197 terms

Endo test 2

pituitary gland aka
Pars nervosa
major part of neural tissue
Anterior pit (pars tuberalis, pars distalis, pars intermedia)
posterior pit (pars nervosa, infundibulum)
Pars distalis
major part of adenohypophysis
Downgrowth from neurohypophysis
Raphe's pouch
roof of mouth -- turns into adeno
Alpha melanocyte stimulating hormone (alpha MSH)
in pars intermedia
alternate name: Adrenocorticotropic hormone (ACTH)
Hormone synthesizing cells
suffix: tropes; ex: gonadotropes (synthesize LH, TSH)
Acidophilic cells
stain with acid dyes (GH, PRL cells)
stain with basic dyes (TSH, FSH, LH, ACTH)
Show little staining (ACTH)
Category 1 hormones (GH, PRL)
similar size (191/199); common AA
GH fxns
stimulate growth, extracellular deposition of bones, lipases that convert triglycerides to FFAs and body fat
Somatomedin hypothesis
says GH actions are mediated by somatomedins produced in liver and other tissue; Ex: insulin like growth factors (IGF)
GH secretion
highest during sleep, hypothalamic control, hypoglycemia stimulus released
GH related dz
Dwarfism (underproduction); Gigantism (excess GH, linear bone growth); Acromegaly (excess GH in adults)
Tx for GH deficiency
Genotropsin ex of hGH, excess GH long acting analogs of SST
PRL fxns
diverse in vertebrates (reproduction, growth and development, water/electrolyte balance, integument (skin, hair feathers)
Effects of PRL on reproduction
mammary gland developmt and secretion in mammals; luteotropic effect in rodents; crop milk production in birds (brood patch development)
PRL secretion
inc during sleep/pregnancy; stimulated by nursing; inhibited by dopamine
Category 2 horm's (FSH, LH, TSH)
double chained w/ 2 subunits (alpha and beta; alpha same w/i spp, B determines hormone specificity)
FSH fxns
F (stimulate development of ovarian follicles) M (stimulate synthesis of androgen binding protein in sertolli cells, formation of LH receptors in Leydig cells)
LH fxns
F (stimulates ovulation, corpus luteum formation, estrogen synthesis) M (stimulates T synthesis by Leydig cells)
TSH fxns
stimulates thyroid gland
Category 3 horm's (ACTH, aMSH, BLPH)
derived from pro-opiomelanocortin (POMC)
ACTH fxn
stimulates glucocorticoid synthesis in adrenal cortex
aMSH fxn
affects pigmentation via cation of malanophores
BLPH fxn
stimulates lipolysis in fat cells, source of endorphins such as B endorphins
panhypopituitarism - total loss of secretion
Neoplastic tumor of hormone producing cells, most common in microadenonas
Parvocellular neurosecreatory neurons of hypothalamus
small size, in many hyponuclei, produce hypophysiotropic hormones that regulate the anterior pituitary fxn, axons extend to the primary plexus of median eminence
Hypophysiotropic horms
regulate activity of endocrine cells of hypophysis
Neurovascular hypothesis
hormonal rather than direct neural control of AP gland; Geoffrey Harris supporter;
Exceptions to NV hypothesis
increase amount of hormone released: Prolactin (synthesis and release inhibited by dopamine), aMSH (controlled by dopamine)
Evidence for NV hypothesis
interruption of vascular system altered horm secretion; reciprocal transplantation of pit gland between M and F rats indicated that hypothalamus controls AP fxn (not gender specific)
Hypophysiotropic neurohormones
neurohorms produced by neurosecratory neurons of hypothalamus that regulate release of AP horms
Guillemin and Schally
Discovered sxr of hypophysiotropic horms: (pyro) glu his pro nh2 -- correct sxr of TRH
TRH fxns
stimulate release of TSH in homeotherms (mammals/birds); useful to test ability of pituitary to produce TSH
GnRH fxn (gonadotropin RH)
decapeptide; fxns to release FSH,LH; neuroregulation of GnRH: dopaminergic neurons stimulate secretion, encephalinergic neurons inhibit secretion
Clinical importance GnRH
induce ovulation; treat oligospermia, constant exposure causes gonadotrope desensitization; GnRH longacting analogs = antifertility agent
