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ENDOCRINE SURGERY
Fig. 35.1. Development of dorsal and ventral pancreatic buds at 4 weeks.
Fig. 35.2. Embryonic development of the pancreas. (A) Formation of dorsal and ventral pancreatic buds. (B) Fusion of dorsal
and ventral pancreatic buds to form a single organ.
461
PANCREAS
differentiate into two types of precursor cells
[1]. One precursor cell type differentiates into
glucagon producing alpha cells and PP (F cells)
cells which produce pancreatic polypeptide.
The other precursor cell differentiates into
beta and delta cells, which secrete insulin and
somatostatin respectively. Beta and delta cells
are distributed evenly throughout the pancreas
whereas alpha cells are located more in the
body and tail. PP cells are mainly located in
the posterior head [3].
Developmental Anomalies
of the Pancreas
The complex sequence of events that take place
during pancreatic development allows for the
occurrence of variations as well as anomalies.
Errors in the critical steps of rotation and fusion
produce an annular pancreas or pancreas divisum. Failure or incomplete anastomosis of the
ducts results in multiple variations in major and
minor duct anatomy.
Pancreas Divisum is the most common pancreatic anomaly (10%) [4] and is considered
more of an anatomic variation. It occurs when
the dorsal and ventral pancreatic buds fail to
fuse or fuse incompletely. In this instance, the
smaller duct of Santorini drains the majority of
the pancreas. It was previously hypothesized
that pancreas divisum increased the risk of pancreatitis, as a result of a more frequent functional obstruction of the duct of Santorini. This
however has not been substantiated by large
studies where the incidence of pancreatitis in
pancreas divisum was similar to that of the
general population [4, 5].
Annular pancreas occurs when a band of normal pancreatic tissue extends from the head of
the pancreas and completely encircles the second
portion of the duodenum. It has an estimated
incidence of 1 per 20,000 and 50% of patients
will present with duodenal obstruction at birth or
during the first year of life [6]. The exact manner
in which an annular pancreas forms is unknown.
One theory is that the ring results from hypertrophy of the left portion of the ventral bud,
which then grows in opposition to the right portion of the ventral bud. This results in the formation of a constricting ring around the duodenum.
It has also been postulated that the ring results
from the terminal segment of a single ventral
pancreatic bud adhering to and encircling the
duodenal wall [7].
Aplasia and hypoplasia: The complete
absence of the pancreas is a rare and fatal
event [7]. In the absence of insulin, intrauterine
growth retardation occurs and symptoms of
malabsorption and diabetes mellitus manifest
at birth [8]. Hypoplasia, on the other hand,
involves a partial agenesis of the pancreas
usually involving the dorsal pancreatic bud.
Unlike pancreatic aplasia, both endocrine and
exocrine functions are typically preserved.
Ectopic pancreas occurs when normally differentiated pancreatic tissue develops outside the
pancreas, usually within the gastrointestinal
tract. This is typically found incidentally at endoscopy, surgery, or on autopsy. Ectopic tissue is
commonly located in the stomach, duodenum,
jejunum, or within a Meckel’s diverticulum. It
occurs less frequently in the ileum, liver, spleen,
biliary tract, mesentery, and umbilicus. Ectopic
pancreas within the gastrointestinal tract is
usually asymptomatic, however may result in
ulcerations and GI bleeding [7]. Ectopic pancreatic tissue is thought to arise within the gastrointestinal tract from pluripotent endodermal cells
of the foregut.
