[os 202c] 20120102 pancreatic islet physiology (insulin)
TRANSCRIPT
-
8/13/2019 [OS 202C] 20120102 Pancreatic Islet Physiology (Insulin)
1/10
11ooff1100JJAAYYVV,,NNIIKKOO,,PPAAMM PPAANNCCRREEAATTIICCIISSLLEETTSSPPHHYYSSIIOOLLOOGGYY
I.THE PANCREASTWO TYPES OF PANCREATIC TISSUES
Exocrine Tissueo Found in pancreatic acinio Secretes pancreatic enzymes & bicarbonates for
digestion
Endocrine Tissueo Found in the Islets of Langerhans, scattered among
the pancreatic acini
o Releases pancreatic hormonesTable 1. Four Major Types of Cells found in the Islets
Beta () cells (most numerous)
- 60%of the total cell type
- Located in the centerof the islets
- Secreteinsulin-1 in 10 becomes diabetic every year
Delta () cells
- 10%of the total cell type
- located peripheral to alpha
cells- Secrete somatostatin
Alpha () cells
- 25%of the total cell type
- Located in the peripheryof the
Islets
- Secrete glucagon
PP cells
-located peripheral to alpha
cells
-Secrete pancreatic
polypeptide
Figure 1.Four Major Cell Types Found in the islet
The arterial system supplies the center of the islet firstbefore supplying the periphery
Berne: If islets are disaggregated experimentally and theindividual cells dispersed, these cells spontaneously reaggregateinto islets if the cells are brought back together again in culture.
Berne: Gap junctions exist between neighboring islet cells andpermit the flow of molecules (that exert possible paracrine
effects) and electrical currents between them.
Insulin produced in the cells influences the secretion ofthe other islet cells in the periphery paracrine effects of
insulin on the outer islet cell types
INSULIN
Is the primary anabolic hormone responsible for maintaining theupper limit of blood glucose levels, done by:
o Promoting glucose uptake and utilization by muscle andadipose tissue
oIncreasing glycogen storage in the liver and muscleoReducing hepatic glucose output
Promotes protein synthesis from amino acids and inhibits proteindegradation in peripheral tissues
Promotes triglyceride synthesis in the liver and adipose tissue andrepresses lipolysis of adipose triglyceride stores
Regulates metabolic homeostasis through effect on satiety(Source: Berne & Levy)
AA..IINNSSUULLIINNSSTTRRUUCCTTUURREE
Figure 2. Structure of Human Proinsulin
Human proinsulin is composed of three parts:o chain - 21 amino acids containing an intrachain
disulfide ring
o chain 30 amino acids; the and the subunits areconnected by two disulfide bridges
oC chainknown as the connecting peptide or C peptide;it connects the and the subunits
The mature insulin hormone consists only of the and chains connected by 2 disulfide links and the third disulfide
bridge in the subunit
Upon insulin release, C peptide is also released
Figure 3. (Pre)proinsulin and insulin molecules
OUTLINE
I. The PancreasII. Insulin
A. Insulin StructureB. Insulin GeneC. Insulin SynthesisD. Insulin SecretionE. Insulin-Nutrient
Feedback
F. In Vivo RelationshipBetween Plasma
Glucose and Insulin
Secretion
G. Biphasic Response toGlucose
H. Stimulants & Inhibitors ofInsulin Secretion
I. Actions of InsulinJ. Effects of Insulin
III.GlucagonA. Glucagon SynthesisB. Regulation of Secretion
IV.SomatostatinA. Somatostatin SynthesisB. Regulation of Secretion
IIII..IINNSSUULLIINN
OS 202C: Endocrine SystemPANCREATIC ISLETS PHYSIOLOGY
Jan 2, 2012
Dr. Cynthia Halili-Manabat
-
8/13/2019 [OS 202C] 20120102 Pancreatic Islet Physiology (Insulin)
2/10
22ooff1100JJAAYYVV,,NNIIKKOO,,PPAAMM PPAANNCCRREEAATTIICCIISSLLEETTSSPPHHYYSSIIOOLLOOGGYY
