insulin and the brainpages.ucsd.edu/~mboyle/cogs163/pdf-files/s18-01-insulin and the b… · the...
TRANSCRIPT
![Page 1: Insulin and the brainpages.ucsd.edu/~mboyle/COGS163/pdf-files/S18-01-Insulin and the b… · The neural terminal is said to be composed of nerve fibers and interstitial Cajal’scells](https://reader033.vdocument.in/reader033/viewer/2022050403/5f8083e3abf6e84a885c13f2/html5/thumbnails/1.jpg)
Insulin and the brain
Mary ET Boyle + Billy + Bree + Alex + RachaelDepartment of Cognitive Science, UCSD
![Page 2: Insulin and the brainpages.ucsd.edu/~mboyle/COGS163/pdf-files/S18-01-Insulin and the b… · The neural terminal is said to be composed of nerve fibers and interstitial Cajal’scells](https://reader033.vdocument.in/reader033/viewer/2022050403/5f8083e3abf6e84a885c13f2/html5/thumbnails/2.jpg)
1921 Banting & Macleod
Nobel Prize1923
White, M. F. (2003) Science
![Page 3: Insulin and the brainpages.ucsd.edu/~mboyle/COGS163/pdf-files/S18-01-Insulin and the b… · The neural terminal is said to be composed of nerve fibers and interstitial Cajal’scells](https://reader033.vdocument.in/reader033/viewer/2022050403/5f8083e3abf6e84a885c13f2/html5/thumbnails/3.jpg)
Berg, J. M., Tymoczko, J. L. and Stryer, L. (2007) Biochemistry 6 Ed.; WH Freeman, NY
![Page 4: Insulin and the brainpages.ucsd.edu/~mboyle/COGS163/pdf-files/S18-01-Insulin and the b… · The neural terminal is said to be composed of nerve fibers and interstitial Cajal’scells](https://reader033.vdocument.in/reader033/viewer/2022050403/5f8083e3abf6e84a885c13f2/html5/thumbnails/4.jpg)
Berg, J. M., Tymoczko, J. L. and Stryer, L. (2007) Biochemistry 6 Ed.; WH Freeman, NY
![Page 5: Insulin and the brainpages.ucsd.edu/~mboyle/COGS163/pdf-files/S18-01-Insulin and the b… · The neural terminal is said to be composed of nerve fibers and interstitial Cajal’scells](https://reader033.vdocument.in/reader033/viewer/2022050403/5f8083e3abf6e84a885c13f2/html5/thumbnails/5.jpg)
![Page 6: Insulin and the brainpages.ucsd.edu/~mboyle/COGS163/pdf-files/S18-01-Insulin and the b… · The neural terminal is said to be composed of nerve fibers and interstitial Cajal’scells](https://reader033.vdocument.in/reader033/viewer/2022050403/5f8083e3abf6e84a885c13f2/html5/thumbnails/6.jpg)
Pancreas basics
splenic vein
Images adapted from: Kapit. W. et al., (1987) The Physiology Coloring Book, Harper Collins, NY; http://teachmeanatomy.info/
pancreatic duct
exocrine ‐ acinus
δ‐cellssomatostatin
β‐cellsinsulin& amylin
α‐cellsglucagon
F‐cellspancreatic polypeptide
ε‐cellsghrelin
![Page 7: Insulin and the brainpages.ucsd.edu/~mboyle/COGS163/pdf-files/S18-01-Insulin and the b… · The neural terminal is said to be composed of nerve fibers and interstitial Cajal’scells](https://reader033.vdocument.in/reader033/viewer/2022050403/5f8083e3abf6e84a885c13f2/html5/thumbnails/7.jpg)
Cell Hormone Function
α‐cells(15%)
glucagon stimulate gluconeogenesis and release of glucose into blood stream
β‐cells(75%)
insulin & amylin responsible for decreasing blood glucose levels and satiety (insulin 100:amylin 1)
δ‐cells(5%)
somatostatin inhibition of insulin and glucagon secretion
ε‐cells(<1%)
ghrelin stimulating appetite hormone
F‐cells(<5%)
pancreatic polypeptide
self‐regulate exocrine and endocrine pancreatic secretions
Cell types in the islets of Langerhans:
Berg, J. M., Tymoczko, J. L. and Stryer, L. (2007) Biochemistry 6 Ed.; WH Freeman, NY
![Page 8: Insulin and the brainpages.ucsd.edu/~mboyle/COGS163/pdf-files/S18-01-Insulin and the b… · The neural terminal is said to be composed of nerve fibers and interstitial Cajal’scells](https://reader033.vdocument.in/reader033/viewer/2022050403/5f8083e3abf6e84a885c13f2/html5/thumbnails/8.jpg)
