ENDOCRINE SYSTEM

Dr.REISNA REFIANA

Comparison of Nervous and Endocrine Systems Nervous

messenger

Endocrine
hormone (chemical)

electrochemical

response duration

milliseconds short-lived

seconds to days long-lived

system (several widely scattered distribution one subsystems)

NOTE: Nervous and endocrine systems work together to coordinate and integrate activities of body (homeostasis)

Functions of Endocrine System

1. Reproduction

2. Growth and development

3. Response to stress 4. Maintenance of fluid (water), electrolyte and nutrient balance 5. Regulation of cellular metabolism and energy

Organs of the Endocrine System

1. Pituitary gland 2. Hypothalamus (neuroendocrine) 3. Pineal gland 4. Thyroid gland 5. Parathyroid gland 6. Thymus gland 7. Adrenal gland 8. Pancreas (also has exocrine function) 9. Gonads (testes or ovaries - also have exocrine functions)

 Hormone Types Modes of Action Target cell activation Control

Topics

Specific glands, their hormones, and disorders Pituitary Thyroid Parathyroid Adrenal Pancreas Thymus Gonads (testes and ovaries) General Adaptation Syndrome

Hormones
chemicals secreted by endocrine gland cells into blood (by way of interstitial fluid) regulate metabolic functions of other cells (called target cells) carried to all cells, but action is specific to cells that have receptors for the hormone specificity of bodys response to hormone depends on how many cells have the receptor (highly specific if few cells respond [e.g., ACTH]; diffuse action if many respond [e.g., thyroxine])

Chemical Types of Hormones

Amino-acid based (amino acids, short or long peptides, proteins) e.g., insulin, growth hormone, prolactin Steroids - lipid derivatives of cholesterol e.g., hormones from gonads (testosterone, estrogen) e.g., hormones from adrenal cortex (adrenocortical hormones) Eicosanoids - locally-secreted, locally-acting hormones secreted by all cell membranes (e.g., prostaglandins, which increase blood pressure and contribute to uterine contraction)

Types of Changes in Target Cells

plasma membrane permeability changes (opening of protein channels; may change membrane potential) activation of genes for increased protein synthesis, including enzymes activation or deactivation of enzymes already present secretion of cellular products stimulation of cell division (mitosis)

Mechanisms of Action
action in target cell depends on receptor receptor may be: in plasma membrane second messenger mechanisms used by most amino acid-based hormones (water soluble) intracellular (in cytoplasm or nucleus) direct gene activation used by steroids and thyroid hormones (lipid soluble)

Mechanisms of Action: Steroids

bind to intracellular receptors hormone diffuses through plasma membrane and makes its way to nucleus > where it binds with intracellular receptor to form hormone-receptor complex > hormone-receptor complex interacts with chromatin (DNA) to affect gene activity (turn genes on or off) > synthesis of mRNA > synthesis of protein

Steroid Signaling

Mechanism of Action: Thyroid Hormone

similar to mechanism for steroid hormones

diffuses across plasma membrane

diffuses into nucleus where it interacts with intracellular receptors to activate genes for proteins (enzymes) involved in cellular respiration (glycolysis) also, binds to receptors at mitochondria to activate genes for proteins involved in cellular respiration (Krebs cycle and electron transport chain)

Mechanisms of Action: Other Hormones

* plasma membrane receptor used by most amino acid-based hormones interaction of hormone with plasma membrane receptor results in activation of second messenger systems (cyclic AMP or PIP-calcium) activation of second messenger has cascade effect resulting in: enzyme activation, or membrane permeability changes or secretion

Membrane Receptor Mechanisms: 1. Cyclic AMP (cAMP) Signaling

interaction of hormone with receptor > activates G protein (cleaves phosphate from GTP)-> excitation > G protein activates adenylate cyclase > adenylate cyclase forms cAMP from ATP > cAMP activates protein kinases > protein kinases activate (or inhibit) other proteins by phosphorylation > cAMP degraded by enzyme slightly different G protein inactivates adenylate cyclase - associated with different hormone receptor

