pancreas Flashcards
the exocrine pancreatic secretions ( ____ ____ and various digestive enzymes, together called ____ ____ ) are secreted into ducts that converge to from the ____ ____ , which joins the ____ ____ ____ from the liver to form the ____ ____ ____ , which enters the duodenum
bicarbonate ions
pancreatic juice
(main) pancreatic duct
common bile duct
amuplla of vater
ezymes are secreted by cells at the “pancreatic” end of the duct system; bicarbonate ions are secreted by epithelial cells lining
the walls of the ducts themselves
HCO3- is tranposrted out of the cells of pancreatic ducts and into the duct lumen by a countertransport protein that also carries
Cl-
enterokinase, an enzyme embedded in SI mucosal (duodenual) epithelial cells, splits off a piece of the zymogen ____ , forming the active enzyme ____
trypsinogen
trypsin
when trypsin is activated, it
splits peptide fragments off of other pancreatic zymogens, activating those enzymes
trypsin inhibitor, a substance formed in the cytoplasms of the pancreatic glandular cells
prevents activation of trypsin inside the pancreatic secretory cells and in the pancreatic ducts
the secretions rates and characteristics of pancreatic juice are partly determined by the types of food in the chyme within the duodenum:
increased acidity in duodenum → ____ → ____ → ____ → ____ → neutralization of acid in SI
increased secretion of secretin from SI → increased plasma secretin → Pancreas: increased bicarbonate secretion → increased flow of bicarbonate into SI
the secretions rates and characteristics of pancreatic juice are partly determined by the types of food in the chyme within the duodenum:
increased amino and fatty acids in duodenum → ____ → ____ → ____ → ____ → increased digestion of proteins and fats in SI
increased secretion of CCK from SI → increased plasma CCK → pancreas: increased enzyme secretion → increased flow of enzymes into SI
pancreatic exocrine secretion is also increased by the release of ____ from parasympathetic (mostly vagal) neurons to the pancrease in rsponse to the taste of food and stomach distention
(this is not as important as secretin and CKK secretion)
acetylocholine
endocrine pancreas:
hormones are secreted by cell clusters called ____ ____ ____ , which alpha cells secreting ____ and beta cells secreting ____
islets of langerhans
glucagon
insulin
metabolism
the chemical rxns that occur in a living organism (includes anabolism, or the rxns that build organic molecules, and catabolism, or rxns that break down organic molecules)
absorptive state (right after meal):
ingested nutrients are entering the blood from the GI tract; some ingested nutrients provide the body’s energy requirements and the rest are added to teh body’s energy stores
post-absorptive state:
the GI tract is empty of nutrients, and energy comes from the body’s own stores (for many folks, late morning, late afternoon, late evening, and most of the night)
absorptive state: absorbed carbs
- the main energy source is glucose (____ and ____ are either converted to glucose by the liver or enter the same metabolic pathways as glucose; thus we will consider all absorbed carbs to be glucose)
- much of the glucose enters cells and is catabolized to ____ and ____ ____ , thereby producing ____
- skeletbal muscle not only burns (oxidizes) glucose to make ATP, but also converts some glucose into:
- adipocytes also burn a little glucose, but mostly transform it into ____
- oversimplified, an adipocyte uses glucose to form fatty acids and ____ phosphate, and then puts these two together to make triglycerides. (adipocytes cannot make triglycerides from glycogen)
- galactose and fructose
- water and carbon dioxide ATP
- the polysaccharide glycogen, an energy storage molcecule
- triglycerides (fats)
- alpha-glycerol
absorptive state: absorbed carbs:
- there is net uptake of ____ by the ____, which stores it as glycogen or uses it to make triglycerides (by first using it to form fatty acids and alpha-glycerol phosphate). some of the resulting fat is stored in the liver and some is packaged with specific proteins to make ____ , which are then moved into the blood and which do not easily cross capillary walls
- most of the fatty acids in the triglycerides within VLDLs end up being stored as triglycerides in ____ tissue: as the triglycerides are hydrolyzed to monoglycerides and fatty acids by enzymes found on the blood-facing surfaces of capillary endothelial cells as blood flows through adipose tissue, the fatty acids thus generated diffuse from the capillaries into the adipocytes where they are used to form triglycerides once agin
