Chapter 9 - Gastrointestinal Physiology and Regulation of Substrate Metabolism

Question 1

Inflammatory Bowel Disease

Answer 1

In children, leads to retarded growth and delayed puberty

Question 2

Sphincters in GI Tract

Answer 2

Mouth –> Esophagus - Upper esophageal sphincter
Esophagus –> Stomach - Lower esophageal sphincter
Stomach –> Duodenum (small intestine) - Pyloric Sphincter
Ileum –> Cecum - Ileocacal Valve
Rectum –> Exterior - External and Internal Anal Sphincters

Question 3

Digestive Organs and Functions

Answer 3

Liver, gall bladder and pancreas are digestive organs attached to GI tract for producing bile, digestive enzymes, and bicarbonate for digestion

Liver - synthesizes bile and releases it to gall bladder for storage (bile functions as detergent for breaking up fat into small micelles for digestion)

Gall Bladder - stores bile

Pancreas - secretes digestive enzymes and bicarbonate into the duodenum of the small intestine for digestion of carbohydrates, proteins, and fats

Question 4

Blood Flow through GI Tract

Answer 4

Abdominal Aorta –> Mesenteric Arteries –> GI Tract –> Hepatic Portal Vein –> Liver

All substances absorbed by GI tract must pass through liver before going into general circulation, liver is major organ for drug metabolism (oral drugs must go through “first-pass” of liver, can reduce availability of drug in general circulation)

Question 5

Blood flow through Liver

Answer 5

Hepatic Portal Vein and Hepatic Artery –> Liver –> Hepatic Central Vein

In addition to portal vein from GI tract, liver also gets blood from hepatic artery (coming from abdominal aorta) - blood from portal vein and hepatic artery enters sinusoids lined by hepatocytes and leaves the sinusoids via the central vein which drains into the inferior vena cava

Question 6

Portal Triad

Answer 6

The hepatic artery, portal vein, and bile duct - arranged together in the same location in the liver

Question 7

Swallowing and Swallowing Reflex

Answer 7

Control of swallowing center is in brain stem and swallowing reflex regulates the closing of the entry to the trachea and the opening of the upper esophageal sphincter for the entry of food from mouth into esophagus (trachea and esophagus share the oral-nasal cavity for the passage of air and food)

Swallowing is initiated by voluntary movement of food bolus toward the back of the oral cavity where it triggers sensory input to the swallowing center (and higher centers of the cerebral cortex also send input to swallowing center)

The swallowing center executes a pattern generator program that:

1. Sends inhibitory signals to the respiratory center to inhibit respiration
2. Sends excitatory signals to muscle groups in larynx-pharynx region to cause downward tilting of the epiglottis to cover the airways
3. Sends inhibitory signals to the upper esophageal sphincter to induce relaxation of the sphincter, allowing the entry of the food bolus into the esophagus (and the stomach also relaxes for reception)

Question 8

The Peristaltic Reflex in General

Answer 8

Propels food and digestive products along the GI tract (from oral –> anal)

Does this by local enteric neurons (under modulation of central and enteric nervous system) causing contraction of GI tract behind bolus and relaxation of tract in front of bolus

Uses skeletal and smooth muscle contractions (because the upper third of the esophagus contains skeletal muscle and the lower two-thirds contain smooth muscle cells)

Peristalsis in skeletal muscle region is regulated by coordinated sequential activation of motor neurons by swallowing center

In the smooth muscle region there is voluntarily initiated (primary) and involuntarily initiated (secondary) peristalsis

Primary peristalsis - sequential activation of smooth muscle cells by parasympathetic nervous system

Secondary peristalsis - regulated by enteric nervous system under the modulation of hormones and ANS, pacemaker cells in the GI generate slow waves of depolarization that propagate along the GI tract and set the basic rhythms of peristalsis by periodically bringing the membrane potential of smooth muscle cells close to the threshold for generating APs at the peaks of slow waves