Link to animation: http://student.ccbc.cc.md.us/c_anatomy/animat/cAMP.ht

cAMP Signaling Mechanism

Membrane Receptor Mechanisms: 2. PIP-Calcium Signaling interaction of hormone with receptor --> activates membrane-bound enzyme phospholipase > phospholipase cleaves PIP2 (phosphatidyl inositol diphosphate) into diacylglycerol (DAG) and IP3 -- each of which acts as a second messenger diacylglycerol (DAG) activates protein kinases IP3 (inositol triphosphate) causes release of Ca2+ into cytoplasm (from endoplasmic reticulum or other storage areas) --> Ca2+ acts as third messenger

PIP-Calcium Mechanism (cont)

-> Ca2+ (third messenger)

changes enzyme activity and plasma

membrane channels, or binds to calmodulin (intracellular regulatory protein) --> activates enzymes

PIP-Calcium Signaling Mechanism

Factors Affecting Target Cell Activation

a. blood levels of hormone, which depend on: rate of hormone release rate of deactivation (by target cell or liver) b. affinity of hormone for receptor greater affinity means greater association -> greater effect c. number of receptors available

Factors Affecting Target Cell Activation

(cont)

c. number of receptors available up-regulation: increase in blood level of specific hormone (normally present at low levels) causes cells to make more receptors down-regulation: prolonged exposure to high level of specific hormone --> cells remove some receptors -->return to normal response level cross-regulation: influence of one hormone on number of receptors for another hormone; e.g., progesterone causes uterus to make fewer estrogen receptors; estrogen causes uterus to make more progesterone receptors

Hormone Removal
hormones may be: degraded by specific enzymes within target cells; removed from blood by kidneys (excreted in urine) degraded by liver (excreted in urine and feces) half-life - time for 1/2 of hormone to be removed (from

a fraction of a minute to 30 minutes)

onset - time from release to action (minutes [amino acid-based] to days [steroids]) duration of action - how long the effects last (~20 minutes to several hours)

Control of Hormone Release

Humoral control
Neural control

Hormonal control

Control of Hormone Release: Humoral

Hormone released in response to changing blood levels of ion or nutrient (negative feedback)
parathyroid glands: detects low blood Ca2+ PTH raises blood Ca2

thyroid (parafollicular cells) detect high blood Ca2+-->calcitonin->decrease blood Ca2+

Control of Hormone Release: Humoral

Other examples: pancreas: beta cells detect high blood glucose insulin decreases blood glucose alpha cells detect low blood glucose glucagon raises blood glucose zona glomerulosa (of adrenal cortex) detects low blood Na+ or high blood K+ aldosteronetthy, K+

Control of Hormone Release: Neural

Hormone released in response to nerve impulse
preganglionic fibers of sympathetic division stimulate release of catecholamines (epinephrine, norepinephrine) from adrenal medulla impulses from hypothalamus result in release of oxytocin or ADH from posterior pituitary

Control of Hormone Release: Hormonal

Hormone produced by one endocrine gland (or hypothalamus) affects secretion of hormone by another endocrine gland hypothalamus acts as overall coordinator releases regulatory hormones (releasing hormones or inhibitory hormones) affects anterior pituitary anterior pituitary, when stimulated, secretes hormones that affect other glands (e.g., TSH [thyroid stimulating hormone] stimulates release of thyroid hormones from thyroid gland)

Hormonal Control: Role of Hypothalamus

Releasing hormones from hypothalamus stimulate secretion from anterior pituitary Inhibitory hormones from hypothalamus inhibit secretion by anterior pituitary Impulses from hypothalamus cause release of hormones from posterior pituitary

Hormone Control - Misc.

nervous system can override normal endocrine control e.g., in fight-or-flight response, sympathetic impulses result in release of epinephrine and

norepinephrine

from

adrenal

medulla

-->

increases blood glucose levels to maintain fuel supply during stress or exertion (overrules effect of insulin on blood glucose level)