Insulin and glucagon are complementary
Images adapted from: Kapit. W. et al., (1987) The Physiology Coloring Book, Harper Collins, NY
![Page 9: Insulin and the brainpages.ucsd.edu/~mboyle/COGS163/pdf-files/S18-01-Insulin and the b… · The neural terminal is said to be composed of nerve fibers and interstitial Cajal’scells](https://reader033.vdocument.in/reader033/viewer/2022050403/5f8083e3abf6e84a885c13f2/html5/thumbnails/9.jpg)
Insulin reduces blood glucose levels by activating glucose transporters (GLUT) enabling the uptake of glucose in:
β‐cells
Glucose sensor (GLUT2)
insulin
Glucose transporter(GLUT4)
Insulinreceptor
Cell metabolism
Glycogensynthesis
Glycogensynthesis
Proteinsynthesis
Fatty Acidsynthesis
Glycerol
Triglycerides
High levels of glucoseIn blood
Images adapted from: Kapit. W. et al., (1987) The Physiology Coloring Book, Harper Collins, NY
![Page 10: Insulin and the brainpages.ucsd.edu/~mboyle/COGS163/pdf-files/S18-01-Insulin and the b… · The neural terminal is said to be composed of nerve fibers and interstitial Cajal’scells](https://reader033.vdocument.in/reader033/viewer/2022050403/5f8083e3abf6e84a885c13f2/html5/thumbnails/10.jpg)
Insulin reduces circulating glucose by activating glucose transporters on cell membrane, enabling the uptake of glucose into most peripheral tissues where the glucose is used as a fuel or stored as glycogen.
In muscles, binding increases glucose entry (5) which is either oxidized for energy (6) or stored as glycogen(9), protein (10) and fatty acids (11). The fatty acids are used in liver and sent to fat cells (12). In fat cells, insulin promotes entry, enhancing its conversion to glycerol and fatty acids. These esterify to form triglycerides (13), which are stored.
![Page 11: Insulin and the brainpages.ucsd.edu/~mboyle/COGS163/pdf-files/S18-01-Insulin and the b… · The neural terminal is said to be composed of nerve fibers and interstitial Cajal’scells](https://reader033.vdocument.in/reader033/viewer/2022050403/5f8083e3abf6e84a885c13f2/html5/thumbnails/11.jpg)
![Page 12: Insulin and the brainpages.ucsd.edu/~mboyle/COGS163/pdf-files/S18-01-Insulin and the b… · The neural terminal is said to be composed of nerve fibers and interstitial Cajal’scells](https://reader033.vdocument.in/reader033/viewer/2022050403/5f8083e3abf6e84a885c13f2/html5/thumbnails/12.jpg)
![Page 13: Insulin and the brainpages.ucsd.edu/~mboyle/COGS163/pdf-files/S18-01-Insulin and the b… · The neural terminal is said to be composed of nerve fibers and interstitial Cajal’scells](https://reader033.vdocument.in/reader033/viewer/2022050403/5f8083e3abf6e84a885c13f2/html5/thumbnails/13.jpg)
![Page 14: Insulin and the brainpages.ucsd.edu/~mboyle/COGS163/pdf-files/S18-01-Insulin and the b… · The neural terminal is said to be composed of nerve fibers and interstitial Cajal’scells](https://reader033.vdocument.in/reader033/viewer/2022050403/5f8083e3abf6e84a885c13f2/html5/thumbnails/14.jpg)
Nervous system divisions:
Nervous system
Central Nervous System Peripheral Nervous System
Autonomic Nervous system
Parasympathetic nervous system
Sympathetic nervous system
Enteric nervous system
Slowly activated dampening system
![Page 15: Insulin and the brainpages.ucsd.edu/~mboyle/COGS163/pdf-files/S18-01-Insulin and the b… · The neural terminal is said to be composed of nerve fibers and interstitial Cajal’scells](https://reader033.vdocument.in/reader033/viewer/2022050403/5f8083e3abf6e84a885c13f2/html5/thumbnails/15.jpg)
Sympathetic‐Fight or
Flight Mode
Lower levels of insulin – leaves more glucose in the blood for fighting or “flight‐ing”