To trigger peristalsis, mechanical stretch and excitatory NTs are necessary for causing depolarization of smooth muscle cells to above threshold for triggering APs (parasympathetic stimulation is excitatory for GI motility, sympathetic is inhibitory)

Question 9

Gastric Accommodation

Answer 9

Gastric accommodation/receptive relaxation is the relaxation of the stomach in response to the entry of food during swallowing (allows stomach to store a large amount of food with minimal increase in transmural pressure), mediated by the enteric and parasympathetic nervous systems

Question 10

Gastric Peristalsis and Factors of Gastric Emptying

Answer 10

Two functions: mixing food for digestion and emptying of gastric content into duodenum via the pyloric sphincter

Gastric emptying is determined by the physical and chemical characteristics of gastric content (physical state, caloric content, tonicity, CCK, and temperature) -

Physical state - gastric emptying of liquid is faster than that of solids (if both are present, liquids are emptied first and solids are delayed until the large solids are broken up into small particles)

Caloric Content - Approximately 4kcal/min for optimal absorption in small intestine - and gastric emptying of fats is slower than carbs or proteins because caloric content of fat is highest between these 3

Tonicity - Emptying of isotonic content is faster than hypertonic and hypotonic contents

CCK - cholecystokinin is released by small intestine in response to luminal fat and protein and it inhibits gastric emptying

Temperature - Decrease in temperature slows gastric emptying, increase speeds it up

Question 11

Defecation and Regulation

Answer 11

Expulsion of rectal content to exterior through anus (important for elimination of undigested products from GI tract) - normal frequency ranges from 3/day to 3/week and is regulated by ANS and somatic nervous system

Parasympathetic nervous system - regulates contraction of colon, rectum, and inhibits contraction of internal anal sphincter (which is also innervated by the sympathetic nervous system, it stimulates the contraction of the sphincter)

Somatic nervous system - regulates contraction of external anal sphincter for voluntary control of defecation

Question 12

Phases of Defecation

Answer 12

Basal Phase - anal canal is closed due to tonic contractions of the internal and external anal sphincters (happens at rest), colonic peristalsis propels GI content from colon into rectum causing accumulation of content in rectum and rectal distension

Pre-Defecation Phase - Rectal dissension activates the mechxnosensitive sensory pathway to the CNS where it triggers the recto-anal inhibitory reflex resulting in urge for defecation, relaxation of internal anal sphincter and contraction of external anal sphincter for maintaining continence

Expulsion Phase - Rectal pressure increases as a result of voluntary straining of abdominal muscles and involuntary colorectal contraction (and simultaneously, anal pressure decreases as a result of voluntary relaxation of external anal sphincter and pelvic floor muscle and involuntary relaxation of the internal anal sphincter bc of recto-anal inhibitory reflex), expulsion occurs when rectal pressure exceeds anal pressure

Termination Phase - Sense of complete rectal evacuation causes the cessation of activities for defecation and return of internal and external sphincters to state of contraction

Question 13

Anal Sphincter Roles

Answer 13

Internal anal sphincter is primarily responsible for resting anal continence

The skeletal muscle cells forming external and internal sphincter are unique in having tone at rest (most skeletal muscle cells are in relaxed state at rest)

Question 14

GI Secretions (overview)

Answer 14

Cells at different segments of the GI tract secrete mucous, digestive enzymes, Hal, bicarbonate, and hormones - all segments secrete mucous for protecting epithelial cells from digestive enzymes and reducing friction for movement of content along tract

Stomach specializes in secreting Hal and pepsinogen for protein digestion and intrinsic factor for intestinal absorption of vitamin B12

Pancreas specializes in secreting bicarbonate and enzymes into the small intestine for the neutralization of acid and digestion of carbohydrates, proteins, and fats

Liver secretes bicarbonate and bile into small intestine for neutralization of acid and emulsification of fat