- glucose liver VLDLs
- adipose
absorptive state: absorbed lipids:
many of the absorbed lipids are within ____ in plasma
the triglycerides in chylomicrons are hydrolyzed to ____ and ____ ____ by enzymes and the fatty acids thus generated diffuse from capillaries into adipocytes where they are used to form triglycerides once again
chylomicrons
monoglyercides fatty acids
absorptive state: absorbed lipids:
small amounts of ingested fat, rather than being stored, are oxidized by various organs to provide ____. (the relative amounts of carbs and fat used for energy during the absorptive state mostly depends on the content of the meal)
energy
absorptive state: absorbed lipids:
one lipied in chylomicrons, _____ , does not serve as an energy source, but rather is used as a component of ____ ____ and a precursor for ____ hormones, bile salts, etc
cholesterol
plasma membranes steroid
cholesterol gain by the body:
- *
- some dietary cholestoerl is absorbed, eventually entering the plasma in lipoproteins, and some is excreted in feces
- although most cells can make cholesterol, they can’t make enough to suit their needs and thus most cells remove cholesterol from the blood
- liver cells and cells lining the GI tract, can make large amounts of cholesterol, most of which enters the blood
cholesterol loss from the body:
- *
- some plasma cholesterol is taken up by liver cells and placed into the bile, which carries it to the SI lumen for elimination in feces (although some is reabsorbed by the SI)
- some plasma cholesterol that is taken up by liver cells is used to make bile salts (many of these are reabsorbed in the intestines)
all of the hepatic cholesterol processes undergo some degree of regulation in an attempt to keep plasma cholesterol within the normal range, with the most important one being:
when dietary and plasma cholesterol levels rise, the enzyme ____ ____ , necessary for cholesterol synthesis by the liver, is inhibited
the rate at which the liver synthesizes cholesterol
HMG-CoA reductase
absorptibe state: absorbed proteins:
some amino acids are absorbed into the liver and used to build proteins or converted to ____ ____ called ____ ____ by deamination (removal of the amino group)
the amino group is used to make ____ in the liver, which enters the blood to be excreted by the kidney
carbohydrate-like intermediates alpha-keto acids
urea
absorptive state: absorbed proteins:
alpha-keto acids can enter the ____ ____ and be used to produce ATP for ____ cells or be converted by liver cells to ____ ____
even more amino acids enter the non-liver cells are used to make ____
kreb’s cycle liver fatty acids
proteins
absorptive state: absorbed proteins:
there is a net ____ of proteins during the absorptive state, but they just replace proteins broken down during the postabsorptive state
any amino acids in excess of those needed to maintain a stable rate of protein turnover are converted to ____ or ____
synthesis
carbohydrate or fat
postabsorptive state:
brain cells normally can use only ____ for energy; thus the plasma glucose concentration msut be maintained even though no glucose is being added:
glucose
to the blood from the GI tract
glycogenolysis in liver:
signals that trigger this include:
glycogen is converted to glucose 6-phosphate which is converted to glucose, which enters the blood
sympathetic input to the liver
glycogenolysis in skeletal muscle:
some of the lacate produced:
glycogen is converted to glucose 6-phosphate, which enters the glycolysis pathway to yield ATP, pyruvate, and lacate
enters the blood and is taken to the liver, where it is converted into glucose and put into the blood (Cori cycle)
in adipose tissue, triglycerides are broken into glycerol and fatty acids ( ____ ) , which enters the blood
the glycerol reaching the liver is:
lipolysis
converted to glucose (gluconeogenesis), which can be released into the blood
a few hours after glycogenolysis and lipolysis (followed by gluconeogenesis), in muscle and other tissues, proteins are broken into:
amino acids, which enter the blood and are carried to the liver, where some are converted by the alpha-keto acid pathway to glucose (gluconeogenesis) , which is released into the blood
gluconeogenesis can supply only ____ of the enrgy needed by the body
25-50%
glucose sparing
during the transition from the absorptive to the postabsorptive state, most tissues other than those of the nervous system reduce their use of glucose and begin using fat as their major source of energy
this adjustment “spares” the glucose produced by the liver for use by the nervous system
