Pathophys Flashcards
Benefits of Exercise
Increased insulin sensitivity, reduction in BP, improved lipids, reduction in inflammation in synovial fluid, and increased lean muscle mass
FAST TWITCH (muscle fibers)
Type II - Energy from short term glycolysis, creates forceful contractions, suited for short-term sprint activities requiring forceful muscle contraction
SLOW TWITCH (muscle fibers)
Type 1 - abundant mitochondria, energy from oxidative metabolism, fatigue resistant, suited for prolonged PA, slow contraction and increased oxidation (SO)
GLP-1
Glucagon-Like Peptide 1 - produced in L cells and secreted in response to food (c, p, f); Glucose-dependent insulin secretion, suppresses glucagon, delayed gastric emptying and increased satiety, reduced appetite
*GLP-1 levels increase significantly after bypassing the proximal small intestine thus DM improves immediately after gastric bypass
CCK
Cholecystokinin - produced in i cells and secreted in response to fat and protein ingestion, short acting; slows gastric emptying, reduces appetite
Small Intestine Hormones (ANOrexic)
CCK, GLP, OXM, PYY
Factors that Reduce Ghrelin
Meals (Carbs suppresses fast, but rebounds fast; protein suppresses longer), Weight gain, Leptin, Gastric sleeve surgery
Factors that Increase Ghrelin
Fasting/prolonged fasting, Weight Loss, Stress/Sleep deprivation, Genetics/syndromes (i.e. Prader Willi)
OREXigenic Pathway (Hunger)
Ghrelin ==> NPY/AgRP in the CNS (also may reach brain from vagal nerve and nucleus tractus solitarius) ==> increase food intake and weight gain
Ghrelin
Growth Hormone RELease Inducing Peptide - only circulating OREXigenic gut hormone = hunger
Orexin A/Orexin B
Orexigenic - found in 2nd order neurons in lateral hypothalamus, stimulated by NPY and AgRP, increased arousal
MCH
Melanin Concentrating Hormone - orexigenic; 2nd order neurons in lateral hypothalamus, stimulated by NPY/AgRP; increases food intake, acts on higher order neurons to stimulate cognitive function for feeding, pleasure reward; inhibited by leptin
AgRP
Agouti-related Peptide - orexigenic, found in arcuate nucleus, with NPY, stimulated by ghrelin, inhibits MC3R, MC4R; inhibited by insulin, leptin, PYY, and serotonin; decreases energy expenditure, oxygen consumption
NPY
Neuropeptide Y; orexigenic, in arcuate nucleus, found with AgRP; most abundant central neuropeptide and most potent orexigen; stimulated by ghrelin, inhibited by insulin, leptin, PP, PYY, and serotonin
Anorexigens - reduce intake
Propiomelanocortin (POMC), Cocaine amphetamine regulating transcript (CART), a-melanocyte stimulating hormone (a-MSH), Brain derived neurotrophic factor (BDNF), Serotonin
Orexigens (increase intake)
Neuropeptide Y (NPY), Agouti-related protein (AgRP), Orexin-A, Orexin-B, Melanin-concentrating hormone
Second Order Neuron
Deeper in the hypothalamus; receive signals from the 1st order neurons and relay to other parts of the brain; NPY acts on Y1 and Y5 receptors while AgRP blocks MC4R; POMC ==> a-MSH ==> MC4R
First order neurons
Receive signals from the periphery to the arcuate nucleus (AN); 2 neuron systems: NPY/AgRP (weight gaining); POMC/CART (weight losing)
Adiponectin
Made only in white adipose tissue; most abundantly secreted; inversely related to body fat mass (higher body fat = lower adiponectin); enhances insulin sensitivity in the liver, stimulates glucose use in the muscle, and reduces vascular endothelium inflammation
Orexigenic (Gain weight)
Gold Star: Ghrelin; acute appetite stimulatory hormone, increase energy balance, Stomach, Acts on Hypothalamus and vagal nerve
Ghrelin ==> NPY, AgRP, Orexin; ==} POMC, CRH
Anorexigenic (reduce weight)