Anatomy of the Pancreas
The pancreas is a coarsely lobulated, elongated
gland located in the retroperitoneum of the
upper abdomen. It possesses both endocrine
and exocrine functions vital to glucose homeostasis and nutrient digestion. On average the
pancreas measures 15–20 cm in length, is about
3 cm wide, and has a thickness of about
1–1.5 cm. In an adult the average weight is
75–100 g. It can be divided into five areas: the
head, uncinate process, neck, body, and tail
(Fig. 35.3). The head of the pancreas lies within
the inner curvature of the duodenum. It is
directly anterior to the inferior vena cava and
in proximity to the hilum of the right kidney,
renal, and gonadal vessels. It is covered anteriorly with peritoneum, with the inflection of
the transverse mesocolon passing midway
through the head and along the inferior border
of the body. The lower portion of the pancreatic
head forms the uncinate process, which extends
to the left and lies superior to the third portion
462
ENDOCRINE SURGERY
Fig. 35.3. Anatomy of the pancreas.
of the duodenum and posterior to the superior
mesenteric vessels. The neck is a 2-cm portion
which lies anterior to the formation of the portal
vein. It joins the body which runs to the left and
slightly upward along the posterior abdominal
wall at the level of L1-L2. Posterior to the body is
the aorta and the origin of the superior mesenteric artery. Also lying posteriorly are the left
kidney, renal vessels, and the left adrenal gland.
The body narrows into the relatively mobile tail
which terminates at the hilum of the spleen
within the splenorenal ligament.
Peritoneal Attachments
The pancreas lies within the lesser sac (omental
bursa), covered anteriorly by peritoneum that is
continuous with the peritoneal coverings of the
posterior stomach and the anterior duodenum.
The peritoneal attachment of the transverse
mesocolon forms a double layer and usually
runs along the inferior border of the body. Posterior to the body the middle colic artery originates from the superior mesenteric artery and
runs forward to travel between the layers of the
transverse mesocolon. The posterior pancreatic
surface has no peritoneal covering. At the tail of
the pancreas, the peritoneal reflection forms the
splenorenal ligament.
Pancreatic Ducts
The main pancreatic duct (duct of Wirsung)
runs axially through the pancreatic parenchyma
midway between the superior and the inferior
border and closer to the posterior than anterior
surface. It begins in the tail and passes through
the body, down to the neck, and then to the head
where it meets the common bile duct forming
the ampulla of Vater. The ampulla of Vater then
enters the posteromedial wall of the second part
of the duodenum through the major papilla
(Fig. 35.4). Within the duodenal wall, surrounding the terminal portion of the ampulla of Vater,
is a smooth muscle sphincter complex (Sphincter of Oddi). This sphincter controls exocrine
secretions from the common bile duct and main
pancreatic duct. In about 14% of patients the
common bile duct and main pancreatic duct
enter the duodenum through separate orifices.
463
PANCREAS
Fig. 35.4. The pancreatic ducts.
The accessory pancreatic duct (duct of Santorini), when present, drains the anterosuperior
portion of the head. It enters the duodenum
through the minor papilla, which is often
located approximately 2 cm superior to the
major papilla (Fig. 35.4). The pancreatic duct
at its widest point – the entrance to the duodenum – measures 3.1–4.8 mm, within the body it
averages 2–3.5 mm and toward the tail it tapers
to a diameter of 0.9–2.4 mm [2]. The major
pancreatic arterial and venous structures are
located posterior to the main pancreatic duct.
Arterial Supply of the Pancreas
The blood supply to the pancreas originates
from the celiac trunk and the superior mesenteric artery. The pancreaticoduodenal arcades
provide most of the blood supply to the head
of the pancreas and the duodenum. The paired
superior anterior and posterior pancreaticoduodenal arteries arise from the gastroduodenal
artery which isa branch off the common hepatic
artery. These arteries descend and coalesce with
the inferior anterior and posterior pancreaticoduodenal branches from the superior mesenteric artery to form the pancreaticoduodenal
arcades (Fig. 35.3). Both the head of the
pancreas and the duodenum share a common
blood supply derived from these arcades. The
posterior superior pancreaticoduodenal artery
also supplies the distal common bile duct and
the ampulla of Vater. Occasionally, the inferior
pancreaticoduodenal artery arises from the first
jejunal branch of the superior mesenteric artery.