Preproinsulin contains 4 sequential peptides: N-terminalsignal peptide, chain of insulin, C peptide and chain of
insulin
BB..IINNSSUULLIINNGGEENNEE Composed of 4 exons and 2 introns Directs synthesis of preproinsulin Translation of mature mRNA initiates synthesis in the
ribosomes
Order of synthesis of polypeptide chain: N-terminalsignal peptide, B chain, C chain, A chain
A long polypeptide is formed, allowing it to fold onitself (by disulfide bonds); sequences not needed are
cleaved
CC..IINNSSUULLIINNSSYYNNTTHHEESSIISS
Figure 4. Synthesis of Insulin
Step 1: Insulin gene codes for preproinsulin Step 2: Mature mRNA initiates synthesis of N-terminal signal
peptide (S) in the ribosomes, followed by B,C and A chain
Step 3: The signal is degraded during the course ofcompletion of the proinsulin molecule
Step 4: The latter is folded into a conformation that permitsdisulfide linkages between the A and B chains to form
Step 5: within the Golgi and secretory granules, convertingenzymes cleave off the C chain (C peptide), completing the
synthesis of insulin*
Step 6: insulin molecules are concentrated in the electron-dense core of the granule, whereas C peptides are in the
peripheral halo of the granule
DD..IINNSSUULLIINNSSEECCRREETTIIOONNNotes: Please refer to Figure 5: Insulin Secretion in the appendix. The
step numbers refer to the numbers in the diagram. The premise in the
following sequence is that there is already preformed insulin waiting for
release.
Glucose, more specifically increase in glucose levels, is themost important stimulus for insulin secretion.
oStep 1: Entry of glucose facilitated by GLUT2transportersGLUT2 transportersare concentrated in the microvilli of the
canaliculi between cells
facilitates diffusion of glucose into the cell helps maintain the glucose conc. in the cell at a level that is
essentially equal to that of the interstitial fluid
takes up glucose freelyoStep 2: Glucose undergoes glycolysis; reacts with
glucokinase
Glucokinase is the fundamental glucose sensor that controlsthe subsequent cell response
Has Km for glucose of 5 mM, which is in the physiologicalrange
Phosphorylation of glucose by glucokinase is the first andrate-limiting step in islet glucose use
oStep 3 (and 4): Increase in ATP levels due to glycolysis,leading to increased ATP/ADP ratioBerne: subsequent rate of insulin secretion parallels that of
glucose oxidation)
oStep 5: Closure of ATP-sensitive K+ channelsefflux ofK+ from cell suppressed K accumulates
depolarization in cell cytoplasm
oStep 6: Depolarization of cell cytoplasm opens Ca
++
channels which results in Increased intracellular Ca
++
concentration
oStep 7: Increased intracellular Ca++ concentrationactivates mechanism for secretory granule movement
along the microtubules (the microtubules contract)
secretory granules fuse with cell membrane
exocytosis of insulin
There are other mechanisms of insulin production:oStep 8: Glucagon (and GLP1, -adrenergic)binds to Gsadenyl cyclase Secondary rise in cAMP levels (thru
G-protein linked receptors) stimulates insulin release
by cAMP-dependent protein kinase A mediate
insulin-releasing effects
o-adrenergic receptor stimulation decreasecAMPdecrease insulin secretionoSomatostatin binds to Gi decreases cAMP levels
decreases insulin release
oStep 9: Parasympathetic innervation (vagal stimulationof cells) acetylcholine binds to Gq(note that in
the figure it is Gs; however, Gq is the one that forms
the link in the phosphoinositide signaling system [Voet &
Voet, Biochemistry 3rd
ed.]) phospholipase C IP3
and DAG IP3 increases Ca2+
and DAG stimulates
Special Notes (from 2015 trans)