Somatostatin SST
produced by neurosecratory cells in hypothalamus: inhibits GH release from AP; Produced by G cells of GI tract and pancreatic islets: inhibits gastrin release, inhibits insulin/glucagon release; Long acting analogs treat acromegaly, PUD, diabetic retinopathy s/p DM
stimulates GH release from AP
stimulates GH release from AP; produced in stomach, sm intestine, hypothalamic neurosecreatory neurons; regulates feeding behavior/energy homeostasis
CRH - Corticotropin releasing horm
stimulates ACTH release; stress stimulates CRH release; cholinergic pathways important, atropine can block pathways
neurotransmitter; inhibits prolactin release; agonists inhibit PRL release from AP, antagonists stimulate release; Hyperprolactinemia in 28% women with menstrual abnormalities, treat with dopamine agonists (parlodel, bromocryptine mesylate)
MSH release inhibiting hormone
dopamine inhibits MSH release, dopamine present in hypo portal system
Feedback control of pituitary horm excretion
Cortisol (neg feedback) Thyroxine, Estradiol/testosterone
Negative feedback
Hypothalamus releases CRH to AP, stimulates ACTH release
Autoinhibition/short loop feedback
inhibitory effects of release of ACTH
Long loop feedback
ACTH target, adrenal cortex releases cortisol (negative feedback at higher level: hypothalamus)
Neurohemal organ
axon endings, vascular bed, pituicytes
collection of nerve cell bodies in CNS; supraoptic and paraventricular (more oxytocin)
Magnocellular neurosecratory neurons
paraventricular nucleus, supraoptic nucleus, preoptic nucleus (PON)
Sxr of neurohypophysial hormones
nonapeptides, 12 different ones, 2 different horms in a spp (exceptions: cyclostomes, lamprey and hagfish -- only have arginine vasotocin)
Transport of neurohypophysial horms
via larger proteins called neurophysins: Vasopressin neurophysin = pressophysin, oxytocin NP = oxyphysin, cleaved off during axonal transport, secreted with neurohormones
OT (oxytocin) release
neuroendocrine reflex - result of sensory input to SC -> brain; neuron depolarization in AP of pars nervosa -> Ca entry -> exocytosis of OT; AP reach axon tips in 0.5-1.5m/s; ex of stimulus released coupling: rapid response
Fxns of neurohypophysial horms
osmoregulate, contractile regulation (vasopressin-osmo, OT -contractile activity: uterine, milk release, orgasm); Vasopressin - antidiuretic, ADH, increase permeability of collecting ducts to water
Mechanism of vasopressin
80% h2o uptake in proximal tubule by AVP independent means, other 20% by horms (AVP acting on collecting ducts, aldosterone acting on distal tubes)
Factors affecting AVP release: plasma osmolality
<280 = little/no release, >280 = increase release; release very sensitive to change; osmoreceoptors in anterior hypothalamus detect changes in blood Na
Factors affecting AVP release: blood volume/pressure
AVP less sensitive than response to changes in osmolality, 5% dec in BP, 8% dec in BV; important with hemorrhage and blood loss, location of arterial baroreceptors: aortic arch, carotid sinus, lt atrium
Factors affecting AVP release: Angiotensin II
component of rennin angiotensin system, acts on brain to stimulate AVP release
Inhibiting factors of AVP
atrial natruiuretic factor (ANF), ethanol, low temp
Arginine Vasotocin (AVT)
key neurohypophysial hormone, constricts preglomular arterioles in birds/reptiles, increase h2o permeability in the skin of frogs and urinary bladder of toads
Neurohypophysial contractile activity
pregnancy (OT release causes contraction during labor); mammary glands (OT causes milk release); mating (inc uterine activity, orgasm, milk ejection, inc sperm transport)
OT causes embryonic diapuse of kangaroos
suckling: OT release; OT inhibits P synthesis by corpus luteum or ovary -> development of blastocyte; AVT mediates egg laying in sea turtles