Organs of the Endocrine System and Their Products

The following major glands will be covered one at a time with their products: 1. Pituitary gland / Hypothalamus 2. Thyroid gland 3. Parathyroid gland 4. Adrenal gland 5. Pancreas (also has
exocrine function)

6. Gonadal hormones
(ovaries and testes)

7. Thymus

1. Pituitary Gland (Hypophysis)

located in sella turcica of sphenoid bone (in cranial cavity), inferior to hypothalamus consists of two lobes: A. neurohypophysis (~ posterior pituitary) attached to hypothalamus by infundibulum contains axons and axon terminals of neurosecretory cells whose cell bodies are in hypothalamic nuclei B. adenohypophysis (~ anterior pituitary) consists of glandular epithelium

http://www.usc.edu/hsc/dental/ghisto/end/c_1.html

Pituitary Development

From roof of mouth

http://calloso.med.mun.ca/~tsc ott/head/pit.htm

A. Neurohypophysis (Posterior Pituitary)

consists of nerve fibers (axons of neurosecretory cells with cell bodies in hypothalamus) and

pituicytes (glial cells that support nerve fibers)

acts primarily as a storage and releasing area for hormones actually made in hypothalamic nuclei hormones released in response to impulses from hypothalamus (neural control)

hormones are short amino acid chains (peptides)

oxytocin antidiuretic hormone (ADH or vasopressin)

A. Neurohypophysis : Oxytocin (OT)

action, in pregnant or nursing women:

stimulates contraction of smooth muscle of

uterine wall during labor and delivery stimulates ejection of milk in lactating mothers action, in men and non-pregnant women, may be involved in sexual arousal and orgasm

A. Neurohypophysis : Oxytocin (OT)

control:

during labor/delivery, positive feedback:

stretching of uterus/cervix --> sensory impulses to hypothalamus --> increased

secretion of OT --> increased contraction

suckling: sucking of infant on breast --> sensory to hypothalamus --> oxytocin release --> release of milk

A. Neurohypophysis: Antidiuretic Hormone (ADH)

action: antidiuretic hormone (ADH) directly

affects blood pressure - acts as powerful

vasoconstrictor --> increases blood pressure (hence name vasopressin) * action: affects water balance (indirect affect on blood pressure) - acts on tubules of kidney

to increase reabsorption of water less

water lost in urine

A. Neurohypophysis: ADH
disorders: hyposecretion due to damage of hypothalamic nucleus or neurohypophysis-> diabetes insipidus - excessive urine

production (polyuria) and thirst

hypersecretion --> SIADH (syndrome of inappropriate ADH secretion) - water retention, headache, cerebral edema, weight gain, hypoosmolarity

Antidiuretic Hormone (ADH): Control

neural control: increased electrolyte (NaCl) concentration --> affects (supraoptic) nucleus in hypothalamus --> impulse to neurohypophysis --> release of ADH --> increased water reabsorption --> decrease in electrolyte concentration other stimuli: pain, low BP, morphine, barbiturates, nicotine, aldosterone (hormone from adrenal cortex - hormonal control) inhibition: alcohol (results in more urine production and, potentially, dehydration) diuretic drugs - some act to supress ADH secretion; used to treat hypertension and congestive heart failure

B. Adenohypophysis (Anterior Pituitary)

linked to hypothalamus via hypophyseal portal system (capillary networks and small veins) carries regulatory hormones from hypothalamus to pituitary releasing hormones stimulate secretion of pituitary hormones inhibitory hormones inhibit secretion consists of epithelial cells all hormones produced are proteins * tropic hormones - affect some endocrine glands or provide maintenance oversight for other organs

B. Adenohypophysis : Growth Hormone (GH)

highest levels during evening and sleep action: stimulates increased rate of protein synthesis leading to cell growth and division bones and skeletal muscle respond more than other body cells action: stimulates use of fat as energy source and decreases rate of glucose uptake and glucose metabolism (diabetogenic effect spares glucose) control: release stimulated by GHRH (growth hormone releasing hormone) from hypothalamus inhibited by GHIH (from hypothalamus) and somatomedins (produced by liver under GH stimulation)