The uncinate process is supplied by smaller
vessels arising either from the inferior pancreaticoduodenal arteries or directly from the
superior mesenteric artery.
The splenic artery, as it courses along the
superior border of the pancreas, gives off multiple branches supplying the neck and body
(Fig. 35.3). The major branch from the splenic
artery is the dorsal pancreatic artery which may
in some cases arise directly from the celiac
(22%), superior mesenteric (14%), or common
hepatic artery (12%) [9]. The dorsal pancreatic
artery gives off a left and right branch. The right
branch usually anastomoses with the posterior
superior arcade. The left branch will form the
transverse pancreatic artery. This artery runs
along the posteroinferior border of the pancreas
and anastomoses with the more distal splenic
artery branches, the great pancreatic and caudal
pancreatic arteries. The great pancreatic artery
is the largest splenic artery branch and arises
464
ENDOCRINE SURGERY
from the splenic artery between the body and
the tail of the gland. The tail is supplied by
the caudal pancreatic arteries, which generally
arise from the splenic or left gastroepiploic
arteries.
There are several notable variations in hepatic artery origin. These variations are relevant to
pancreatic surgery, as they are often closely
related to the head of the pancreas and at risk
of injury during pancreaticoduodenectomy. In
most of the population, the hepatic artery
branches from the common hepatic artery,
which itself derives from the celiac trunk. However, a common hepatic artery may arise
directly from the superior mesenteric artery. It
sometimes passes through the head of the
pancreas and behind the portal vein, before
bifurcating into right and left hepatic artery
branches. Accidental ligation of this artery will
lead to hepatic ischemia. An aberrant right
hepatic artery arising from the superior mesenteric artery is also commonly found. This artery
may pass posterior to the head before entering
the porta hepatis posterior to the common bile
duct or portal vein. An anomalous left hepatic
artery may arise from the superior mesenteric
artery or the gastroduodenal artery [3].
Venous Supply
Lymphatic Drainage
The pancreas possesses an extensive network
of lymphatics. Within the lobules of the gland,
lymphatics are relatively sparse. However
lymphatics are substantial within the interand intralobular spaces and are associated
with blood vessels and connective tissue. These
interlobular lymphatics travel with blood vessels to the surface of the gland where they drain
to lymph nodes surrounding the pancreas. The
superior lymphatic vessels course along the
upper border of the pancreas closely associated
with the splenic vessels. They receive lymphatic
flow from the body and tail and empty into the
superior body and splenic lymph nodes. The
head of the pancreas is drained by lymphatics,
which empty into the anterior and posterior
pancreaticoduodenal lymph nodes. Also receiving lymph from the head and body are the
gastroduodenal, pyloric, and hepatic nodes.
Lymph may also flow directly from the head to
the juxta aortic and paraaortic lymph nodes.
The tail and the left side of the body empty
into the splenic nodes, which adjoin the hilum
of the spleen. The gastrosplenic nodes lying
within the gastrosplenic ligament receive lymphatic drainage from the tail and the left part
of the pancreatic body [10].
The pancreatic veins generally run parallel and
superficial to the arteries. The head is drained by
the pancreaticoduodenal venous arcade. The
posterior superior pancreaticoduodenal vein
often crosses the bile duct posteriorly to empty
into the portal vein at the superior margin of the
pancreas. The anterior superior pancreaticoduodenal vein drains into the superior mesenteric
vein via the gastrocolic trunk. Both the inferior
anterior and the posterior pancreaticoduodenal
veins drain into the superior mesenteric vein. At
times, they converge before joining the superior
mesenteric vein. The splenic vein runs along the
posterior superior border of the pancreas receiving tributaries from the tail, body, and neck. It
joins the superior mesenteric vein behind the
neck of the gland to form the portal vein. The
transverse pancreatic vein courses inferior to the
splenic vein and empties into the inferior mesenteric vein. The inferior mesenteric vein then
empties into either the splenic (60%) or the
superior mesenteric vein (40%) [9].