![Page 16: Insulin and the brainpages.ucsd.edu/~mboyle/COGS163/pdf-files/S18-01-Insulin and the b… · The neural terminal is said to be composed of nerve fibers and interstitial Cajal’scells](https://reader033.vdocument.in/reader033/viewer/2022050403/5f8083e3abf6e84a885c13f2/html5/thumbnails/16.jpg)
Autonomic Nervous System Control of insulin release:
parasympatheticceliac
ganglion
Lateral hypothalamus
Ventromedial hypothalamus
sympathetic
parasympathetic
superior mesenteric ganglion
Kiba, T (2004) Pancreas, Vol 29
![Page 17: Insulin and the brainpages.ucsd.edu/~mboyle/COGS163/pdf-files/S18-01-Insulin and the b… · The neural terminal is said to be composed of nerve fibers and interstitial Cajal’scells](https://reader033.vdocument.in/reader033/viewer/2022050403/5f8083e3abf6e84a885c13f2/html5/thumbnails/17.jpg)
Anatomy of the ANS
Slide from Lu Chen
![Page 18: Insulin and the brainpages.ucsd.edu/~mboyle/COGS163/pdf-files/S18-01-Insulin and the b… · The neural terminal is said to be composed of nerve fibers and interstitial Cajal’scells](https://reader033.vdocument.in/reader033/viewer/2022050403/5f8083e3abf6e84a885c13f2/html5/thumbnails/18.jpg)
Anatomy of the ANS
Slide from Lu Chen
![Page 19: Insulin and the brainpages.ucsd.edu/~mboyle/COGS163/pdf-files/S18-01-Insulin and the b… · The neural terminal is said to be composed of nerve fibers and interstitial Cajal’scells](https://reader033.vdocument.in/reader033/viewer/2022050403/5f8083e3abf6e84a885c13f2/html5/thumbnails/19.jpg)
Insulin Secretion from Beta Cells 1.) Close K+ channels ‐> depolarization ‐> Activation of Calcium channels ‐> Calcium influx ‐> insulin containing vesicle exocytosis
2.) Activate adenylate cyclase ‐> increase cAMP ‐> activation of PKA ‐> insulin containing vesicle exocytosis
3.) Activate PLC ‐> PIP2 to IP3 and DAG ‐> IP3 increases calcium and DAG activates PKC ‐> both cause insulin secretion via exocytosis
4.) Activate PLA2 ‐> converts phospholipids to arachidonic acid ‐> AAs cause insulin release via exocytosis
![Page 20: Insulin and the brainpages.ucsd.edu/~mboyle/COGS163/pdf-files/S18-01-Insulin and the b… · The neural terminal is said to be composed of nerve fibers and interstitial Cajal’scells](https://reader033.vdocument.in/reader033/viewer/2022050403/5f8083e3abf6e84a885c13f2/html5/thumbnails/20.jpg)
![Page 21: Insulin and the brainpages.ucsd.edu/~mboyle/COGS163/pdf-files/S18-01-Insulin and the b… · The neural terminal is said to be composed of nerve fibers and interstitial Cajal’scells](https://reader033.vdocument.in/reader033/viewer/2022050403/5f8083e3abf6e84a885c13f2/html5/thumbnails/21.jpg)
![Page 22: Insulin and the brainpages.ucsd.edu/~mboyle/COGS163/pdf-files/S18-01-Insulin and the b… · The neural terminal is said to be composed of nerve fibers and interstitial Cajal’scells](https://reader033.vdocument.in/reader033/viewer/2022050403/5f8083e3abf6e84a885c13f2/html5/thumbnails/22.jpg)
![Page 23: Insulin and the brainpages.ucsd.edu/~mboyle/COGS163/pdf-files/S18-01-Insulin and the b… · The neural terminal is said to be composed of nerve fibers and interstitial Cajal’scells](https://reader033.vdocument.in/reader033/viewer/2022050403/5f8083e3abf6e84a885c13f2/html5/thumbnails/23.jpg)
![Page 24: Insulin and the brainpages.ucsd.edu/~mboyle/COGS163/pdf-files/S18-01-Insulin and the b… · The neural terminal is said to be composed of nerve fibers and interstitial Cajal’scells](https://reader033.vdocument.in/reader033/viewer/2022050403/5f8083e3abf6e84a885c13f2/html5/thumbnails/24.jpg)
unconditioned stimulus: insulin
unconditioned response:
hypoglycemic saline
odor
conditioned response:
hypoglycemic
neutral stimulus:odor
Begg, D. P and Woods, S. C. (2013) Adv Physiol. Educ 37: 53‐60
insulin secretion could be
conditioned reflex
Note: For this experiment a non‐physiological level of insulin was injected.