Gold star: Leptin - long term energy balance; decreased energy balance, release from adipocytes and acts on hypothalamus
Leptin ==> POMC, CART, CRH; ==} NPY, AgRP, Orexin
Leptin Resistance
Increased levels of leptin higher than anticipated for body fat mass, but do NOT cause the anticipated anorexic weight loss effects; could be related to over-stimulation of the leptin receptor may cause, impairment of leptin crossing the blood brain barrier (BBB) which inhibits the effectiveness of leptin signaling
Brown Adipose Tissue
Heat production, abundant mitochondria, dense nerve supply, high-volume capillaries, UCP1, decreases with age, women>men, and young>old
White Adipose Tissue
Energy storage, mostly made of triglycerides, Leptin, increase with age relative to total body weight
Leptin
Anorexigenic, secreted ONLY by white adipose tissue, long term signaling, metabolic signal of energy sufficiency, levels are directly proportional to body fat mass, reduced food intake, increased energy expenditure, crosses BBB, stimulates POMC/CART (1st order) and inhibits NPY/AgRP (1st order), Turns off GABA inhibition of POMC (1st order), Inibits Orexin (2nd order), Stimulates neurotrophic factor (2nd order)
Adipocyte Hormones
Leptin, Adiponectin, Inflammatory Cytokines (IL6, TNF, etc)
What is the largest endocrine gland in the body?
Adipose (body fat)
Amylin
Robin to insulin’s batman, co-secreted with insulin, reduces food intake, slow down gastric emptying, suppresses glucagon production, similar to GLP-1; helps make insulin more effective for glucose lowering
Glucagon
Secreted by alpha cells, stimulated by low glucose; inhibited by high glucose, GLP-1, amylin; acts on liver and stimulates gluconeogenesis, maintains blood sugar levels between meals
Insulin
secreted by beta cells, 1 of 2 long term adiposity signaling hormones (with leptin), centrally reduces appetite, uptake of glucose into glycogen, stimulates fat synthesis
Pancreatic Polypeptide (PP)
Secreted by F cells, reduces gastric emptying, reducing hunger, obesity and prader willi are associated with low levels of PP
Pancreatic Hormones
Pancreatic polypeptide (F cells), Insulin (Beta), Amylin (Beta), Glucagon (alpha cells)
PYY
Peptide YY - produced in L cells of distal small bowel, colon and rectum, potent appetite suppression, delays gastric emptying; ileal brake with GLP-1
OXM
Oxyntomodulin - produced in L cells, distal small bowel, co-secreted with GLP-1, unique to increase energy expenditure
GLP-1
Glucagon-Like Peptide 1 - produced in L cells and secreted in response to food (c, p, f); Glucose-dependent insulin secretion, suppresses glucagon, delayed gastric emptying and increased satiety, reduced appetite
*GLP-1 levels increase significantly after bypassing the proximal small intestine thus DM improves immediately after gastric bypass
Glucagon
Secreted by alpha cells, stimulated by low glucose; inhibited by high glucose, GLP-1, amylin; acts on liver and stimulates gluconeogenesis, maintains blood sugar levels between meals
POMC
Propiomelanocortin - anorexigenic, 1st order neuros in ARC, found with CART, releases a-MSH which acts on MC3R and MC4R, stimulated by serotonin, leptin, and insulin, inhibited by NPY and GABA
Orexigenic pathway
NPY/AgRP ==> Neuropeptide Y ==> Y1, Y5
Anorexigenic Pathway
POMC/CART ==> a-MSH ==> MC3R, MC4R
CART
Cocaine and Amphetamine Regulated Transcript (CART) - anorexigenic, found with POMC, located in ARC or lateral hypothalamus, may involve central release of GLP-1, stimulated by serotonin, leptin, and insulin, inhibited by NPY and GABA
Brown Adipose Tissue
Heat production, abundant mitochondria, dense nerve supply, high-volume capillaries, UCP1, decreases with age, women>men, and young>old