Question 15

Oral Secretions

Answer 15

Salivary glands (exist beneath the tongue, beneath he jaw and behind the mouth) secrete amylase into the oral cavity for digestion of polysaccharides (example - starch into mono and disaccharides), digestion of polysaccharides begins in the mouth but the extent there is limited because food is in mouth for short period of time before entering esophagus

Question 16

Major Secretory Cells in Gastric Pits

Answer 16

Types of cells: G cells, Chief Cells, Parietal Cells, Mucus Cells

G Cells - endocrine cells that secrete hormone gastrin into circulation for regulation of gastric secretions

Chief Cells - secrete proenzyme pepsinogen into stomach where it is covered by acid (HCl from parietal cells) to the active enzyme pepsin for protein digestion (pepsin also catalyzes the conversion of pepsinogen to pepsin amplifying the effect of acid on pepsin formation)

Parietal Cells - secrete HCl for activation of pepsinogen and intrinsic factor for intestinal absorption of Vitamin B12 (water-soluble, membrane-impermeable molecule necessary for DNA synthesis and cellular energy production) - the intrinsic factor B12 complex formed in stomach goes to small intensity where the complex is endocytose by intestinal epithelial cells for lysosomal degradation and transport into circulation

Mucus Cells - secrete mucus

Question 17

Phases of Gastric Acid Secretions (for increase and decrease)

Answer 17

Cephalic Phase - stimulation of gastric acid secretion by anticipation of food intake (sight/thought/smell/taste of food), mediated by parasympathetic stimulation of parietal cells (post-ganglionic parasympathetic NT ACh activates muscarinic ACh receptors on parietal cells) - loss of appetite of depression signal the cerebral cortex and cause of lack of stimulation to parasympathetic center and inhibit stomach secretory activity

Gastric Phase - stimulation of gastric acid secretion by the presence of food in the stomach, stomach dissension activates stretch receptors and food chemicals and rising pH activate chemoreceptors (phase is regulated by gastric hormones, a local mediator and the enteric nervous system), G cells secrete gastrin into circulation which directly stimulates gastric acid production by activating gastrin receptors on parietal cells and it also indirectly stimulates gastric acid production by stimulating release of histamine from ECL cells to interstitium where histamine stimulates acid production by parietal cells by activating histamine receptors (D cells in the stomach function as a negative feedback mechanism by releasing the inhibitory gastric hormone somatostatin in response to acidity in the stomach, somatostatin inhibits acid secretion by parietal cells by mining to somatostatin receptors) - enteric neurons release ACh that activates muscarininc ACh receptors on parietal cells - if there is excessive acidity in the stomach or emotional distress the sympathetic nervous system will be activated and override parasympathetic control and inhibits stomach secretory activity

Intestinal Phase - Refers to inhibition of gastric acid production in response to presence of nutrients in duodenum (presence of low pH and partially digested food in the duodenum as stomach empties) mediated by enteric nervous system and intestinal hormones (CCK, secretin, etc.) causes gastrin release into the blood and stimulates stomach secretory activity -

Question 18

Mechanism of HCl Secretion by Parietal Cells

Answer 18

Intracellular carbonic anhydrase catalyzes reaction of CO2 with water to form carbonic acid which then dissociates into H+ and HCO3-, H+ is pumped into stomach lame by H+/K+-ATPase on luminal membrane of parietal cell (K+ is also pumped into the cell but diffuses back to stomach lumen via K+ channels on luminal membrane)

HCO3- is transported out of cell into circulation in exchange with Cl- transported from circulation into the cell by HCO3-/CL- exchanger on basolateral membrane of parietal cell

Cl- then diffuses from cell into the stomach lumen via chloride channels, giving net result of HCl production into stomach lumen

During gastric acid production, the transport of HCO3- into circulation causes alkalization of blood leaving the stomach “alkaline tide”

Question 19

Pancreatic Secretions

Answer 19

Most important site of digestive enzymes (amylase, protease, and lipase) for digestion of carbs, proteins, and fats