![Page 25: Insulin and the brainpages.ucsd.edu/~mboyle/COGS163/pdf-files/S18-01-Insulin and the b… · The neural terminal is said to be composed of nerve fibers and interstitial Cajal’scells](https://reader033.vdocument.in/reader033/viewer/2022050403/5f8083e3abf6e84a885c13f2/html5/thumbnails/25.jpg)
autonomic and endocrine response not related to
nutrient absorption.
humans: increase in ciruculating insulin in response to eating imaginary food
(hypnosis)
sight, smell and expectation of
food
cephalic phase is also subject to
being conditioned
Cephalic phase of insulin secretion:
Ahren, B. (2000) Diabetologia 43: 393–410
“A rapid increase in circulating insulinafter oral glucose,
before
any increase in circulating glucose, has been shown in normal subjects.”
![Page 26: Insulin and the brainpages.ucsd.edu/~mboyle/COGS163/pdf-files/S18-01-Insulin and the b… · The neural terminal is said to be composed of nerve fibers and interstitial Cajal’scells](https://reader033.vdocument.in/reader033/viewer/2022050403/5f8083e3abf6e84a885c13f2/html5/thumbnails/26.jpg)
Blocking vagus nerve input abolishes cephalic phase of insulin release:
Ahren, B. (2000) Diabetologia 43: 393–410
trimetophane (trimethaphane) blocks the descending parasympathetic activity
nicotinic receptor blocker.
![Page 27: Insulin and the brainpages.ucsd.edu/~mboyle/COGS163/pdf-files/S18-01-Insulin and the b… · The neural terminal is said to be composed of nerve fibers and interstitial Cajal’scells](https://reader033.vdocument.in/reader033/viewer/2022050403/5f8083e3abf6e84a885c13f2/html5/thumbnails/27.jpg)
the importance of the cephalic phase of insulin response:
1‐3% of the total insulin released after a meal is associated with the cephalic phase
glucose intolerant without cephalic
phase
amount of insulin secreted during cephalic
phase is inversely related to circulating
glucose
insulin administration right after food intake improves glucose tolerance in obese
and type 2 diabetic individuals
insulin released during cephalic
phase
circulating glucose
Ahren, B. (2000) Diabetologia 43: 393–410
looks diabetic!
![Page 28: Insulin and the brainpages.ucsd.edu/~mboyle/COGS163/pdf-files/S18-01-Insulin and the b… · The neural terminal is said to be composed of nerve fibers and interstitial Cajal’scells](https://reader033.vdocument.in/reader033/viewer/2022050403/5f8083e3abf6e84a885c13f2/html5/thumbnails/28.jpg)
![Page 29: Insulin and the brainpages.ucsd.edu/~mboyle/COGS163/pdf-files/S18-01-Insulin and the b… · The neural terminal is said to be composed of nerve fibers and interstitial Cajal’scells](https://reader033.vdocument.in/reader033/viewer/2022050403/5f8083e3abf6e84a885c13f2/html5/thumbnails/29.jpg)
Tissue Distribution of glucose transporters
Berg, J. M., Tymoczko, J. L. and Stryer, L. (2007) Biochemistry 6 Ed.; WH Freeman, NY
![Page 30: Insulin and the brainpages.ucsd.edu/~mboyle/COGS163/pdf-files/S18-01-Insulin and the b… · The neural terminal is said to be composed of nerve fibers and interstitial Cajal’scells](https://reader033.vdocument.in/reader033/viewer/2022050403/5f8083e3abf6e84a885c13f2/html5/thumbnails/30.jpg)
Actions of glucagon:
Low levels of glucose in blood
Detect glucose levels
Glycogentree
Glucagonreceptors
After glucagon binds to its receptors on the liver cells,
There is an increase in cyclic‐AMP within hepatocytes.
cAMP activates a cascade of enzymes degrading glycogen into
glucose.