Neurohypophysial hormones and BP
OT causes umbilical arteries to contract; AVP causes contraction in some peripheral vascular beds: mediated via the V receptor, IP3 causes inc in intracellular Ca
Diabetes insipidus
Excess water loss in urine, inc volume of urine, hypernatremia, high plasma osmolality; 2 types (pituitary/neurogenic: failure to produce/release AVP, nephrogenic/AVP resistant) Ex: Brattleboror rat doesnt produe AVP due to mutuation
Syndrome of inappropriate vasopressin secretion
Continual AVP release independent of plasma osmolality; sxs: dec urine volume, hyponatremia, hypoosmality
aMSH from larger precursor; Peptides from pro-opiomelanocortin (POMC), heptapeptide sequence conserved
aMSH cleared from ACTH sections of POMC
Pars distalis (corticotrophs) -> ACTH; Pars intermedia (melanotrophs) ->ACTH and enzymes to break down ACTH to aMSH --> aMSH and CLIP
Pars intermedia
source of melanotropins; present in cyclostomes, amph, reptile and most mammals (well defined pars intermedia or lobe wtih MSH secreting cells); not present in birds, whales/dolphins, adult humans (present in fetus)
pigment containing cells, present in all vertebrates, prominent in poikilotherms (dont use metabolism to regulate temp); fxns: camo, warning signals, sexual states, thermoreg, protection from solar radiation; ex: veiled chamelion
Melanin pigment; eumelanins (black/brown) and pehomelanins (yellow/red); pig's in melanostomes (fully melanized organelle); located in dermis/epidermis
yellow/orange/red pigments; carotenoids/pteridines; located in dermis
Iridescent pigment: reflects light, contains crytal purines; located in dermis
Physiological color change
rapid(min), pigment aggregates/disperses, typical of poikiotherms; change color with background; Affected by aMSH (MSH absent: light skin, MSH present: skin dark)
Dermal chromatophore unit
integrated functional units; important in rapid color change in amphibians and reptiles (ex: green anole lizard, brown vs green)
aMSH present
MSH binds to melanocortin1 receptor; inc in cAMP dec "free" Ca2+ causing relaxation of melanofilaments which allow melanosomes to spread, causing skin to darken
aMSH absent
dec in cAMP increase free Ca2+ causing contraction of melanofilaments whic hpull melanosomes into smaller area, causing lightened skin
Morphological color change
slow (days/weeks), inc pigment/# pigment cells, involves epidermal melanophores, aMSH stimulates melanin sythesis and/or inc number of melanophores
Epidermal melanin unit
consists of melanocyte and epidermal cell; impt in human skin/hair color, aMSH in humans not controlling amt of pigment produced usually, aMSH does play a role in other mammals
fur color in mammals; ex: short tailed weasel, white fur in winter (inc aMSH), brown fur in summer (dec aMSH)
MSH stimulation of melanin sythesis
tyrosinase improtant in formmation of DOPA which is basic structure leading ot melanin
Neuro control of aMSH
inhibition (Dop hyperpolarizes aMSH secreting cells and inhibits MSH release) stimulation (Acetylcholine depolarizes MSH secreting cells and stimulates MSH release)
Color change with background
High albeto, inc reflectance, dec MSH, lighter skin; low albeto, dec reflectance, inc MSH, dark skin::: inc survival in dft environments
Neuroendocrine reflex regulating pigment dispersion
dark backgroun -> inhibit dopamine, inc MSH, dark skin; light backgroun, CNS stimulates dopamine, dec MSH, light background ::: track from retina through brain
Adrenal gland
human (MSH causes development of fetal zone prior to birht, ACTH causes development of cortex after birth) sheep (switch from MSH to ACTH increasing cortisol sythesis, which induces birth of lamb)
Food intake and MSH
aMSH binding to melanocortin4 reduces food intake (inc leptin, inc MSH); inhibition of Mc4r causes overeating and obesity (Agouti protein inhibits Mc4r)
Serum Ca