Growth Hormone (GH): Disorders

Disorders: hypersecretion gigantism (in children) up to 8 tall, normal body proportions acromegaly (after epiphyseal plates close) enlargement of extremities and face, thickening of soft tissue hyposecretion pituitary dwarfism - in children, up to 4 tall progeria - premature aging, atrophy of body tissues

B. Adenohypophysis: Prolactin (PRL)

action: * stimulates milk production in mammary glands; helps stimulate development of mammary glands (along with other hormones); in males, may help regulate testosterone production control: stimulation: PRH (prolactin-releasing hormone from hypothalamus), high estrogens, breast-feeding inhibition: PIH (hypothalamus), stimulated by rising PRL levels, low estrogen

B. Adenohypophysis : Prolactin (PRL)

Disorders hyperprolactinemia = hypersecretion due to adenohypophyseal tumors; results in

galactorrhea, lack of menses and infertility in

women, impotence in men

B. Adenohypophysis: Thyroid-Stimulating Hormone (TSH)

TSH = thyrotropin action: stimulates secretion of hormones from thyroid gland (T4 and T3); also stimulates development of thyroid in youth control: release stimulated by TRH (thyroid releasing hormone from hypothalamus) inhibited by rising levels of thyroid hormones and by GHIH

B. Adenohypophysis: Adrenocorticotropic hormone (ACTH)

ACTH=corticotropin action: stimulates release of hormones from adrenal cortex control: release stimulated by CRH (corticotropinreleasing hormone from hypothalamus)

release inhibited by rising levels of

glucocorticoids from adrenal cortex

B. Adenohypophysis: Gonadotropins
regulate activity and secretion by gonads (testes in males; ovaries in females) control: stimulated by GnRH (gonadotropinreleasing hormone from hypothalamus) release of GnRH is inhibited by rising levels of estrogens, progestins and androgens (testosterone) two important hormones FSH LH

Gonadotropins: Follicle-Stimulating Hormone (FSH)

action: females (ovaries) - stimulates development of ovarian follicles and estrogen production males (testes) - stimulates sperm production and development inhibited by inhibin and testosterone from testes (feedback to hypothalamus and anterior pituitary) and estrogen, progesterone and inhibin from ovaries (feedback to anterior pituitary)

Gonadotropins: Luteinizing Hormone (LH)

LH=lutropin action: females (ovaries) - induces ovulation; stimulates secretion of estrogens and progestins (e.g., progesterone) males (testes) - stimulates production of androgens (e.g., testosterone ) inhibited by estrogen, progesterone and inhibin form ovaries (feedback to anterior pituitary) and by inhibin and testosterone from testes (feedback to hypothalamus and anterior pituitary)

2. Thyroid Gland
located anteriorly in cervical region, just inferior to thyroid cartilage; two lobes connected by thin isthmus largest purely endocrine gland in body consists of follicles (cuboidal or simple squamous epithelium) filled with colloid (combination of protein [thyroglobulin] containing amino acid tyrosine [building block of thyroid hormones]) parafollicular cells produce calcitonin

http://www.usc.edu/hsc/dental/ghisto/end/c_26.html

2. Thyroid Gland: T4 and T3

hormones based on amino acid tyrosine (differ in number of iodine ions) thyroxine (tetraiodothyronine [T4]) and triiodothyronine (T3) T3 is 10x more active, but less common (T4 accounts for about 90% of all thyroid hormone) much T4 converted to T3 by liver, kidneys, some other tissues

2. Thyroid Gland: T4 and T3

affect metabolic rate of every cell in the body, except brain, spleen, testes, uterus and thyroid gland affect other activities within these organs

and glands
readily cross membranes (diffuse through plasma membrane to bind to mitochondrial receptors and receptors in nucleus)

2. Thyroid Gland

T4 and T3:

