adipose tissue  If parathyroid glands are surgically removed, the individual can die because of impaired neuromuscular and cardiovascular function resulting from loss of calcium homeostasis 46 THE PARATHYROID GLAND: Pathophysiology Hypoparathyroidism (usually due to accidental removal of gland during thyroidectomy) causes a rapid decline in calcium levels, which can lead to a fatal, suffocating spasm of the larynx (hypocalcemic tetany) if not treated with hormone replacement. Hyperparathyroidism (usually results from a tumor) causes bone to become soft and fragile, and raises the blood levels of calcium and phosphate, promoting the formation of renal calculi (kidney stones) composed of calcium phosphate. 47  ADRENAL GLANDS © The McGraw-Hill Companies, Inc.  The adrenal glands lie on the superior side of the kidneys Located outside the peritoneal cavity, between the peritoneum and posterior body wall  Its inner core, the adrenal medulla, is 10% to 20% of the gland  The adrenal medulla is surrounded by an adrenal cortex The Adrenal Gland 48  ADRENAL GLANDS  Adrenal medulla Has dual nature acting as an endocrine gland and sympathetic ganglion of sympathetic nervous system When stimulated (fear or pain), it releases catecholamines (epinephrine and norepinephrine) and a trace of dopamine directly into the bloodstream Increases blood pressure, heart rate, blood flow to muscles, pulmonary airflow, and metabolic rate Decreases digestion and urine production 49  ADRENAL GLANDS  Adrenal cortex Surrounds adrenal medulla and produces more than 25 © The McGraw-Hill Companies, Inc. steroid hormones called corticosteroids or corticoids It forms three major layers a) Zona glomerulosa (thin, outer layer) Cells are arranged in rounded clusters Secretes mineralocorticoids (eg. aldosterone, part of the renin-aldosterone-angiotensin pathway)—regulates the body’s electrolyte balance (retain Na and water, excrete K) b) Zona fasciculata (thick, middle layer) Cells arranged in fascicles separated by capillaries Secretes glucocorticoids (mostly cortisol=hydrocortisone and some corticosterone)- promote fat and protein catabolism, gluconeogenesis, and mineralocorticoid receptors. In excessive amounts, can suppress immune system c) Zona reticularis (narrow, inner layer) Adrenal histology Cells in branching network Secretes sex steroids (androgens)-development of secondary sexual characteristics in puberty. 50  THE ADRENAL GLAND: Pathophysiology 1. Cushing syndrome is excess cortisol secretion due to any of several causes, including ACTH hypersecretion by the pituitary, ACTH-secreting tumors, or hyperactivity of the adrenal cortex. 2. Cushing syndrome disrupts carbohydrate and protein metabolism, leading to hyperglycemia, hypertension, muscle weakness, and edema. a. Muscle and bone mass are lost as protein is catabolized. b. Abnormal fat deposition between the shoulders or in the face may also occur. Note: These may also be effects of long-term hydrocortisone therapy. 51  OUTLINE 1) OVERVIEW OF THE ENDOCRINE SYSTEM (HORMONES AND THEIR ACTIONS) 2) HYPOTHALAMUS AND PITUITARY GLAND 3) PINEAL GLAND AND THYMUS 4) THYROID, PARATHYROID, AND ADRENAL GLANDS 5) PANCREATIC ISLETS AND DIABETES 52  THE PANCREATIC ISLETS  Pancreatic islets are endocrine cell © The McGraw-Hill Companies, Inc. clusters scattered throughout the pancreas  The pancreas itself is an elongated exocrine digestive gland located behind the stomach  Pancreatic islets are also called islets of Langerhans They are primarily made of Alpha (α) cells, Beta (β) cells, and Delta (δ) cells Also contain F cells that secrete pancreatic polypeptide Pancreas-gross anatomy and cellular composition 53  THE PANCREATIC ISLETS  Alpha (α) cells Also called glucagon cells Secrete glucagon between meals when blood glucose concentration is falling In liver, glucagon stimulates glycogenolysis (breakdown of glycogen into glucose) and gluconeogenesis (synthesis of glucose from fats and proteins) In adipose tissue, glucagon stimulates fat catabolism and release of free fatty acids Light micrograph of pancreatic islet Glucagon is also secreted in response to rising amino acid levels in blood (promote uptake of amino acids into cells to provide raw material for gluconeogenesis) 54  THE PANCREATIC ISLETS  Beta (β) cells Also called insulin cells Secrete insulin during and after a meal when blood glucose and amino acid levels are rising Insulin stimulates cells to absorb glucose and amino acid and to store or metabolize them It thus lowers blood glucose and amino acid levels Insufficiency or inaction of insulin is the primary cause of diabetes mellitus Light micrograph of pancreatic islet  Delta (δ) cells Also called somatostatin cells Secrete somatostatin (GH-inhibiting hormone), which helps regulate the speed of digestion and nutrient absorption 55  Pathophysiology: DIABETES MELLITUS  Most prevalent metabolic disease in the world Disruption of metabolism due to hyposecretion or inaction of insulin Symptoms include: Polyuria, polydipsia, and polyphagia (ravenous hunger).  Physiologically: Hyperglycemia (in blood) and high amounts of ketones in the blood causing ketoacidosis, which can eventually lead to diabetic coma and death. Presence of glucose and ketones in the urine (glycosuria and ketonuria). Ketonuria flushes Na+ and K+ from the body, creating electrolyte deficiencies. Hyperglycemia causes damage to small blood vessels in eye (blindness), kidneys (renal failure) and heart (atherosclerosis). Diabetic neuropathy is nerve damage resulting from impoverished blood flow. This can lead to loss of sensation, poor wound healing, incontinence, and erectile dysfunction.  Two predominant forms: Type 1 diabetes mellitus (5-10% of the cases) Type 2 diabetes mellitus (90-95% of the cases) 56  DIABETES MELLITUS  Type 1—5% to 10% of cases Due to hyposecretion of insulin Autoantibodies attack and destroy pancreatic beta cells Insulin is always used to treat type 1 Insulin injections, insulin pump, or a dry insulin inhaler can be used It is important to monitor blood glucose levels and maintain a controlled diet  Type 2—90% to 95% of diabetics Characterized by insulin resistance Failure of target cells to respond to insulin Risk factors are heredity, age (40+), obesity, and ethnicity (Native American, Hispanic, and Asian) Can be managed through a weight-loss program of diet and exercise Often supplemented with glycemia-lowering oral medications such as metformin 57 The End 58