about 10mg/ml; free Ca biologically active; low Ca causes tetany (twitches)
Factors affecting serum Ca balance
GI absorption; storage in bone as Ca10(PO4)6(OH)2 (80% Ca in bone); relationship to P: [Ca] x [PO4] = K; PO4 stored in bone/tissue not carefully regulated
Hormones regulating Ca
Parathyroid (PTH), Calcitonin (CT), 1a,25dihydroxyvitamin D3 [1,25(OH)2D3] = VitD = calcitrol
PTH - parathyroid horm
polypeptide essential for life; fxns to inc blood CA levels, produced by chief cells of parathyroid gland;
Regulation of PTH release
low Ca2+ stimulates, high Ca2+ inhibits, 1,25(OH)2D3 inhibits PTH synthesis
Important bone cells
osteoblasts (new bone formation); osteoclasts (bone breakdown, 18% Ca in bone now replaced in one year)
PTH action on bone
increase Ca mobilization from bone; stimulate osteoblasts to release osteoclast diff inducing factore (IL-6) that cause osteoclasts to release acid proteases whichd digest bone matrix; stimulates differentiation of precursor cells to osteoclasts
PTH action on kidneys
inc tubular reabsorption of Ca into ascending loop of Henle; inc excretion of PO4, inhibits H+ secretion into tubules; inhibits bicarb reabsorption
PTH action on intestine
acts indirectly to inc CA2+ and PO4 uptake by activating 1a-hydroxylate enzyme required to form 1a,25(OH)2D3
PTH related peptide (PTHrp)
hypercalcemic agent produced by tumors, nl physio fxns in growth and development (inc fetal serum Ca, tooth eruption, mammary gland development)
Calcitonin (CT)
dec blood Ca by acting on bone to inhibit osteoclast activity; produced by C cells (parafollicular cells that arise from ultimobranchial glands in mammals, migrate to thyroid gland) located in thyroid gland
Regulation of CT release
Inc Ca stimulates release; gastrin stimulates release
Physiological fxns
prevent hypercalcemia after meals; mineralization of bone in pre-weaning young; protect against Ca loss in pregnancy, lactation and prolonged Ca deprivation
Vitamin D3/D2
Prehormones for 1,25(OH)2D3; Vit D3 (cholecalciferol) synthesized in skin from 7-dehydrocholesterol upon exposure to UVB, also in animal tissue; Ergocalciferol (D2) from plants can be used to form 1,25(OH)2D3
biologically active horm affecting Ca, synthesized from Vit D3, Vit D3 from diet/skin exposed to UV light
Formation of Vit D3
7-dehydrocholesterol: from liver to skin: is converted to Vit D3, enters blood, binds to protein, adds hydroxyl groups
Synthesis of 1,25(OH)2D3
Vit D3 binds to transcalciferin in blood, goes to liver with 25,hydroxylate forming 25(OH)Vit D3; blood moves to kidneys and reacts wtih 1a-hydroxylate stimulated by PTH, forming active 1,25(OH)2D3
Fxs of 1,25(OH)2D3
Intesting (stimulate sythesis of Ca-binding protein, inc # Ca channels) :: Kidney (inc Ca reabsorption) :: Bone (accretion of new bone during remodeling) :: PT gland ( inhibits PTH synthesis)
Feedback control of 1,25(OH)2D3
synthesis requiring sunlight; active hormone to gut causes + action of Ca and PO4; bone/kidney inc effects of reabsorption Ca/PO4; Ca to O high -> neg feedback, inhibits release from PTH
Binding of 1,25(OH)2D3 to HSPs
Can form heterodimers, ect
dec in release of PTH; causes tetany and convulsions; tapping facial muscles detects latent tetany; pseudohypoparathyroidism - nl PTH levels, low Ca levels, failure to generate cAMP
dec bone density due to demineralization; postmenopausal (type 1) -- dec steroid hormone; senile (type 2) - lack of Vit D :: spinal osteoporosis - loss of mineralization, compression of vertebrae
Failures in nl bone mineralization
rickets (failure in kids) osteomalacia (in adults) Paget's dz ( weak bones due to excessive osteoclasts)
Therapies for Ca loss dz
CT tx; Biphosphonates (fosamax, boniva, actonel); selective estrogen recetpor modulator (SERMS); topical Vit D; lifestyle modifications (weight bearing exercise/ Ca uptake)
Fxn of GI hormones in digestive movements