*Cleavage is done as proinsulin is packaged into granules by Golgi
Apparatus (cleaved here); the enzymes that cleave C-peptide are
proconvertase-1 and carboxypeptidase-H; resultant insulin
molecule, along with C peptide, is retained in the granules and
released by exocytosis in 1:1 ratio
Insulin becomes associated with zinc as the secretory granules
mature; zinc insulin crystals form the dense central core of the
granule, whereas C peptide is present in the clear space between the
granule membrane and core
NOTE: Molar ratio of C-peptide to insulin is 1:1, thus amount of C-
peptide approximates the amount of ENDOGENOUS insulin in the
blood
Measured used to differentiate type I diabetes mellitusversus type II: zero or very low C peptide suggests type I
DM (meaning zero production/total lack of endogenous
insulin)
bodys intrinsic production of insulin cannot be measuredby taking insulin levels in type I DM patients because the
treatment is exogenousinsulin
-
8/13/2019 [OS 202C] 20120102 Pancreatic Islet Physiology (Insulin)
3/10
33ooff1100JJAAYYVV,,NNIIKKOO,,PPAAMM PPAANNCCRREEAATTIICCIISSLLEETTSSPPHHYYSSIIOOLLOOGGYY
protein kinase C increase in calcium and protein
kinase C mediates insulin-releasing effects
oInflux of ketoacids, fatty acids and amino acids resultingin increase intracellular ATP (upper left of diagram)
oSulfonylureas (eg 2nd generation drugs: glibenclamide,glicazide, glimepiride) binds to receptors (SUR) that
forms one component of the K+
channels closes K+
channels causes cytoplasmic depolarization
increase insulin production (right of diagram)
EE..IINNSSUULLIINN--NNUUTTRRIIEENNTTFFEEEEDDBBAACCKK
Figure 6. Feedback Relationship of Insulin and Nutrients
Insulin secretion is governed by a feedback relationship withexogenous nutrient supply
When substrate supply is abundant insulin is secreted inresponse insulin stimulates use of incoming nutrients and
simultaneously inhibits the mobilization of analogous
endogenous substrates
When nutrient supply is low or absent insulin secretion isdampenedmobilization of endogenous fuels is enhanced
FF..IINNVVIIVVOORREELLAATTIIOONNSSHHIIPPBBEETTWWEEEENNPPLLAASSMMAA
GGLLUUCCOOSSEEAANNDDIINNSSUULLIINNSSEECCRREETTIIOONN
Figure 7. Relationship of serum glucose to insulin response
The relationship between plasma insulin and plasma glucoseis sigmoidal.
Virtually no insulin is secreted below a plasma glucosethreshold of about 50 mg/dl
oAt no time, however, will you have insulin at 0 because itmodulates ketogenesis.
oIf insulin is still secreted, hypoglycemia will occur,decreasing available glucose to the braincoma
A half-maximal insulin secretory response occurs at a plasmaglucose level of about 150 mg/dl (normal fasting blood
glucose level: 70-100 mg/dl).
A maximal insulin response occurs at a level of about 300mg/dl.
oExogenous insulin is required for the uptake of excessglucose.
oIn chronically high glucose levels, the maximal responseoccurs until such a time a point of exhaustion is reached
by the pancreatic islet cells, resulting to a decline of
insulin production.
GG..BBIIPPHHAASSIICCRREESSPPOONNSSEETTOOGGLLUUCCOOSSEE
Figure 8. Plasma glucose and insulin responses over time with
a glucose infusion
Phase 1oInitial rapid riseoSurge of insulin due to the release of preformed insulin
stored in the secretory granules in the cells
oLost in diabetic patientsoGoes down after 5-10 minutesoThe part of the graph that follows phase 1, wherein a
steep decrease in insulin level is observed, is due to the
depletion of insulin stored in secretory granules.