in glucose sparing, the fatty acids released into the blood by lipolysis are taken up and
catabolized by nearly all tissues except nervous tissue and provide energy
fatty acids provide energy by
- *
- undergoing “beta” oxidation to produce acetyl CoA plus hydrogen atoms (which go on to oxidative phosphorylation, yielding ATP)
- the acetyl CoA enters the Kreb’s cycle and is catabolized to water and carbon dioxide, yielding ATP
in liver cells only, most of the acetyl CoA fromed from fatty acids (by beta-oxidation) does not entery the Kreb’s cycle but is
processed into compounds called ketones, which are then released into the blood and serve as an energy source during prolonged fasting; this includes serving as an energy source for tissues of the nervous system
during fasting, fatty acids and ketone use provides energy for the the body while sparing glucose for the ____
the brain can use ketones for energy and it does so increasingly as:
brain
ketones build up in the blood during a fast
when the brain reduces its glucose requirement by using ketones, less ____ breakdown is required to supply amino acids for gluconeogenesis
thus protein stores last longer and the odds of tissues damage during prolonged fasts are ____
protein
reduced
insulin secretion rises during the ____ state and falls during the ____ state
absorptive
postabsorptive
when plasma insulin level is high, it acts on:
- muscle, where it:
- adipose tissue, where it:
- liver, where it:
- increases glucose uptake and use, causes net glycogen synthesis, causes net protein synthesis, and causes net amino acid uptake
- increases glucose uptake and use and causes net triglyeride synthesis
- increases glucose uptake, causes net glycogen synthesis, and causes net triglyceride synthesis
when plasma insulin level is low, the results are:
- in muscle:
- in adipose tissue:
- in liver:
- decreased glucose uptake and use, net glycogen breakdown, net protein breakdown, net amino acid release, and increased fatty acid uptake and use
- decreased glucose uptake and use and net triglyceride breakdown with the release of glycerol and fatty acids
- increased glucose release due to net lgycogen breakdown and gluconeogenesis, and increased ketone synthesis and release
an increase in plasma insulin is the primary cause of the ____ state events
low plasma insulin is the primary cause of the ____ state events
absorptive
postabsorptive
when insulin binds to its membrnae-bound receptor, the intracellular enzyme ____ ____ is activated
tyrosine kinase
when tyrosine kinase is activated, this causes
the phosphorylation (and thus activation) of multiple intracellular enzymes invovled in fat, protein, and glycogen synthesis (and sometimes growth)
the insertion into the target cell’s plasma membrane of glucose transport proteins such as GLUT-4; this results in a greater rate of glucose movement into the cell via facilitated diffusion
when tyrosine kinase is activated, the phosphorylation of some enzymes are inhibit by insulin, this allows insulin for example to
inhibit the breakdown of glycogen to glucose or triglycerides to fatty acids and glycerol
(e.g. glycogen phosphorylase)
80% of the body’s cells markedly increase their uptake of glucose from the blood in response to insulin, but insulin’s actions are especially potent and important in ____ , ____ , and ____ cells
muscle, liver, and adipose cells
in a given target cell, insulin typically utilizes multiple actions/pathways to elicit the target cell’s ultimate ____ to insulin
response
a target cell’s ultimate responses to insulin include
glucose transport (insertion og GLUT transporters)
protein synthesis
fat synthesis
glycogen synthesis
growth and gene expression
brain cells use a different subtype of GLUT, one that
has a very high affinity for glucose and whose presence and/or activity is not insulin-dependent
(brain cells can obtain glucose from the blood even when insulin is low
the main controlling factor for insulin secretion is the plasma ____ concentration, as detected by the ____ cells of the islets of langerhans (high plasma glucose = high insulin secretion rate
glucose
beta
increased plasma glucose → (1) ____ → (2) ____ → (3) ____ (4) ____ → (5) ____ → restoration of plasma glucose to normal
- pancreatic islet of beta cells: increased insulin secretion
- increased plasma insulin
- adipocytes and muscle: increased glucose uptake
- liver: cessation of glucose output; net glucose uptake
- restoration of plasma glucose to normal
other inputs to beta cells to increase insulin secretion
increased plasma amino acids
increased parasympathetic input