Actions

increase synthesis of enzymes involved in cellular respiration --> increase basal metabolic rate increases glucose oxidation --> ATP synthesis increases ATP synthesis in cytoplasm and by mitochondria results in increased heat production (calorigenic effect) work with GH to promote normal tissue growth and development, especially important to growth/development of CNS, skeletal and reproductive systems

T4 and T3: Control

release stimulated by TSH (thyroid-

stimulating hormone from adenohypophysis)

release of TSH stimulated by TRH from hypothalamus

release of TRH is stimulated by cold,

pregnancy, low thyroxine

release inhibited by GHIH, high glucocorticoid levels, high sex hormone levels, high iodine

Hypothyroidism
too little thyroid hormone (thyroid gland defect, inadequate TSH, TRH, or iodine) Hashimotos thyroid autoimmune disorder in which

thyroid is attacked and function decreases

myxedema - low BMR, constipation, puffy eyes, edema, lethargy, mental sluggishness endemic goiter - enlargement of thyroid gland usually due to lack of sufficient iodine cretinism - genetic deficiency of thyroid gland or lack of dietary iodine during development resulting in mental

retardation, disproportionate growth, short body with

thick tongue and neck treatment - reversed by iodine supplements or hormone replacement therapy

Hyperthyroidism
too much thyroid hormone (thyrotoxicosis) Graves disease - autoimmune disease in which abnormal antibodies similar to TSH mimic its function and continuously stimulate release of thyroid hormones; results in high BMR, sweating, rapid heart rate, weight loss, restlessness, mood shifts, fatigues easily, limited energy; also toxic goiter exophthalmos - protrusion of eyeballs, fibrous tissue become edematous (swollen) treatments - removal of thyroid gland or irradiation patient must be on synthetic thyroid hormone the rest of his/her life

2. Thyroid Gland: Calcitonin (CT)

polypeptide produced by parafollicular cells actions: decreases blood calcium levels by: stimulating osteoblasts (Ca2+ uptake and incorporation into bone) inhibiting osteoclast activities (osteoclasts break down bone matrix releasing calcium) control: responds directly to blood calcium levels very rapid effect probably more important during childhood when it stimulates bone growth important because at high blood Ca2+, membranes become less permeable to Na+

3. Parathyroid Glands
2 paired structures on posterior of thyroid gland oxyphyil cells - function unknown chief cells secrete parathyroid hormone (PTH; protein) actions: increases blood Ca2+ by: stimulating osteoclast activity (which break down bone matrix) while inhibiting osteoblasts (which form bone matrix) stimulating increased reabsorption of Ca2+ by kidney indirectly stimulating increased absorption of Ca2+ by small intestine by causing secretion of calcitrol form kidneys

3. Parathyroid Glands

Hyperparathyroidism
rare; caused by parathyroid gland tumor

results in hypercalcemia (excess Ca2+

levels in blood) --> depression of nervous

system (because of effect on sodium

permeability), abnormal reflexes, skeletal muscle weakness, nausea, vomiting, kidney stones, calcium deposits in soft tissues; bones become soft

Hypoparathyroidism
trauma to or removal of parathyroid

gland
results in hypocalcemia (low blood

Ca2+) --> neurons become too excitable

--> muscle tetany --> spasms/cramps -

-> respiratory paralysis --> death

4. Adrenal Glands
located in abdominal cavity against back wall (retroperitoneal), superior to kidney surrounded by connective tissue capsule two regions: cortex - outer region, glandular, three zones zona glomerulosa - outer zone zona fasciculata - middle zone zona reticularis - inner zone medulla - inner region, modified neural tissue (develops from same tissue in embryo as ganglionic [postganglionic] neurons of sympathetic division)

4. Adrenal Gland Development

http://sprojects.mmi.mcgill.ca/embryology/ug/Adrenal_Stuff/Normal/zones.html

4. Adrenal Gland: Regions and Zones

Adrenal Cortex: Zona Glomerulosa

produces steroid hormones based on cholesterol mineralocorticoids - ion (and water) balance main hormone is aldosterone action: * stimulates reabsorption of Na+ and secretion of K+ from kidney, sweat glands, salivary glands, pancreas secondarily, increases water reabsorption in kidney (water follows Na+)