Phase 2oContinuous and gradual rise then plateau due to newly-
synthesized insulin from the cells
HH..SSTTIIMMUULLAANNTTSS&&IINNHHIIBBIITTOORRSSOOFFIINNSSUULLIINNSSEECCRREETTIIOONN
Figure 9. Stimulation and inhibition of insulin production and
release
cells
insulin
-
8/13/2019 [OS 202C] 20120102 Pancreatic Islet Physiology (Insulin)
4/10
44ooff1100JJAAYYVV,,NNIIKKOO,,PPAAMM PPAANNCCRREEAATTIICCIISSLLEETTSSPPHHYYSSIIOOLLOOGGYY
Table 2: Stimulants & Inhibitors of Insulin Secretion
Stimulants Inhibitors
Glucose Somatostatin
-inhibits both
insulin and
glucagons
Amino acids (most
potent are arginine
and lysine)
-adrenergic
stimulators
Intestinal hormones
(GLP-1 and GLP-2) -
Anticipates rise in
insulin secretion
-adrenergic
blockers
Ketoacids
-Has minimal effect on
insulin secretion only
when levels of ketone
bodies decrease
-Maintain basal insulin
secretion
Diazoxide
-Keeps K+
channels open
-No depolarization
-No rise in Ca+2
-No insulin
secretion
Acetylcholine Thiazide diuretics- acts on Na-Cl
channel
Glucagon
cAMP
Table 3: Stimulants and Inhibitors of Beta Cells
Stimulants Inhibitors
Direct stimulantsstimulate beta cells
to produce more
insulinoGlucose-
primary
oFatty acidsoAcetylcholineoGlucagonsoAmino acidsoKetonesoGI hormones
**FA and ketones: lower
effect; only permissive
effect since they are
present in state of
starvation; Ach: vagal
stimulation
o Somatostatin (generallyinhibitory in
endocrinology)
o Epinephrineo Norepinephrine (has a
larger effect than
epinephrine)
Indirect stimulantsincrease beta cell
production of insulin
due to the primary
effect of the
hormones of raising
blood glucose levels
oGrowthhormone
oCortisolJ. EFFECTS OF INSULIN
J. EFFECTS OF INSULIN
J. EFFECTS OF INSULIN
INSULIN
II..AACCTTIIOONNSSOOFFIINNSSUULLIINNNotes: Please refer to Figure 10: Actions of Insulin in the appendix.
Primarily anabolic Transport of insulin through the capillary wall- rate-
limiting step
Insulin receptoroin the cell membrane since insulin is a peptide hormoneo2 subunits (extracellular)Bind insulin731 amino acids each
o2 subunits (intracellular)Coupling domain; Have tyrosine kinase domainsIntrinsic enzyme activityHas 194 extracellular residues and 23 amino acid
transmembrane anchor each
oSubunits are bound by disulfide linkages Binding of insulin to the insulin receptor causes activation of
the tyrosine kinase domain
The hormone-receptor complex is subsequently internalizedby endocytosis; the hormone is degraded; and the receptor
is either degraded, stored or recycled back to the plasma
membrane.
Tyrosine kinase phosphorylates Insulin Receptor Substrate(IRS)
Phosphorylated IRS activates PI-3 kinase, whichphosphorylates PI-3 phosphates
PI-3 phosphates cause the translocation and binding of theGLUT-4 transporters from the intracellular pool to the
plasma membrane
Insulin promotes cellular uptake of amino acids, K+, PO4-,and Mg2+
Insulin also affects RNA transcription (mitogenic signals) byacting on Insulin Response Elements (IREs)
Insulin also regulates the action of metabolic enzymesinvolved in glycogenesis, glycolysis, and lipogenesis
Note: Please refer to Figure 11: Levels of Insulin Function in the
appendix.
Levels of insulin actionoLevel 1up to the level of IRSoLevel 2up to the level of kinasesoLevel 3final effects in cell
J. EFF J. EFFECTS OF INSULIN
J. EFFECTS OF INSULIN
J. EFFECTS OF INSULINJ. EFFECTS OF INSULIN
J. EFFECTS OF INSULIN
J. EFFECTS OF INSULIN
J. EFFECTS OF INSULIN
ECTS OF INSU INSULIN
LIN
-
8/13/2019 [OS 202C] 20120102 Pancreatic Islet Physiology (Insulin)
5/10
55ooff1100JJAAYYVV,,NNIIKKOO,,PPAAMM PPAANNCCRREEAATTIICCIISSLLEETTSSPPHHYYSSIIOOLLOOGGYY
JJ..EEFFFFEECCTTSSOOFFIINNSSUULLIINNNote: Please refer to Figure 12: Effects of Insulin in the appendix.