Glycogenolysis = breakdown of glycogenGluconeogenesis = synthesis of glucose from amino acids in the liver
glycogen phosphorylase
Images adapted from: Kapit. W. et al., (1987) The Physiology Coloring Book, Harper Collins, NY
![Page 31: Insulin and the brainpages.ucsd.edu/~mboyle/COGS163/pdf-files/S18-01-Insulin and the b… · The neural terminal is said to be composed of nerve fibers and interstitial Cajal’scells](https://reader033.vdocument.in/reader033/viewer/2022050403/5f8083e3abf6e84a885c13f2/html5/thumbnails/31.jpg)
Glucose Tolerance Test:
Images adapted from: Kapit. W. et al., (1987) The Physiology Coloring Book, Harper Collins, NY
![Page 32: Insulin and the brainpages.ucsd.edu/~mboyle/COGS163/pdf-files/S18-01-Insulin and the b… · The neural terminal is said to be composed of nerve fibers and interstitial Cajal’scells](https://reader033.vdocument.in/reader033/viewer/2022050403/5f8083e3abf6e84a885c13f2/html5/thumbnails/32.jpg)
Insulin deficiency
Glucose entry is blocked
Cells utilize their own stores of glycogen
Fat
Protein
Excessive fatty acid utilization leads to formation of ketone
bodies by liver
proteinglycogen
fat
Ketone bodies Hyperphagia
Images adapted from: Kapit. W. et al., (1987) The Physiology Coloring Book, Harper Collins, NY
![Page 33: Insulin and the brainpages.ucsd.edu/~mboyle/COGS163/pdf-files/S18-01-Insulin and the b… · The neural terminal is said to be composed of nerve fibers and interstitial Cajal’scells](https://reader033.vdocument.in/reader033/viewer/2022050403/5f8083e3abf6e84a885c13f2/html5/thumbnails/33.jpg)
Kidney tubules cannot reabsorb the excess filtered glucose.
The extra glucose spills over in urine
(glycosuria)
The excess glucose causes osmotic diuresis (polyuria). Polyuria reduces plasma water, leading to excessive
thirst (polydipsia).
KetonuriaPolyuria
Glycosuria Images adapted from: Kapit. W. et al., (1987) The Physiology Coloring Book, Harper Collins, NY
![Page 34: Insulin and the brainpages.ucsd.edu/~mboyle/COGS163/pdf-files/S18-01-Insulin and the b… · The neural terminal is said to be composed of nerve fibers and interstitial Cajal’scells](https://reader033.vdocument.in/reader033/viewer/2022050403/5f8083e3abf6e84a885c13f2/html5/thumbnails/34.jpg)
Historically, there was little interest in insulin and the brain because:
Begg, D. P and Woods, S. C. (2013) Adv Physiol. Educ 37: 53‐60
“unlike [skeletal muscle], the brain does not require insulin to
take up glucose
brain was considered to be
insulin independent
insulin was considered too large to cross the blood brain barrier”
![Page 35: Insulin and the brainpages.ucsd.edu/~mboyle/COGS163/pdf-files/S18-01-Insulin and the b… · The neural terminal is said to be composed of nerve fibers and interstitial Cajal’scells](https://reader033.vdocument.in/reader033/viewer/2022050403/5f8083e3abf6e84a885c13f2/html5/thumbnails/35.jpg)
Innervation of islet of Langerhans“From the large nerve trunk at one pole of the islet emerges the peri‐insular plexus, the peri‐insular ganglia (p.i.g.), and the “neural terminal” net in and around the islet.
The neural terminal is said to be composed of nerve fibers and interstitial Cajal’s cells (in black).
Part of the islet has been excised to show the interior structure of the islet. c capillary, 800.”
Image adapted from Honjin, 1956; courtesy of John Wiley & Sons, Inc) Durant, s. et al (2003) LABORATORY INVESTIGATION, Vol. 83, No.