Adrenal Cortex: Zona Glomerulosa

control: aldosterone release stimulated by: high K+, low Na+ angiotensin II (result of renin-angiotensin pathway stimulated by low blood pressure), ACTH (when under severe stress) inhibited by low K+, high Na+

Adrenal Cortex: Zona Glomerulosa

Disorders: aldosteronism = hypersecretion (adrenal tumor) increased water and Na+ reabsorption --> hypertension, edema; loss of K+ --> disruption of neural and muscle function

Adrenal Cortex: Zona Glomerulosa

Disorders: Addisons Disease = hyposecretion glucocorticoids and mineralocorticoids results in decreased Na+ and water reabsorption, increased blood K+ --> low blood volume --> hypotension, dehydration; changes in membrane potentials --> disruption in neural and muscular function also decreased cortisol secretion by zona fasciculata --> decreased blood glucose levels (especially during prolonged stress)

Adrenal Cortex: Zona Fasciculata

glucocorticoids - effects on glucose metabolism main hormone is cortisol (hydrocortisone) actions: maintains blood glucose levels, especially in times of stress, by: promoting gluconeogenesis (making new glucose in liver) and use of alternative fuels by other cells (saves glucose for the brain) anti-inflammatory decrease immune response * can be used clinically to treat allergic reactions (e.g., poison ivy), rheumatoid arthritis

Adrenal Cortex: Zona Fasciculata

Control stimulated by ACTH

inhibited by cortisol (inhibits secretion of CRH

from hypothalamus) blood levels peak in the morning Disorders: Addisons Disease

- hyposecretion of glucocorticoids and

mineralocorticoids

Zona Fasciculata: Cushings Disease

hypersecretion of glucocorticoids caused by hypersecretion of ACTH due to tumor in ZF, pituitary, lungs, kidneys, or pancreas suppresses glucose metabolism resulting in hyperglycemia (elevated glucose= steroid diabetes), stimulates lipid metabolism (weight loss), loss of muscle and bone mass, buffalo neck and moon face (fat redistribution), anti-inflammatory effects (mask infection) water and salt retention (effect of aldosterone hypersecretion --> water retention --> hypertension)

Adrenal Cortex: Zona Reticularis

gonadocorticoids most are androgens (male sex hormones) -

converted to testosterone; small amounts of

estrogens actions: may contribute to onset of puberty (levels rise between 7 and 13 years of age; exact function compared to hormones from ovaries or testes

unclear)
control: stimulated by ACTH

Adrenal Cortex: Zona Reticularis

hypersecretion results in: masculinization and masculine pattern of hair distribution in females in males - rapid maturation of reproductive

organs, secondary sex characteristics;

hypersecretion of estrogens causes feminization and gynecomastia (enlarged breasts)

Adrenal Medulla
chromaffin cells (modified neurons - arise from same embryonic tissue as postganglionic neurons of sympathetic division) catecholamines - epinephrine (~80%), norepi

(NE)
control: secretion stimulated by preganglionic fibers of sympathetic nerves during flight-orfight response

Adrenal Medulla
actions: epinephrine (more potent) - increases HR (beta receptors), bronchodilation (in lungs), increased blood glucose (breakdown of

glycogen in liver and skeletal muscle, and

breakdown of adipose tissue) NE - peripheral vasoconstriction --> increased BP

5. Pancreas
has both exocrine (acini secrete digestive enzymes) and endocrine function (islets of Langerhans) control: responds to blood glucose levels (humoral) hormones are polypeptides (proteins)

5. Pancreas
major cell types alpha cells secrete glucagon

beta cells secrete insulin

delta cells secrete somatostatin (which inhibits insulin and glucagon secretion, and decrease fat absorption in intestines) F cells regulate exocrine function of pancreas

(secrete pancreatic polypeptide)