Pancreas secretes bicarbonate and enzymes into the duodenum (first segment of small intestine) for neutralization of acid and digestion of carbs, fats, and proteins

Question 20

Release of Bile by Gall Bladder

Answer 20

Bile salts function as a detergent for breaking up fat into small micelles (thereby increasing the surface area for digestion by pancreatic lipases)

Bile salts are synthesized in the liver and transported back to the gall bladder for storage

The presence of fat in the duodenum induces intestinal secretion of the hormone CCK into circulation, CCK stimulates the contraction of the gall bladder and relaxation of the sphincter of Oddi for the release of bile into the duodenum for fat digestion

After intestinal absorption of fat, 95% of bile salts are reabsorbed by the ileum (the last segment of the small intestine) and returned to the liver via the portal vein

Question 21

Intestinal Digestion and Absorption (Small Intestine, Villi)

Answer 21

Small intestine is most important GI segment for digestion of carbs, protein, and fat and absorption of the digested products

Small intestine has huge amount of surface area for digestion and absorption due to presence of villi (macroscopic finger-like projections) on the intestinal surface and microvilli (microscopic finger-like projections) on the cell membrane of intestinal epithelial cells

Each villus contains intestinal epithelial cells on the surface of the villus for digestion and absorption and blood and lymphatic capillaries in the middle of villus for the absorption of digested products

Intestinal epithelial cells contain microvilli that face the intestinal lumen (microvilli are also known as brush border), they substantially increase the surface area for absorption of nutrients by intestinal epithelial cells and they also contain membrane-anchored enzymes for the digestion of disaccharides to monosaccharides and small peptides to Amino acids

Globlet cells secrete mucus that lubricates the intestinal tract for peristaltic movement of content along the intestine

Question 22

Carb Digestion and Absorption

Answer 22

Digestion of complex carbs consists of two separate enzymatic reactions: breakdown of polysaccharide to disaccharide and breakdown of disaccharide to monosaccharide

Salivary and pancreatic amylases catalyze the breakdown of polysaccharides (like starch and glycogen) into disaccharides (ex. lactose, maltose, sucrose)

Glucose and galactose are transported into intestinal epithelial cells by SGLT1 sodium-glucose co-transporter (situated on luminal membrane of cell), this secondary active transport is driven by the Na+ gradient and enables complete intestinal absorption of galactose and glucose against their concentration gradients and establishes high concentrations within the intestinal epithelial cells. Glucose and galactose then diffuse down their concentration gradients via the GLUT2 glucose carrier (found on basolateral side of membrane intestinal epithelial cells) to enter circulation

Fructose enters intestinal epithelial cells passively by facilitated diffusion via the GLUT5 glucose carrier on the luminal membrane and then diffuses down its concentration gradient via the GLUT2 glucose carrier (on basolaterial side of membrane intestinal epithelial cells) - also some fructose is converted glucose by isomerase in the inside the intestinal epithelial cell - because of the passive mechanism for intestinal fructose absorption, this limits human tolerance of fructose intake (excessive intake can result in accumulation of residual fructose in the GI tract for bacterial fermentation, flatulence, and abdominal discomfort)

Question 23

Protein Digestion and Absorption

Answer 23

Exogenous proteins from food and endogenous proteins from dead cells and enzymes are digested by enzymes released by exocrine glands in the stomach and pancreas and by enzymes found on the brush border of intestinal epithelial cells

Chief cells in stomach secrete proenzyme pepsinogen which is converted to active pepsin by high acidity in the stomach (which is also the best environment for pepsin to function in) - protein digestion by pepsin and mechanical churning in the stomach covered ingested food into chyme, a mixture of fluid and fine particles of food

Opening of the pyloric sphincter releases chyme into the duodenum where acid in chyme is neutralized by bicarbonate secreted by the pancreas, thereby optimizing the pH for digestion by pancreatic enzymes