Insulin has mostly anabolic effects on cells Glucose metabolism
o(-) Glucose productiono(-) Plasma glucoseo(+) Glucose oxidationo(+) Storage of glucose as glycogeno(+) glucose transport
Protein uptakeo(-) Plasma amino acids and ketoacidso(+) Protein synthesis
Lipid synthesiso(-) Glucose from livero(-) Mobilization and oxidation of fatty acidso(-) Plasma free fatty acids and glycerolo(+) Uptake in insulin-sensitive tissueso(+) Storage
Growth and gene expression Ion transport Effects on specific tissues
oMuscle(+) Glucose and amino acid uptake(-) Protein breakdownoAdipose tissue(-) Lipolysis and ketogenesis(+) Triglyceride uptakeoLiver(-) Gluconeogenesis and glycogenolysisDecreases the levels or activities of the committed
gluconeogenic enzymes (pyruvate carboxylase,
phosphoenolpyruvate carboxykinase and fructose-1,6-
bisphosphatase)
Inhibits oxidation of fatty acids (Guyton)(+) Glycogenesis and glycolysisPromotes synthesis fatty acids
INSULIN
INSULIN
INSULIN
INSULIN
INSULIN
INSULIN
INSULIN
INSULIN
INSULIN
INSULIN
IIIIII..GGLLUUCCAAGGOONN Increases blood sugar, making energy more availableo Has the opposite effect as insulino Catabolic
Notes: How Glucagon WorksGlucagon binds to glucagon receptor activates G proteins
activates the enzyme adenylate cyclase adenylate
cyclase manufactures cAMP activates cAMP-dependent
enzyme protein kinase A protein kinase A
phosphorylates an enzyme, whihch either stimulates or
inhibitsthe enzyme
Effects inside the liver:o Increases rate of glycogenesis by changing the
intracellular cAMP levels using the G protein mechanism
to activate glycogen phosphorylase via the protein kinase
A path
o Increases hepatic gluconeogenesisby stimulating fructose2, 6-bisphosphatase
o Decreases glycogenesis by deactivating glycogen synthase This step prevents the glucose-1-phosphate released in
glycogenolysis from undergoing resynthesis to glycogen
o Decreases glycolysisby deactivating phosphofructokinaseand pyruvate kinase
o Increases ketogenesis and decreases cholesterolsynthesis, directing free fatty acids away from triglyceride
synthesis and towards -oxidation by inactivating acetly-
CoA carboxylase (which is the enzyme for the rate-limiting
step)
Just to be clear: it's the phosphorylation caused by protein
kinase A that activates the enzymes glycogen phosphorylase
and fructose 2,6-bisphosphatase AND deactivates the
enzymes glycogen synthase, phosphofructokinase, and so on.
Effects outside the livero Increases lypolysis and delivery of free fatty acids to the
liver (by activating adipose tissue lipase)
o Inhibits renal tubular sodium resorption, causingnatriuresis
o Slightly increases cardiac outputo May play a role in regulating the appetite by acting on the
CNS
AA..GGLLUUCCAAGGOONNSSYYNNTTHHEESSIISS Preproglucagon to proglucagon Different processing of the precursors yields different
productso -cells of pancreatic islets: glucagon with GRPP and major
proglucagon fragment
o intestinal L-cells: GLP-1 (glucagon-like peptide-1): stimulates insulin
synthesis and secretion, increases insulin sensitivity,
increases mass of -cells and decreases glucagon
secretion
GLP-2 (glucagon-like peptide 2) Glicentin: stimulation of insulin secretion (though this
effect can be ascribed to glucagon)
In the islets, glucose and insulin inhibit glycogen synthesis byrepressing transcription of the glucagon gene
The direction of the blood flow in the islets (insulin-rich core-cells mantle -cells) facilitates inhibitionIV. Somatostatin
IV. SomatostatinINSULIN
-
8/13/2019 [OS 202C] 20120102 Pancreatic Islet Physiology (Insulin)
6/10
66ooff1100JJAAYYVV,,NNIIKKOO,,PPAAMM PPAANNCCRREEAATTIICCIISSLLEETTSSPPHHYYSSIIOOLLOOGGYY
From 2014 Trans: Baby Scott Ong
1) The primary neuroendocrine inhibitor of prolactin secretion is
dopamine.