![Page 36: Insulin and the brainpages.ucsd.edu/~mboyle/COGS163/pdf-files/S18-01-Insulin and the b… · The neural terminal is said to be composed of nerve fibers and interstitial Cajal’scells](https://reader033.vdocument.in/reader033/viewer/2022050403/5f8083e3abf6e84a885c13f2/html5/thumbnails/36.jpg)
Autonomic Nervous System Control of insulin release:
parasympatheticceliac
ganglion
Lateral hypothalamus
Ventromedial hypothalamus
sympathetic
parasympathetic
superior mesenteric ganglion
Kiba, T (2004) Pancreas, Vol 29
![Page 37: Insulin and the brainpages.ucsd.edu/~mboyle/COGS163/pdf-files/S18-01-Insulin and the b… · The neural terminal is said to be composed of nerve fibers and interstitial Cajal’scells](https://reader033.vdocument.in/reader033/viewer/2022050403/5f8083e3abf6e84a885c13f2/html5/thumbnails/37.jpg)
Lustig RH (2006) Childhood obesity: behavioral aberration or biochemical drive? reinterpreting the first law of thermodynamics Nat Clin Pract Endocrino Metabol 2: 447–458 doi:10.1038/ncpendmet0220
Figure 1 The homeostatic pathway of energy balance
Reproduced with permission from Lustig RH (2001) The neuroendocrinology of childhood obesity.Pediatr Clin North Am 48: 909–930. © (2001) Elsevier Inc.
Pathways:afferent (blue), central (brown), and efferent (white)
![Page 38: Insulin and the brainpages.ucsd.edu/~mboyle/COGS163/pdf-files/S18-01-Insulin and the b… · The neural terminal is said to be composed of nerve fibers and interstitial Cajal’scells](https://reader033.vdocument.in/reader033/viewer/2022050403/5f8083e3abf6e84a885c13f2/html5/thumbnails/38.jpg)
parasympathetic
sympathetic
sensory
isletsB
F
A
D
Insulin/Amylin
Glucagon
Pancreatic Polypeptide
Somatostatin
Kiba, T (2004) Pancreas, Vol 29 ; Ahren, B. (2000) Diabetologia 43: 393–410
![Page 39: Insulin and the brainpages.ucsd.edu/~mboyle/COGS163/pdf-files/S18-01-Insulin and the b… · The neural terminal is said to be composed of nerve fibers and interstitial Cajal’scells](https://reader033.vdocument.in/reader033/viewer/2022050403/5f8083e3abf6e84a885c13f2/html5/thumbnails/39.jpg)
Parasympathetic nerve input:
AChGRPPACAPVIP
B F A D
ACh: acetylcholineGRP: gastrin releasing polypeptide VIP: vasoactive intestinal polypeptidePACAP: pituitary adenylate cyclase activating polypeptide
Kiba, T (2004) Pancreas, Vol 29 ; Ahren, B. (2000) Diabetologia 43: 393–410
![Page 40: Insulin and the brainpages.ucsd.edu/~mboyle/COGS163/pdf-files/S18-01-Insulin and the b… · The neural terminal is said to be composed of nerve fibers and interstitial Cajal’scells](https://reader033.vdocument.in/reader033/viewer/2022050403/5f8083e3abf6e84a885c13f2/html5/thumbnails/40.jpg)
ACh: acetylcholineGRP: gastrin releasing polypeptide
VIP: vasoactive intestinal polypeptidePACAP: pituitary adenylate cyclase activating polypeptide
Parasympathetic nerve input: B F A D
ACh –insulin release
VIP & PACAP –glucose dependent insulin release
GRP – may be involved in neuroregulation
βGLUT2
Vagus Nervestimulation
ACh – releases:glucagonsomatostatin
α,δ
PP – is released by para‐sympathetic activity
F
Kiba, T (2004) Pancreas, Vol 29 ; Ahren, B. (2000) Diabetologia 43: 393–410
![Page 41: Insulin and the brainpages.ucsd.edu/~mboyle/COGS163/pdf-files/S18-01-Insulin and the b… · The neural terminal is said to be composed of nerve fibers and interstitial Cajal’scells](https://reader033.vdocument.in/reader033/viewer/2022050403/5f8083e3abf6e84a885c13f2/html5/thumbnails/41.jpg)