enzye, acid/base secretion; smooth muscle contraction; horm release from pancreatic islets; growth promoting actions
Location of GI horms
distributed diffusely; clear cells tained by silver or chromium salts; termed: argyphil cells, argentaffin cells, enterochromaaffic cells, or enterochromaffin like cells(ECL); GI and pacreatic horms = gastroenteropancreatic horms
Gastrin family
gastrin (G) and cholecystokinin (CCK); share same 5AA at carboxyl end
CCK and G receptors
CCK-A in pancreas acinar cells, CCK-B in brain and stomach, G receptor similar to CCk-B
Mech of gastrin
CCK & G inc IP3 which inc free Ca2+, evolved from a CCk ancestral molecule :: fish/amph only have CCk, reptiles/birds/mammals have CCK and G
Secretin family
Secretin, glucagon, gastric inhibitory peptide (GIP), vasoactive intestinal peptide (VIP); share AA sequences; inc cAMP
Gastrin release
food (peptides, AA, IFA), distention of stomach, activity of vagus nerve (GRP) inhibited by SST
Gastrin fxns
Primarily to increase HCL (release of H+ from stomach parietal cells) directly and indirectly (via stimulataing HCL cells to release histamine that stimulates the parietal cells via H2 receptors); inc calcitonin release and gastric mucosal growth
Cholecystokinin (CCK)
Produced by I cells of duodenum; stimulus for release: HCL, AA, FAs
CCK fxns
gallbladder contractions, relaxation of sphincter of oddi, inhibition of gastric emptying, inc pancreatic enzyme secretion and bicarb secretion, stimulates growth exocrine pancreas
CCK and feeding
inhibits feeding behavior; bulemic people release les CCk than nl people; anorexia of aging inc sensitivity to CCK and dec feeding
S cells of dueodenum synthesize them; acid stimulates release (not release when pH >4.5)p; inc bicarb secretion from pancreas
GIP - gastric inhibitory peptide
aka glucose-dependent insulinotropic peptide, enterogastrone; made in K cells, small intestine; stimulus for release are fats and glucose
Fxn of GIP
insulin release in response to glucose; inhibits gastric acid secretion; anabolic action on adipose cells (FFA to triglycerides);
Glucagon like peptide-1 (GLP-1)
intestinal peptide encoded in proglucagon gene; produced by L cells of the intestine; stimulates insulin release in presence of glucose and suppresses glucagon secretion
Vasoactive Intestinal peptide (VIP)
in neurons of CNS and ANS; has vasodilator and hypotensive effects; mediates descending relaxation component of peristaltic reflex
most originate in pancreatic islets and secrete insulin, glucagon, sometimes gastrin and VIP; Gastrin secreting tumor (gastinoma) -> Zollinger-ellison syndrome (ulcers); VIP secreting tumor (vipoma) -> pancreatic cholera (watery diarrhea); CCK in required for gallbladder fxn, pentagastrin for gastric acid secretion
Cells and hormones of islets of Langerhans
B cells (insulin) a cells (glucagon) D cells (SST) F cells (PP, pancreatic polypeptide)
Distribution of cells
B cells surrounded by a cells and SST secreting cells; blood flow from B to a cells, gap junctions
Glucose homeostasis
Flux in and out of blood in a controlling point; balance of glucose production and utilization; hormone regulators: insulin, glucagon, cortisol, epi, GH; improtant tissues that regulate glucose; liver, adipose tissue, muscle
hypoglycemic hormone that dec BSG levels, inc m/m of glucose into cells
hyperglycemic horm that inc BSG levels, inc glucose m/m into blood, dec storage/utilization of glucose in cells :: Cortisol, GI, Epi also hypoglycemic hormones
insulin stimulates, glucagon inhibits; fuel source: diet; glycogenesis, lipogenesis, protein sythesis
insulin inhibits, glucagon stimulates; fuel source: storage depots; glycogenolysis, lipolysis, proteolysis
Glucose preduction from noncarb carbon substrates: AA from proteins, glycerol from fats
Glucose sparing
using substances other than blucose to generate energy: FFA from fats
