Lecture 21 Flashcards
the pancreas is a _____ structure about _______cm in length
Located in the _____________
Has both _____________ function
Consists of a _____________
99% of its cells are arranged in clusters called ______
Flat
12.5-15
C-shaped curvature of the duodenum
exocrine and endocrine
head, neck, body and tail
acini
Acini produce digestive enzymes that flow into the digestive tract through pancreatic ducts
Scattered among acini are 1-2 million tiny clusters of endocrine tissue called ____________
Abundant capillaries serve both the exocrine and endocrine tissue
pancreatic islets or islets of Langerhans
many different cells in islets of the langerhans
alpha cells or A cells are about ____% and release _____
17%
glucagon
Beta cells or B cells consist of ___% of the population and are responsible for _____ and _____
regulates glucose release by _____________
70%
insulin and amylin
amylin is co-secreted with insulin
regulates glucose release by delaying gastric emptying
Delta or D cells are ______% population
responsible for ___________ (identical to a growth hormone inhibiting hormone secreted by hypothalamus)
inhibits ____________
7%
somatostatin
insulin and glucagon
E cells are ____% of the population and responsible for ______
Stimulates __________
Stimulates ________
Inhibits _____________
5%
ghrelin
growth hormone release
appetite
insulin secretion
F (________-) cells
____%
Inhibits __________
stimulates ______________
Pancreatic P polypeptide
1%
intestinal motility
gastric and intestinal enzyme secretion
what does glucagon do?
INCREASE BLOOD GLUCOSE LEVEL
what does insulin do?
lower blood glucose level
insulin is a Small protein composed of____ chains held together by ______ bonds
Produced by ______cells of the pancreatic islets
two
disulfide
beta cells
insulin process
Step 1
- Synthesized as ________ in the _______ of the ______
Step 2
- cleaved into ______
Step 3
- is then transported to the ______ and packaged into ________
then cleaved into __________
Secretory granules of insulin then accumulate in the ______
preproinsulin
ribosomes
endoplasmic reticulum
proinsulin
golgi
secretory granules
insulin and C peptide
cytoplasm
insulin makes glucose move into all cells at a more _____ rate (especially muscle and adipose tissue).
Insulin also causes all cells to use ______ for cellular processes (metabolism, growth, short-term energy, storage)
rapid
glucose
_________ are present in all tissues throughout the body, and have a VERY high affinity for glucose (easily makes it’s way into body tissues).
Insulin upregulates their uptake to replace glucose that has been used up in these cells (indirect effect).
Glut1 & Glut3
_____ is present on the liver and the Pancreas, has a_____affinity for glucose movement into the cell.
Pancreatic Glut receptors are the________receptors (very important!!)
Liver Glut receptors remove excess glucose from the blood, convert to______ (with insulin = inactivation of liver _______, increased _______)
Glut2
lower
insulin feedback
glycogen
phosphorylase
glucokinase
______ is present in Muscle and adipose cells, has a relatively high affinity (though not as high as Glut1 & 3
Glut4
Glut4: One of 14 members of the GLUT family of ______ transporters
- High-affinity glucose transporter
- expressed in muscle cells and adipocytes
- Insulin stimulates the accumulation of GLUT4‑containing vesicles at the periphery of the cell within ______ of exposure to the hormone
- But, without insulin, only ~____% of the total transporter pool is found on the cell surface
Early step in the development of _______ results from failure of GLUT4 to translocate to the plasma membrane (_______)
facilitative transmembrane hexose
5 minutes
5%
insulin resistance
(type 2 diabetes mellitus)
Insulin Regulation
Glucose key regulator of insulin secretion, occurs ____ min
Glucose levels > _____ mg/dL stimulates insulin synthesis (typically after meals)
Glucose is transported into the _____ cell by glucose transporters (_____)
_______ phosphorylates the glucose resulting in ________ - producing ATP
ATP closes _____ channels
3-5
108
beta cell
GLUT2
Glucokinase
glucose-6-phosphate
K+
role of cytosolic ATP
- ATP binds to the ____ ATP channels, causing channel closure
- ___ can no longer leave the ____
- Membrane potential of the beta-cell shifts to a more ____ value, (____mV to____mV and above) causing membrane _______