2) GH stimulates the liver to produce somatomedin.
3) ACTH stimulates the adrenal gland to secrete cortisol,
aldosterone and androgen.
4) TSH is structurally homologous to LH, FSH and HCG.5) The hormone that decreases plasma glucose is insulin.
6) Hormone that increases plasma glucose levels are glucagon,
cortisol and epinephrine.
7) Hormones that increase following blood loss are arginine
vasopressin or ADH, aldosterone and cortisol.
8) One biological effect of glucagon is stimulation of
gluconeogenesis.
9) A parent with an aldosterone producing adenoma
(hyperaldosteronism) may present with hypokalemia.
10) A patient with hypercortisolemia may present with
hyperglycemia, hypertension and visceral obesity.
BB..RREEGGUULLAATTIIOONNOOFFSSEECCRREETTIIOONN Primarily secreted in regards to glucose deficiency in order to
return the circulating glucose to normal levels
Main target: liver Action: promote glycogenolysis and gluconeogenesis Secretion stimulated by (+):o Low plasma glucose: stimulation of secretion is greater
when insulin is low or absent
o Increased plasma amino acids (especially arginine andalanine): stimulation of secretion is greater when insulin is
low or absent and less when insulin is high
To protect from hypoglycemia after consuming an all-protein meal
Increase in amino acids increases the amount ofsubstrate for gluconeogenesis
o Fastingo Exerciseo Neural mechanisms (vagal stimulation, acetylcholine
release, sympathetic nervous system)
o Stressing factors (infections, burns, major surgery, etc.)o catecholamines: epinephrine and norepinephrineo Vasoactive intestinal peptide (VIP)o Cholecystokinin (CCK)
Secretion inhibited by (-):o Hyperglycemia (though not to the same degree as
hypoglycemia)
o Somatostatino Insulin (via GABA)o Increased ketones and free fatty acids in the bloodo Increased urea production
Overall: insulin vs. cortisol, GH, glucagon, epinephrine andnorepinephrine
How come the blood sugar level is maintained and notlowered after an all-protein meal?
o Absorption of AA Increase in blood AA increasedinsulin secretion decreased plasma glucose
o However, glucagon is also secreted, increasing livergluconeogenesis by using the available AA
Note: Please refer to Figure 13 in Appendix for Glucagon Effects on
Carbohydrate and Fat Metabolism
IV. Somatostatin
IIVV..SSOOMMAATTOOSSTTAATTIINN Primary function: extension of the period of time during
which nutrients are assimilated
Specific functions:o Inhibits both insulin and glucagon secretiono Decreases assimilation rate of all nutrients in the GI tract
by inhibiting:
Motilityin the stomach, duodenum and gall bladder Secretionof HCl, pepsin, gastrin, secretin, and intestinal
juices
Exocrinefunctionof the pancreaso Inhibits gastrin, CCK, secretin, motilin, VIP, gastric
inhibitory polypeptide (GIP), enteroglucagon, thyrotropin-
releasing hormone (TRH) and GH
o Inhibits release of pancreatic hormones: insulin andglucagon
o Decreases rate of gastric emptying and reducescontraction of smooth muscles and blood flow within the
intestine