a group of gut hormones including glucose-dependent insulinotropic peptide (GIP) and glucagonlike peptide-1 (GLP-1)
other inputs to beta cells in decrease insulin secretion
increased plasma epinephrine
increased sympathetic input
glucagon’s major effects are on ____ cells and oppose those of ____
liver
insulin
in the liver, glucagon increases
glycogen breakdown (glycogenolysis)
gluconeogenesis
ketone synthesis
glucagon increases plasma ____ and plasma ____ , both of which are important to prevent:
glucose
ketones
hypoglycemia during the postabsorptive period
the chief stimulus for glucagon release is a decrease in plasma ____
glucose
epinephrine from the ____ ____ (and increased activity in sympathetic Nn to liver and adipose tissue) increases:
adrenal meduallae
plasma glucose, plasma fatty acids, plasma glycerol, and glucagon secretion
cortisol from the ____ ____ , is secreted in response to _____
adrenal cortex
hypoglycemia
cortisol secreted in response to hypoglycemia increases:
these effects “spare” glucose for the _____ during hypoglycemia, and during fasting, help resist the development of significant hypoglcemia
the plasma levels of glucose, amino acids, and fatty acids and triggers most cells to switch from using mostly glucose to mostly fats as an energy source
brain
the effects of increasing the plasma levels of glucose, amino acids, and fatty acids result mainly from cortisol’s effect of
stimulating gluconeogenesis in the liver
cortisol enhances ____ in adipose tissue, and inhibits glucose uptake from blood by most cells, especially ____ and ____
lipolysis
muscle and adipose
cortisol secretion rises during ____ , and fasting is an important stressor; glucose sparing and the resistance to hypoglycemia aids survival during fasting
stress
growth hormones from the anterior pituitary:
- increases the plasma levels of ____ and triggers most cells to switch from using mostly glucose to mostly ____ as an energy source
- these effects results from GH’s:
- increasing ____ in the liver
- making adipocytes more responsive to ____ stimuli
- decreasing ____ ability to stimulate glucose uptake throughout the body, but especially by ____ and ____ tissue
- glucose fats
- gluconeogensis
- lipolytic
- insulin’s muscle and adipose tissue
the liver serves as an important ____ ____ ____ system
blood glucose buffer
insulin is the most important factor causing
the metabolic switching from the absorptive to the postabsorptive state
insulin keeps blood glucose levels from becoming so high that they
cause tissue damage
5 signals to effectors have effects that are counter to those of insulin:
- ____ , ____ ____ and ____ ____ to the liver and adipose tissue play a major role in preventing hypoglycemia
- ____ and ____ secretion rates are not usually coupled to the absorptive-postabsorptive pattern; nontheless, their blood presence in basal levels is necessary for normal adjustment of lipid and carbohydrate metabolism to the postabsorptive period
- glucagon, plasma epinephrine, and sympathetic neurons
- cortisol and GH
normal fasting blood glucose level
90 mg glucose/100ml of blood (90 ml/dl)
in diabetes, blood glucose commonly rises to
300-1200 mg/100 ml in blood
problems caused by high blood glucose:
- loss of glucose in the urine (amount filtered exceeds ability to reabsorb it)
- cellular dehydration (the excess glucose stays in the ECF, increasing its osmolarity and “drawing” water from the cells)
- extracellular dehydration (increased glucose in the renal filtrate “holds” water in the tubule, decreasing the amount of water reabsorbed into the renal interstitial fluid and then blood)
- tissue injury
high blood glucose levels can can cause tissue injury because blood vessels in multiple locations undergo structural changes; thus blood supply to tissues becomes inadequate, leading to
risk for heart attack, stroke, kidney disease, retinopahty/blindness, and ischemia/gangrene of the limbs; damage to peripheral Nn (including autonomic) results in impaired CV reflexes, impaired bladder control, and decreased sensation in the exremities
in both type I and type II idabetes, uptake and use of glucose by all cells except brain cells is impaired. as a result, blood glucose levels rise, cellular use of glucose ____ , and use of ____ and ____ increases
falls
fats and proteins
type I diabetes (insulin dependent; juvenile)
deficiency of pancreatic insulin (lack of insulin secretion by pancreas)
type I diabetes is caused by:
heredity plays a role in determining the ____ of the beta cells to injury (in some people, beta cells may degenerate even without autoimmune or viral attack