- Opens voltage gated _____ channels increasing ______
- Increases in intracellular calcium is the primary trigger for ______ of insulin-containing secretory granules
K
K+
beta-cell
positive
-60
-20
depolarization
Ca++
cytosolic Ca++
exocytosis
Repolarization after this process involves movement of ____ out via channels activated by depolarization
Also pushed toward repolarization by inactivation of ___ channels
(____mV) is resting state for membrane potential in the Beta cells
K
Na
-60
(K ATP) channels house ________ receptors
________ bind to these receptors on beta-cells
Binding closes the linked ATP-sensitive ________ channels
Leads to decreased _______ efflux and depolarization of the cell membrane
Voltage-dependent ______ channels open
Influx of _____, causing translocation and exocytosis of secretory granules of _____ to the cell surface
sulfonylurea (SUR-1)
Sulfonylureas
potassium
potassium
calcium
calcium
insulin
Inactive by-product of the cleavage of proinsulin to active insulin is _______
c peptide
C peptide is cleared ______than insulin (marker of insulin secretion)
Its presence indicates __________ of insulin
The half-life of C-peptide in the blood is about _____.
C-peptide is largely excreted by the ______
A random C-peptide level has reasonable discriminatory power for determining type 1 vs type 2 diabetes
more slowly
endogenous release
30 min
kidney
Insulin is secreted into the __________,
~____% is degraded by the liver
Remaining insulin enters the systemic circulation where it binds to receptors in target sites (skeletal muscle)
Insulin receptor binding stimulates enzyme (_______) activity
portal venous system
50%
tyrosine kinase
Activated receptors recruit intracellular signaling molecules (________________)
Activation of variety of insulin receptor signaling pathways induces:
Glycogen _______
Protein ________
__________
Regulation of various genes in insulin-responsive cells
insulin receptor substrates
synthesis
synthesis
Lipogenesis
Hormone preventing synthesis of glucose from non-carbohydrate carbon sources in the liver (_____________)
Promotes glucose uptake into muscle and adipose tissue
Accelerates facilitated diffusion of glucose into cells
____% of insulin-stimulated glucose uptake-skeletal muscle
____% of insulin-stimulated glucose uptake-adipose tissue
gluconeogenesis
90%
10%
Insulin Acts to:
Speed conversion of glucose to glycogen by activating the enzyme ___________
Increase uptake of ____________ into cells
Increase ______ synthesis
Speed synthesis of _________
Slow the conversion of glycogen to glucose (_________) by inhibiting the enzyme ___________
Slow the formation of glucose from amino acids and lactic acid (gluconeogenesis)
glycogen synthase (glycogenesis)
amino acids
protein
fatty acids
glycogenolysis
glycogen phosphorylase
Increase rate of glucose transport into almost all cells AND stimulate glucose usage by almost all cells
If not for this function, all cells would be getting way too much glucose and suffer the consequences
this is direct or indirect?
both
Adipocytes and striated muscle cells have extra GLUT receptors (GLUT-4) and NEED INSULIN to _________
direct or indirect ?
get those receptors to the surface
direct
Since insulin reception on almost all cells (except brain neurons) increases glucose usage, then those cells will also uptake glucose via their established membrane receptors to ____________
this is direct or indirect?
replace what they used
indirect
During much of the day, muscle depends on ______ for energy from Internal storage supply
Basal glucose uptake is relatively _____ in muscle
GLUT-1 and GLUT-3 don’t supply enough glucose to fuel metabolism
Insulin level in the blood between meals is too low to have enough GLUT-4 receptors on the membrane to fuel metabolism
When available, muscle PREFERS ________ as energy source
fatty acids
low
glucose
Muscle Exceptions:
Mealtime/few hours after (glucose absorption by intestines and beta cell release of insulin and GLUT-4 receptors are on membrane)
(____ Glucose uptake)
During moderate-to-heavy exercise (_______ GLUT-4 receptors on membrane)
↑
increases
If muscles are not exercised after a meal, then the entering glucose is stored as glycogen (↑ Glycogen synthesis)
Insulin reception activates ________
Can be used later as fuel (Proper storage of glucose = GOOD!)