INote: Please refer to Figure 14 in Appendix for Somatostatin role in
Paracrine Interaction in Pancreatic Islets
Somatostatin
IV. Somatostatin
V. Somatostatin
AA..SSOOMMAATTOOSSTTAATTIINNSSYYNNTTHHEESSIISS Synthesized by the:o D cells of the stomach, duodenum/jejunum and
ileum/colon
o cells of the pancreatic isletso Hypothalamus
Exocytosis is stimulated by cAMP Two types:o
SS 14 (14-amino acid): produced by pancreatic cells;via neurocrine/paracrine secretion directly inhibit
insulin and glucagon responses to meals
o SS 28 (28-amino acid): produced by intestinal cells;released after ingestion of fat; can reach islets via
bloodstream, thereby functioning as a true hormone
RREEGGUULLAATTIIOONNOOFFSSEECCRREETTIIOONN Stimulated by (+):o Glucoseo Amino acidso Free fatty acidso GI hormoneso Glucagono -adrenergic neurotransmitterso Cholinergic neurotransmitters
Inhibited by (-):o Insulino -adrenergic neurotransmitters
Jay-V: Happy New Year 2016! Ang saya ng OS202C, in 3 days
lang, endocrinologist ka na! Chos. Cheers to my co-transers,
windang lang na malaman mong transer ka pala right after ng
lecture. To the person I love the most, hindi mo to mababasa.
Ahahaha. Looking forward for a terrific year with you batch! :D
Niko: I don't have anything to say so please enjoy this smiley
instead. :D
Pam: Brilliant first half day back!
-
8/13/2019 [OS 202C] 20120102 Pancreatic Islet Physiology (Insulin)
7/10
77ooff1100JJAAYYVV,,NNIIKKOO,,PPAAMM PPAANNCCRREEAATTIICCIISSLLEETTSSPPHHYYSSIIOOLLOOGGYY
Figure 5. Insulin Secretion
Figure 10. Actions of Insulin
-
8/13/2019 [OS 202C] 20120102 Pancreatic Islet Physiology (Insulin)
8/10
88ooff1100JJAAYYVV,,NNIIKKOO,,PPAAMM PPAANNCCRREEAATTIICCIISSLLEETTSSPPHHYYSSIIOOLLOOGGYY
Figure 11. Levels of Insulin Action
Figure 12. Effects of Insulin
-
8/13/2019 [OS 202C] 20120102 Pancreatic Islet Physiology (Insulin)
9/10
99ooff1100JJAAYYVV,,NNIIKKOO,,PPAAMM PPAANNCCRREEAATTIICCIISSLLEETTSSPPHHYYSSIIOOLLOOGGYY
Figure 13.Glucagon Effects on Carbohydrate and Fat Metabolism
Figure 14.Paracrine Interaction of Pancreatic Islets
-
8/13/2019 [OS 202C] 20120102 Pancreatic Islet Physiology (Insulin)
10/10
1100ooff1100JJAAYYVV,,NNIIKKOO,,PPAAMM PPAANNCCRREEAATTIICCIISSLLEETTSSPPHHYYSSIIOOLLOOGGYY
From 2013:
Table 4. Summary of Metabolic Hormones Controlling the Overall Flow of Fuels
Liver Muscle Adipose Tissue
Insulin + glycogen synthesis + glycolysis - glycogenolysis - gluconeogenesis - ketogenesis
+ glucose uptake + amino acid uptake - proteolysis
+ glucose uptake + free fatty acid uptake - lipolysis
Glucagon + glycogenolysis + gluconeogenesis + ketogenesis
minimal action minimal action
Cortisol + glycogenolysis + gluconeogenesis -amino acid uptake +proteolysis
- insulin action + lipolysis - insulin action
Growth Hormone + gluconeogenesis + IGFS/IGFBP + amino acid uptake - glucose uptake + lipolysis - glucose uptake
Epinephrine + glycogenolysis + gluconeogenesis +ketogenesis
+ glycogenolysis - insulin action + lipolysis - insulin action
Thyroid Hormone +gluconeogenesis + proteolysis + lipolysis