injury to the pancreas’ beta cells, such as by autoimmune disorders or viral infection
susceptibility
average age of onset of type I diabetes is
14, but can occur at any age
in type I diabetes, blood glucose rises, there is increased use of fats for energy, and increased formation of ____ by the liver, and depletion of the body’s ____
cholesterol
proteins
in type I diabetes, the shift from carbohydrate to fat metabolism increases the release of ____ ____ into the blood more rapidly than they can be taken up and oxidized by tissue cells, resulting in ____ ____
keto acids
metabolic acidosis
the metabolic acidosis caused by type I diabetes can lead to
diabetic coma and death unless the patient is treated with large amounts of insulin
in type I diabetes, the excess fat use in the liver over a long time causes large amounts of cholesterol in the blood and increased deposition of cholesterol in arterial walls, leading to
arteriosclerosis and other vascular lesions
in type I diabetes, the increased use of and decreased storage of fat and proteins leads to
weight loos and asthenia (lack of energy) despite polyphagia (eating large amounts of food) which can lead to wasting of tissues (especially due to depletion of the body’s proteins) and death
type II diabetes (non-insulin-dependent; adult onset)
resistance to insulin’s effects
type II diabetes:
initially caused by
decreased cellular sensitivity of target tissues to the metabolic effects of insulin (and transport), called insulin resistance
type II diabetes:
the insulin resistance especially impairs
carbohydrate use and storage
type II diabetes:
onset usually occurs after age 30, often between ____ and ____; the disease typically develops gradually
50 and 60
____ is the mot important risk factor in both children and adults for type II diabetes
obesity
type II diabetes
often associated with increased plasma ____ levels, which occurs as a compensatory response of the beta cells to the insulin resistance/high blood glucose
insulin (hyperinsulinemia)
type II diabetes
most of the insulin resistance may be caused by abnormalities in the signaling pathways that link the insulin ____ with its multiple ____ effects (and impaired signaling may be closely related to the effects of lipid accumulation in tissues)
receptor intracellular
features of metabolic syndrome
- obesity, especially abdominal fat
- inulin resistance
- fasting hyperglycemia
- lipid abnormalities, such as increased blood triglycerides and decreased blood high density lipoprotein cholesterol (good cholesterol)
- hypertension
a major adverse consequence of the metabolic syndrome is increased risk for CV disease, including
atherosclerosis and injury to various organs in the body
insulin resistance (and thus metabolic syndrome) predisposes one to developing type ____ diabetes, which itself is a major cause of CV disease
II
tests used in diagnosis of type II diabetes
urinary glucose
fasting blood glucose
fasting blood insulin
glucose tolerance test
A1c test
glucose tolerance test
when a normal fasting person eats one gram of glucose/kg body weight, the blood glucose level rises from about 90 to 120-140 and falls back to BELOW the starting value in around 2 hours
in a fasting diabetic ingesting this amount of glucose, the blood glucose level nearly always starts at above 110, rises to a much greater extend than in a normal person, and falls back to, BUT NOT BELOW the starting value only fater 4-6 hours
A1c test
a blood test that provides information about the average levels of blood glucose over the past 3 months
oversimlpified: glucose attaches to hemoglobin in RBCs and the test measures the degree of this attachments; the highter the blood glucose level, the more glucose will attach to hemoglobin
with prolonged and severe insulin resistance, the increased insulin levels cannot maintain normal blood glucose.
in early stage of type II diabetes, moderate hyperglycemia occurs after eating ____
in the later stages, the beta cells become exahusted (damaged) and unable to produce enough insulin to prevent more severe ____, especially after eating carbohydrates
carbohydrates
hyperglycemia
some acquired or genetic conditions/factors that can impair insulin signaling and cause insulin resistance and type II diabetes are
polycystic ovary syndrome
excess formation of glucocorticoids (cushing’s syndrome)
excess formation of growth hormone (acromegaly)
insulin shock coma is caused by:
diabetic coma is caused by:
too much insulin
too little insulin
when treating diabetes, in addition to managing insulin and glucose levels, one must also pay close attention to blood ____ levels
lipid