5. Pancreas: Glucagon actions: hyperglycemic (increases blood glucose) stimulates formation and release of glucose from liver (main target) glycogenolysis - breakdown of glycogen (storage form of glucose) gluconeogenesis - formation of glucose from noncarbohydrate molecules (e.g., amino acids, glycerol, lactic acid) stimulates glycogenolysis in skeletal muscle stimulates triglyceride breakdown in adipose tissue (fat mobilization)

5. Pancreas: Glucagon
control:

secreted in response to low blood sugar,

rising amino acid levels in blood inhibited by increased blood glucose and by somatostatin

5. Pancreas: Insulin actions: hypoglycemic (lowers blood glucose) increases transport of glucose into muscle and fat cells (NOTE: does not increase uptake by brain, liver, or kidney) inhibits breakdown of glycogen and formation of glucose from amino acids or fatty acids (inhibits glycogenolysis and gluconeogenesis) promotes formation of glycogen (liver, skeletal muscles), protein synthesis (muscle), and fat synthesis and storage (adipose)

5. Pancreas: Insulin (Control)

stimulated by: increased blood glucose increased blood amino acid and fatty acid levels parasympathetic impulses hyperglycemic hormones (GH, glucagon, epinephrine, thyroxine, glucocorticoids) indirectly result in insulin secretion by increasing blood glucose levels inhibited by: low blood glucose and by somatostatin sympathetic impulses

5. Pancreas: Insulin - Disorders: Diabetes Mellitus (DM)

hyposecretion (or hypoactivity) of insulin body cells not stimulated to take up glucose hyperglycemia (excess blood glucose) very high glucose --> nausea --> fight-or-flight response --> secretion of hyperglycemic hormones (epi, NE [adrenal medulla], glucocorticoids [adrenal cortex]) --> stimulates gluconeogenesis, lipolysis, glycogenolysis --> adds to already high glucose not all sugar reabsorbed from urine --> glucose lost in urine (glucosuria) --> increased water loss -> excessive urine production (polyuria) and excessive thirst (polydipsia)

Insulin Action on Cells: Dominates in Fed State Metabolism

5. Pancreas: Insulin - Diabetes Mellitus

cells use fats as energy source (due to poor glucose uptake) hyperglycemic hormones stimulate fat mobilization --> fats in blood (lipidemia) --> increase in lipid metabolites in blood (ketone bodies, which are strong organic acids) --> decrease blood pH (ketoacidosis) and ketone bodies in urine (ketonuria) decreased blood pH --> severe depression of nervous system --> deep breathing --> diabetic coma --> death polyphagia (excessive hunger) - final sign, due to use of fats and proteins as energy sources

Type I Diabetes mellitus

also called insulin-dependent diabetes (IDDM; formerly juvenile onset diabetes) onset is sudden, usually before age 15 may be due to autoimmune attack of proteins in beta cells (see A Closer Look, p. 640641) result is lack of insulin activity lipidemia (high blood lipid content) and increased cholesterol lead to long-term vascular problems (arteriosclerosis, strokes, heart attacks, renal shutdown, gangrene, blindness) treated with insulin injections or pancreatic islet transplant (newer technique)

Diabetes Mellitus: Abnormally Elevated Blood Glucose (Hyperglycemia)

Type II Diabetes Mellitus

non-insulin-dependent (NIDDM; formerly mature-onset diabetes) usually starts after age 40 insulin levels are normal or elevated, but peripheral tissue become less sensitive to it 25-30% of Americans carry gene that predisposes them to NIDDM, more likely in over-weight people (~90% of cases) adipose cells secrete tumor necrosis factor alpha that depresses production of protein needed for glucose uptake often controllable with diet and exercise

Hyperinsulinism
excess of insulin (usually from injection of excess) causes hypoglycemia --> secretion of hyperglycemic hormones (to raise blood glucose) - low glucose to brain --> anxiety, nervousness, tremors, weakness --> eventually, disorientation, convulsions, death due to insulin shock treated by providing sugar source