Sympathetic nerve input:
NANPYGalanin
B F A D
NPY: Neuropeptide YNA: Noradrenalin
Kiba, T (2004) Pancreas, Vol 29 ; Ahren, B. (2000) Diabetologia 43: 393–410
![Page 42: Insulin and the brainpages.ucsd.edu/~mboyle/COGS163/pdf-files/S18-01-Insulin and the b… · The neural terminal is said to be composed of nerve fibers and interstitial Cajal’scells](https://reader033.vdocument.in/reader033/viewer/2022050403/5f8083e3abf6e84a885c13f2/html5/thumbnails/42.jpg)
NA: NoradrenalineNPY: Neuropeptide Y
Sympathetic nerve input: B F A D
NA –inhibits glucose dependent insulin release
NPY & Galanin–inhibit insulin release
βsplanchnic nerve
stimulation
NA– releases glucagonand PP
α,F
NA – inhibits somatostatinrelease
δ
Kiba, T (2004) Pancreas, Vol 29 ; Ahren, B. (2000) Diabetologia 43: 393–410
![Page 43: Insulin and the brainpages.ucsd.edu/~mboyle/COGS163/pdf-files/S18-01-Insulin and the b… · The neural terminal is said to be composed of nerve fibers and interstitial Cajal’scells](https://reader033.vdocument.in/reader033/viewer/2022050403/5f8083e3abf6e84a885c13f2/html5/thumbnails/43.jpg)
Other & sensory nerve input:
Sensory nerve CGRPSP
B F A D
CCK: cholecystokininNO: nitric oxideSP: Substance PCGRP: Calcitonin gene‐related polypeptide
Other nerveCCKNO
Kiba, T (2004) Pancreas, Vol 29 ; Ahren, B. (2000) Diabetologia 43: 393–410
![Page 44: Insulin and the brainpages.ucsd.edu/~mboyle/COGS163/pdf-files/S18-01-Insulin and the b… · The neural terminal is said to be composed of nerve fibers and interstitial Cajal’scells](https://reader033.vdocument.in/reader033/viewer/2022050403/5f8083e3abf6e84a885c13f2/html5/thumbnails/44.jpg)
CGRP: Calcitonin Gene‐related peptideSP: Substance P
Sensory nerve input: B F A D
CGRP–inhibits insulin release
CGRP – involved with Amylin
SP – reported to increase and decrease insulin secretion
β
Sensory nerve stimulation
CGRP–stimulates glucagon release
α
CGRP is thought to exert a tonic inhibition of insulin secretion.Kiba, T (2004) Pancreas, Vol 29 ; Ahren, B. (2000) Diabetologia 43: 393–410
![Page 45: Insulin and the brainpages.ucsd.edu/~mboyle/COGS163/pdf-files/S18-01-Insulin and the b… · The neural terminal is said to be composed of nerve fibers and interstitial Cajal’scells](https://reader033.vdocument.in/reader033/viewer/2022050403/5f8083e3abf6e84a885c13f2/html5/thumbnails/45.jpg)
CCK: CholecystokininNO: Nitric Oxide
Other nerve input: B F A D
CCK–stimulates insulin release
NO– inhibition of NO‐synthase inhibits insulin release (mice)
Entero‐pancreatic neuroregulation from the duodenum
β
Other nerve stimulation
Kiba, T (2004) Pancreas, Vol 29 ; Ahren, B. (2000) Diabetologia 43: 393–410
![Page 46: Insulin and the brainpages.ucsd.edu/~mboyle/COGS163/pdf-files/S18-01-Insulin and the b… · The neural terminal is said to be composed of nerve fibers and interstitial Cajal’scells](https://reader033.vdocument.in/reader033/viewer/2022050403/5f8083e3abf6e84a885c13f2/html5/thumbnails/46.jpg)
Ahren, B. (2000) Diabetologia 43: 393–410
![Page 47: Insulin and the brainpages.ucsd.edu/~mboyle/COGS163/pdf-files/S18-01-Insulin and the b… · The neural terminal is said to be composed of nerve fibers and interstitial Cajal’scells](https://reader033.vdocument.in/reader033/viewer/2022050403/5f8083e3abf6e84a885c13f2/html5/thumbnails/47.jpg)
Kiba, T. Pancreas • Volume 29, Number 2, August 2004