Pancreatic proteases and brush-border protease together catalyze the breakdown of proteins into dipeptides, small peptides, and amino acids - dipeptides and small peptides are transported from the lumen into intestinal epithelial cells via peptide transporters (ex. PEPT1) and then broken down by intracellular peptidases into amino acids, amino acids are transported from the lumen into intestinal epithelial cells via Na+/amino acid cotransport and carrier mediated facilitated diffusion and are transported from inside the cell to circulation via carrier-mediated facilitated diffusion (some large peptides and proteins are transported across the intestinal epithelial cells by endocytosis at luminal membrane and exocytosis and basolateral membrane)

Question 24

Fat Digestion and Absorption

Answer 24

Digestion of fat is more complicated than carbs and proteins because it is water-insoluble and requires bile for dispersion into micelles

Bile salts are synthesized in the liver, stored in the gallbladder and released into the duodenum - bile acts as a detergent to disperse fat into small micelles (emulsion droplets) that increase the surface area for digestion

Fat is broken down into free FAs and monoglycerides by pancreatic lipase (small and medium chain FAs AKA 4-12 Carbons can diffuse across luminal and basolateral membranes of intestinal epithelial cells into blood capillaries but long chain free FAs and monoglycerides are transported into intestinal epithelial cells via both simple diffusion and FA transport proteins (FATP) situated on luminal membrane and then resynthesizes into triglycerides inside the epithelial cells and assembled into chylomicrons for exocytosis (cholesterol is similarly transported into intestinal cells by protein transporters on liminal membrane and assembled into chylomicrons for exocytosis), lymph in the lacteal transports chylomicrons away from the intestine

Question 25

Glucose Uses (and High and Low Problems)

Answer 25

Glucose is a product of carb digestion and is essential for brain function (brain cells use it almost exclusively for metabolism)

Low plasma glucose concentration can lead to coma and high plasma glucose is toxic to organ systems (sustained high plasma glucose concentration in poorly controlled type 2 diabetes can lead to kidney failure)

normal range - 73-144 mg/mL

Question 26

Low Blood Sugar and Glucagon

Answer 26

Glucagon and insulin are the two most important regulators of glucose homeostasis

When glucose levels are low, pancreatic alpha cells secrete glucagon which stimulates glycogenolysis (breakdown of glycogen to glucose in the liver) thereby increasing plasma glucose concentration to normal levels - glucagon also stimulates gluconeogenesis (the production of glucose from substrates other than glycogen) in the liver and kidney to increase glucose concentration in the blood (ex. AAs, FAs, glycerol and lactate can be used to synthesize glucose by gluconeogenesis) - only liver and kidney can do it because they contain G-6-phosphatase which is critical for glucose synthesis

During heavy exercise, skeletal muscles break down glycogen to lactate which is then circulated to the liver to produce glucose by gluconeogenesis - this shuttling is known as the Cori cycle

Sympathetic stimulation and other hormones (ex. epinephrine, cortisol, and growth hormone) also stimulate the production of glucose by glycogenolysis and gluconeogenesis

Question 27

High Blood Sugar and Insulin

Answer 27

When blood glucose levels are high (ex. after eating a carb heavy meal) pancreatic beta cells secrete insulin (which stimulates cellular uptake of glucose by liver and other organs for glycogen synthesis), this decreases blood sugar levels to normal levels

Insulin is the only hormone capable of decreasing plasma glucose concentration by stimulating glucose uptake

The entry of glucose into pancreatic beta cells via GLUT2 glucose carriers increases the intracellular ATP to ADP ratio which causes the closing of ATP-dependent K+ channels, membrane depolarization, an increase in intracellular Ca2+ concentration, and Ca2+-dependent exocytosis of insulin

Binding of insulin to the insulin receptor on insulin-sensitive cells stimulates intracellular signaling pathways that lead to the expression of GLUT4 glucose carries on the cell membrane for facilitated diffusion of glucose into cells for storage and metabolism (thereby lowing blood glucose levels)