glycogen synthase
Most of the glucose absorbed after a meal is RAPIDLY stored in the ______ in the form of glycogen
Between meals, glycogen is split back into glucose and released back into the blood to keep the glucose concentration from falling too low
liver
Insulin effects on liver:
Inactivation of liver _________
Principal enzyme of _________ (splitting liver glycogen into glucose)
Increased activity of ________
- Enzyme that phosphorylates glucose after its inward diffusion
- Enhances inward diffusion of glucose from blood (to replace it)
(_____ Glycogen synthesis)
NET EFFECT: INCREASE LIVER GLYCOGEN
PROPER GLUCOSE STORAGE = GOOD!
phosphorylase
glycogenolysis
glucokinase
↑
Insulin effects:
When the quantity of glucose entering liver is MORE THAN CAN BE STORED AS GLYCOGEN or can be used for LOCAL HEPATOCYTE METABOLISM, insulin promotes conversion of excess glucose into __________ which are subsequently packaged as ____________ in ________. They are TRANSPORTED via blood to ___________
GOOD! = Proper storage of excess glucose!
_______ Lipogenesis
______ quantities and activities of enzymes of gluconeogenesis (____ Gluconeogenesis)
FATTY ACIDS
TRIGLYCERIDES in Very Low Density Lipoproteins
ADIPOSE TISSUE
↑
Decreases
↓
insulin’s effects on adipose tissue
- Activates ____________ in the capillary walls of adipose tissue
- Splits the arriving triglycerides back into ______
- Fatty acids can be absorbed into the ________
- In adipocytes, converted BACK to _________ and stored
- Inhibits ___________ (____ Lipolysis)
- Inhibits the ________ of stored triglycerides, preventing fatty acid release back into the blood
lipoprotein lipase
free fatty acids
adipocytes
triglycerides
hormone-sensitive lipase
↓
hydrolysis
insulin _______ glucose transport through cell membrane into fat cells (translocation of GLUT-4) (____ Glucose uptake)
Glucose is PRIMARILY USED to make _______ which supplies ______ that combines ______ to form TRIGLYCERIDES (____ Lipogenesis)
Some of the entering glucose is used to synthesize small amounts of fatty acids
GOOD! = Proper storage of
excess glucose!
Promotes
↑
alpha-glycerophosphate
glycerol
fatty acids
↑
_________ are released from the GI tract following food ingestion and increase insulin secretion and suppress glucagon secretion
Incretins
_________ is the most potent incretin
stimulates insulin secretion when the blood glucose is above the fasting level
Glucagon-like peptide 1 (GLP-1)
- _________ stimulates alpha cells to release glucagon
- Acts on the _______ which accelerates conversion of ______ into ______ (_______). Promotes formation of glucose from ______ and ___________ (__________)
Hepatocyte release of glucose into the blood - Hyperglycemia:
_______ alpha cell secretion of glucagon (______ feedback)
Low blood glucose
hepatocytes
glycogen into glucose (glycogenolysis)
lactic acid and amino acids (gluconeogenesis)
inhibits
negative
stimulatory regulators of GLUCAGON or inhibitory ?
- acetylcholine innervation of islets
- fatty acids
- insulin
- hyperglycemia
- norepinephrine/epi
- amino acids
- somatostatin
- stimulatory
- inhibitory
- inhibitory
- inhibitory
- stimulatory
- stimulatory
- inhibitory
stimulatory regulators of INSULIN or inhibitory ?
- acetylcholine innervation of islets
- fatty acids
- grelin
- amino acids
- norepinephrine/epi
- gastrin, secretin
- somatostatin
- gastric inhibitory peptide
- sulfonylureas
- stimulatory
- stimulatory
- inhibitory
- stimulatory
- inhibitory
- stimulatory
- inhibitory
- stimulatory
- stimulatory