Amino acids
glucogenic AA can be converted to carbs: alanin and glutamine most impt, leucine and lysine cant be used
Alanine transamination
Converts alanine to pyruvic acid which produces glucose (gluconeogenesis) and acetyl CoA (glucose sparing)
Broken down by lipases to glycerol and FFA; Glycerol converted to glucose by gluconeogenesis, FFA converted to acetyl CoA by glucose sparing
Ketone bodies
Acetone, Acetoacetic acid, B-hydroxybutyric acid
Insulin sxr
2 chains (A chain, 21AA, B chain, 30 AA), 2 inter-chain disulphide bridges
Insulin metabolism
Haptic blutathione insulin dehydrogenase (liver) separates A and B chains; half life is about 5 min
Insulin action
RK activated receptor phosphorylates tyrosines of proteins; Glucose transporter systems;
insulin insensitive, in the liver and pancreas, bi-directional transport, direction depends on glucose concentration
insulin sensitive; in skeletal and cardiac muscle, adipose tissue; insulin causes 20-40 fold inc in glucose transport rate; 80% of insulin mediated glucose uptake in skeletal muscle
Effects of insulin on liver
increase glucose uptake indirectly by stimulating glucokinase which inhibits glucose-6 phosphate; inc glucose storage by stimulating glucose sythetase; inc lipid sythesis by stimulating triglyceride sythetase
Effects of insulin on adipose cells
inc glucose uptake and use, glycerol synthesis, FFA uptake (via stimulating lipoprotein lipase in endothelial cells); dec lipolysis in fat cells via inhibiting lipases
Effects of insulin on muscle
inc glucose uptake via GLUT-4, glucose storage in glycogen, AA uptake and protein sythesis
Factors stimulating insulin release
Hyperglycemia, AA, FFA, ketone bodies, glucagon, acetylcholine (vagal nerve), gastric inhibitory peptide (GIP), glucagon like peptide-1 (GLP-1)
Insulinotropic hormones (Incretins)
inc insulin release from B cells in response to glucose; Januvia is an oral antihyperglycemic drug that inhibits GLP-1
Oral insulins`
Sulfonylureas (ex: carbutamide, tolbutamid) close K+ ATP channels whic open Ca2+ channels; free Ca 2+ stimulates insulin release form B cells
Factors that inhibit insulin release
Hypoglycemia; epi via blood; Norepi in sympathetic nerves; SST
Effects of glucagon on liver
inc in glucose release, gluconeogenesis, glycogenolysis, ketogenesis:: dec in glycogenesis
Glucagon effects on fat cells after long term hypoglycemia
inc breakdown of tri,di,monoglycerides forming FFA and glycerol; simulates hormone dependent lipases
Factors stimulating glucagon release
hypoglycemia; AA (arginine and alanine blocked by glucose); Epi, norepi
Factors inhibiting glucagon release
Hyperglycemia, Insulin, SST
Effects of arginine infusion
insulin/glucagon increase; glucose only slightly elevated; problems with all protein meal -> hypoglycemia:: AA causes insulin release which causes dec in BSG, but glucagon inc prevents hypoglycemia
Sxs as early as 1500 BC; leading cause of death after heart dz, CA, AIDS; most common endocrine disorder
Juvenile onset, insulin dependent; lack of insulin; requires insulin replacement; 20% of cases, most serious; 90% childhood cases; mortality 10x nl
Medical problems w/ type 1 DM
uremia, renal failure, MI, CVA, blindness, gangrene, PVD, impotence (loss of small vessel/nerves), failure of wounds to heal, tissue damage from hyperglycemia
Prolonged hypoglycemia damage
glycosylation of proteins, formation of sorbitol from glucose
Problem with protein glycosylation
excess glucose in blood binds to proteins, glycosylated proteins accumulate in eye membranes, kidneys, nerves, vascular system and other organs, inhibi nl fxn
Problem with sorbitol formation
Excess BSG accumulates in cells of peripheral nerves and ocular lens; excess BSG converts to sorbitol; sorbitol and product fructose cause edema in cells; edema of fine vessels/nerves: diabetic retinopathy
DM 1 may be autoimmune