Question 28

Measurements for Glucose Homeostasis

Answer 28

3 Common measures of glucose homeostasis: fasting plasma glucose concentration, blood level of glycated hemoglobin (Hba1c) and oral glucose tolerance test

Fasting plasma glucose concentration - typically measured after overnight fasting is a measure of hepatic production of glucose (fasting concentration higher than 126mg/100mL suggests diabetes), easy to measure but should do multiple over time to evaluate overall glucose homeostasis

Glycated hemoglobin - glucose-conjugated hemoglobin that is formed by the slow reaction between hemoglobin and glucose in the blood (level of glycated hemoglobin in blood reflects relatively long-term glucose homeostasis because the average life span of RBCs is 120 days), normal levels in non diabetic patients is less than 6% (want to control diabetic patients to be at this level), it is a measure of long-term glucose homeostasis but does not directly address the body’s control of plasma glucose concentration at the time of measurement

Oral glucose tolerance - measures time course of plasma glucose concentration after a meal, a plasma glucose concentration of 200mg/100mL at two hours after glucose intake is an indicator of impaired glucose tolerance (it is a sensitive test of the body’s control of blood sugar levels and an indicator for risk of developing diabetes)

Question 29

Negative Feedback Loops in Pancreas

Answer 29

The loops involve two intestinal hormones (secretin and cholecystokinin AKA CCK) which regulate pancreatic secretions of bicarbonate and enzymes in response to intestinal contents

Loop 1 (for neutralization of acid) - high acidity in the duodenum induces intestinal secretion of the hormone secretin into circulation, secretin stimulates pancreatic secretion of bicarbonate for the neutralization of acid, thereby decreasing the acidity of the duodenum

Loop 2 (for digestion of food) - the presence of fat in the duodenum increases intestinal secretion of the hormone CCK into circulation, CCK stimulates pancreatic secretion of enzymes for the digestion of carbohydrates, proteins, and fat (decreasing fat content in the duodenum), CCK causes gallbladder contraction and relaxes sphincter of Oddi in the small intestine

Question 30

Pathway Through Digestive System

Answer 30

Oral cavity –> pharynx –> esophagus –> stomach –> Small Intestine (Duodenum, also connected to pancreas and gall bladder, –> Jejunum –> Ileum) –> Large Intestine (Cecum –> Ascending colon –> transverse colon –> descending colon –> sigmoid colon –> rectum) –> Anus

Question 31

Epithelial Cell Renewal on Villi

Answer 31

Epithelial cells on intestinal villus are constantly renewed by the migration of new cells that are produced by stem cells at the bottom of intestinal crypts - the cell renewal process involves cell proliferation at the bottom of the crypt, cell differentiation near the top of the crypt, cell migration from the crypt to the villus and cell extrusion at the top of the villus

Question 32

Specific Disaccharidases (and lactose intolerance)

Answer 32

Disaccharidases (situated on the brush borders of intestinal epithelial cells), catalyze the breakdown of disaccharides into monosaccharides

Lactase catalyzes the breakdown of milk sugar, lactose, into glucose and galactose - most adults are lactase-deficient and the consumption of untreated milk by these adults can lead to passage of lactose to the large intestine where bacterial consumption of lactose can lead to flaulence and diarrhea (Lactose –> Galactose + glucose)

Maltase catalyzes the breakdown of maltose into glucose (maltose –> 2 glucose)

Sucrase catalyzes the breakdown of sucrose into fructose and glucose (sucrose –> fructose + glucose)

Question 33

Chylomicrons

Answer 33

Transport vehicle (via exocytosis) for triacylglycerides and cholesterol, they consist of inner core of the triacylglycerides and cholesterol and an outer shell of apoproteins and phospholipids

Intestinal epithelial cells exocytose these into lymphatic capillaries which drain into general circulation, during transit through circulation triacylglycerides are hydrolyzed by lipoprotein lipase (found on surface of endothelial cells), to be turned into FAs for uptake by adipose tissue, liver, and muscle

Lymph transports the chylomicrons away from the intestine

Question 34

Gastric Bypass and Banding

Answer 34

Gastric bypass and banding can be used to treat obesity, more effective than non-surgical therapy - surgery to bypass part of the intestines to reduce the amount of nutrients absorbed (in Roux-en-Y bypass a small part of the stomach is used to create a new stomach pouch and the smaller stomach is connected directly to the middle portion of the small intestine, the jejunum to bypass the rest of the stomach and duodenum)

Band is placed around stomach at bottom of esophagus to limit amount of food you can eat to make you feel more full or less full by making food pass more quickly or slowly through stomach

Question 35

Intestinal Segmentation fo Mixing

Answer 35

In addition to peristalsis for propelling the food through there are segmentation contractions (esp. in small intestine) where segmental rings contract and mix the substance

Question 36

Peptic Ulcer

Answer 36

Helicobacter pylori infects the lower part of the stomach and cases inflammation of the gastric mucosa (usually asymptomatic), gastric inflammation may lead to duodenal or gastric ulcer and complications can include bleeding or perforated ulcer

Question 37

Type 1 Diabetes

Answer 37

Disease characterized by abnormally high blood glucose levels and urinary excretion of glucose because glucose load exceeds reabsorptive capabilities of renal tubules (also known as insulin-dependent diabetes), higher dependence on lipolysis and protein metabolism

Type 1 diabetes - autoimmune disease, pancreatic beta cells are destroyed by the immune system and the absence of insulin means that blood glucose levels are abnormally high and intracellular glucose concentration is low because cells are unable to take up glucose in the absence of GLUT4 carriers in the cell membranes - the abnormally low glucose levels in cells causes an increase in breakdown of triacylglycerides into free FAs which are metabolized by the liver to ketone bodies (B hydroxybutyrate and acetoacetone), and high levels of ketone bodies can lead to ketoacidosis, coma, and death

Patients with Type I diabetes are treated with subcutaneous insulin injections

Question 38

Type 2 Diabetes

Answer 38

Insulin resistance - cause by dysfunction in the insulin receptor-coupled signaling pathways (obesity is a significant risk factor for this disease), most will have high blood sugar levels without ketoacidosis because the level of insulin in plasma is usually sufficient to suppress excess lipolysis, can lead to inflammation, cell proliferation and atherosclerosis

Despite presence of insulin, calls fail to insert sufficient GLUT4 carriers into the cell membrane so plasma glucose levels remain abnormally high - long term overstimulation of pancreatic beta cells by high blood glucose can eventually lead to beta cell failure and loss of insulin secretion (may develop sudden decrease in insulin production and cause ketoacidosis), they eventually become insulin dependent when the beta cells die

Treated with drugs to increase insulin sensitivity of cells or to stimulate insulin secretion by pancreatic beta cells - or inhibitors of the Na+-glucose cotransporter (SGLT2) that inhibit renal reabsorption of glucose to increase urinary excretion of glucose and lower blood glucose levels

Question 39

Metabolism During Absorptive State

Answer 39

1. Digested nutrients enter blood stream from intestine causing blood sugar concentration to increase
2. Release of digested nutrients into blood stimulates insulin release by the pancreas which increases the uptake of glucose by all body cells, reducing the blood glucose concentration back to homeostasis
   3a. In the absorptive state, liver cells convert excess glucose to glycogen for storage via the intermediary G6P and Amino Acids are also converted into ketone bodies that can later by converted to acetyl CoA when needed
   3b. In the absorptive state, muscle cells convert excess glucose to glycogen for storage via G6P, amino acids are used to synthesize actin and myosin to rebuild muscle fibers
   3c. In the absorptive state, adipose cells store excess lipids, increasing fat reserves