antibodies invade islets,d estroy B cells; antibody formation mayb e triggered by virus; genetic contribution
Type 2 DM
Maturity onset, non insulin; most common; insulin level may be low nl or high; insulin normally not required to tx but may facilitate management
Metabolic sydrome, associated with DM2
High fasting BSG; High triglyceride levels; low blood high density lipoprotein (HDL); HTN
Obesity vs DM2
90% of pts, most can lose weight to control; location of fat is impt: upper body worse M>40" F>35"
polypeptide horm released by B cells at smae time as insulin; dec BSG by inhibiting glucagon induced hepatic glucose release, inhibits gastric emptying, appetite and food intake; DM2 less amylin released than nl; Symilin synthetic analog of amylin, improves glycemic control
Causes of DM2
relatively unknown, multiple possible causes in theory
Visceral fat more important
more highly associated with metabolic syndrome, releases adipokines: hormones that regulate energy and glucose homeostasis
induce insulin resistance: Resistin (proinflammatory, TZD's) IL-6 (proinflammatory, inc with obesity and DM) TNF-a (proinflammatory cytokine,r elease by visceral fat more than subcutaneous)
increase insulin sensitivity; levles inversely related to body fat; acts wtih insulin to inc glucose uptake and metabolism in muscle and block glucose formation in liver; decreased in DM2
inc BSG, cellular starvation in some tissues/muscle; inc glycosylated hgb in blood (HbAlc levels) (>7% glucose not controlled)
glucose exceeds tubular max, excess remain in urine
excess urine; glucose acts as diuretic; Na slats of ketone bodies also diuretics; leased to hemoconcentration, circulation failure, oliguria
Inc thirst due to dehydration
Inc eating duet o cellular starvation
inc ketones in blood (acetone breath); dec pH leads to metabolic acidosis causing come and death
Electrolyte depletion
Inc K+ in urine
gluconeogenesis leads to inc FFA and glycerol; dec VLDK clearance due to dec lipoprotein lipase activity (requires insulin)
Muscle wasting
emaciation from muscle breakdown; use of gluconeogenic AAs for energy
Tx of DM 1
insulin replacement; monitor BSG levels; B cell transplant; insertion fo insulin gene in other cell types
In vivo reprogramming of adult pancreatic exocrine cells to B cells
3 transcription factors incude insulin cells in adult mouse pancreas in vivo; induced new B cells originate from differentiated exocrine cells; endogenous and induced B cells re indistinguishable in morphology and ultrastructure; incuded new B cells remodel vascularature adn amliorate hyperglycemia; STZ destroys B cells
Tx of DM 2
diet, exercise, drugs to overcome insulin resistance
Regulation of hunger
Ghrelin (stimulates ) and Obestatin (suppresses); ratio important; precursor molecule has opposite effect
protein released from stomach; levels rise before meals; experiment with rodents showed that ones treated wtih horm ate more and gained weight; humans treated at 30% more at a buffet
Leptin (greek for thin)
released from adipose cells; gene termed -ob for obese
Leptin levels regulate 2 key populations of neurons in hypothalamic arculate nucleus
neurons that make a-MSH (inhibit feeding) and neurons that make neuropeptideY (NPY) which directly stimulated appetite and Agouti related protein (AGRP) which stimulates feeding
Large fat cells
produce more leptin to eat less
Small fat cells
produce less leptin to eat more
High leptin levels from large fat cells due to eating too much
stimulate a-MSH release which binds to melanocortin-4 receptor, decreases appetitie/eating
Eating too little effect
smaller fat cells decrease leptin which increases NPY release that binds to NPY receptor and increases AGRP (MC4R agonist) which both increase appetite and eating
endogenous cannabinoid receptor; agonists that stimulate appetite; Leptin inhibits anandamide induced feeding