Question 40

Metabolism During Post-Absorptive State

Answer 40

1. No nutrients enter the bloodstream from the digestive system
2. Sugar concentration in the blood drop, stimulating the pancreas to stop releasing insulin and start releasing glucagon
   3a. In liver, Glycogenolysis releases glucose into the blood to return blood glucose concentration back to normal, ketone oxidation also releases lipids and additional glucose which body cells can use to generate ATP
   3b. In muscle cells, glucose is released into the blood to increase blood glucose levels and catabolized amino acids from muscle proteins can also generate ATP after undergoing ketogenesis and ketone oxidation in the liver
   3c. Adipose cells release stored lipids which can be used to generate glucose, ketone bodies, or ATP

Question 41

Mechanism of Insulin-Induced Glucose Uptake

Answer 41

Insulin binds to cells, causes them to put glucose transporters into cell membrane, glucose enters cells, some is converted to glycogen for storage others are broken into pyruvate and turned into FAs for storage

Question 42

Mechanism for Exercise-Associated Hypoglycemia and Hyperglycemia in Type I Diabetes

Answer 42

Hypoglycemia: aerobic exercise, insulin fails to increase during moderate aerobic exercise and blood glucose levels decrease causing hypoglycemia

Hyperglycemia: anaerobic exercise, insulin fails to increase sufficiently following anaerobic exercise so blood glucose levels increase

Question 43

Regulation of Fat Metabolism and Mechanism of Fat Breakdown

Answer 43

Lipolysis is the breakdown of triglycerides to nonesterified FAs and glycerol which is an important mechanism for supporting metabolism in organs (because FAs are utilized by most non-neuronal cells including cardiac and muscle cells for energy metabolism), and the liver and kidneys can convert glycerol and FAs to glucose for utilization by neuronal cells

Triglyceride —> diacylglyceride + 1 FA (by hormone-sensitive lipase, HSL and ATGL)

Diacylglyceride —> monoacylglyceride + 1 FA (by HSL)

Monoacylglyceride —> glycerol + 1 FA (by MGL)

HSL is activated by sympathetic stimulation, epinephrine, and glucagon and is inhibited by insulin - the cellular mechanism of HSL activation includes activation of adenylate cyclase, generation of cAMP, activation of cAMP-dependent-kinase and HSL phosphorylation

During moderate exercise, FA oxidation increase 5-10 fold due to availability of FAs produced by activated HSL in fat cells in response to high levels of sympathetic stimulation, epinephrine and glucagon and low levels of insulin

Question 44

Regulation of Appetite by Hormones

Answer 44

Multiple hormones and peptides released by GI cells and adipocytes regulate primary center for appetite control (in hypothalamus)

Most are appetite suppressors (anorexigenic molecules) that provide the satiety sensation after enough food has been eaten - these include CCK, GLP-1, OXM, PYY, insulin, and leptin

Some appetite stimulants (orexigenic molecules) provide the hunger sensation during fasting - these include gastric hormone ghrelin and adipose hormone adiponectin

Eating food leads to gradual increase in anorexigenic molecules and decrease in concentration of orexigenic molecules resulting in satiety and suppression of further food intake (fasting causes the opposite)

By Cells Type
Pancreas - Insulin decreases appetite
Intestinal Cells - CCK, GLP-1, OXM, PYY decreases appetite
Adipose Tissue - Leptin decreases appetite
Stomach - Ghrelin increases appetite

Question 45

Glucose-sensing system

Answer 45

A glucose-sensing system exists in the hepatic portal vein and detects the glucose concentration in hepatic portal venous blood which can send signals to the vagus nerve via the hypothalamus to suppress food intake - glucose excited and glucose inhibited neurons in hypothalamus also regulate appetite

Question 46

Cerebral Override of Appetite

Answer 46

To a certain extent, the cerebral cortex can override peripheral signals to the hypothalamus for the regulation of appetite - for example in anorexia nervosa there is excessive weight loss as a result of extreme dieting and physical activity

Excessive eating can also contribute to the development of obesity (affected by external factors like availability of favorite food in large portions at low costs) can override satiety signals and lead to excessive eating