Innervation of the Pancreas
The pancreas has both sympathetic and
parasympathetic innervation, which regulate
pancreatic blood flow as well as endocrine and
exocrine function. The pancreas is also richly
innervated with pain fibers from the celiac
plexus and splanchnic trunks. Parasympathetic
innervation originates from the vagus nerve,
which transmits preganglionic input from the
brainstem. The vagal nerve fibers pass through
the celiac ganglion without synapsing; instead
they terminate at intrapancreatic ganglion
cells which then give off postganglionic fibers
to innervate the islet cells, acini, and ducts.
Signaling from the vagus is known to stimulate
release of insulin and other pancreatic hormones [11].
The sympathetic nerves originate from the
splanchnic trunks, which travel to the celiac
and superior mesenteric ganglia where they
synapse and send postganglionic fibers to
465
PANCREAS
innervate the pancreas. Postganglionic nerve
fibers innervate blood vessels as well as endocrine cells [12].
Physiology of the Pancreas
The pancreas plays a key role in glucose homeostasis as well as in the digestive process. These
functions can be separated into exocrine and
endocrine functions, each possessing unique
physiology. In this chapter we focus on the
endocrine physiology of the pancreas.
The endocrine pancreas is comprised of islets
of Langerhans, which are distributed throughout
the pancreas, and makes up approximately
1–2% of its mass. In a normal pancreas there
are about 1,000,000 islets of Langerhans. These
islets vary in size and may contain several thousand cells of different endocrine type. It was previously thought that human islets are much like
the rat islet, where beta cells are concentrated at
the core and alpha, delta, and PP cells are scattered throughout the mantle. However, more
recent studies on human islets have shown that
beta, alpha, and delta cells are generally aligned
alongbloodvesselsinnoparticularorder.Infact,
beta cells are often found in contact with other
nonbeta cells [13]. Beta cells, the insulin-producing endocrine cells of the pancreas, make up
60–80% of islet cells. The glucagon-producing
alpha cells make up 20–30% endocrine cells
and delta cells around 5–15%. Delta and PP are
scattered throughout the islet and secrete somatostatin and pancreatic peptide respectively. Pancreatic islets have an extensive capillary network
with at least one arteriole supplying each islet
[14]. Scanning electron microscopic studies of
rat islet cells indicate that arterial blood enters
the islet mantle at one pole and crosses the core
to the opposite pole where it then leaves the islet
[15]. Physiology studies have also suggested a
unidirectional flow of blood with delta cells
located downstream from beta cells [16]. A unidirectional flow of blood supports the hypothesis
that secretory products of beta cells exert a
paracrine effect on the downstream islet cells.
However, this requires further anatomic and
physiologic investigation.
Beta Cells
Beta cells are the insulin-producing cells of
the pancreas. Morphologically these cells are
polyhedral and contain large numbers of secretory granules. Their main peptide product is
insulin, a 56-amino acid molecule that is
arranged into an alpha and beta chain connected by disulfide bridges. Insulin is an anabolic hormone that stimulates the uptake and
storage of glucose and amino acids. It is first
produced as a propeptide (proinsulin), which is
stored within zymogen granules where it is
cleaved into C-peptide and insulin. When beta
cells are stimulated, both C-peptide and insulin
are released into the blood stream via exocytosis. The release of secretory granules is modulated by a number of factors including circulating levels of glucose and amino acids, signaling
from the autonomic nervous system, and the
incretin hormones glucose-dependent insulinotropic peptide (GIP), and glucagon-like peptide
1 (GLP-1) (Fig. 35.5).
Beta-cell physiology is quiet complex and has
been studied extensively. The main insulin
secretagogue is glucose; hyperglycemia induces
its secretion in a feedback mechanism, which
maintains circulating levels within a narrow
physiologic range. Glucose acts on the beta cell
through a specific glucotransporter (GLUT2)
[17]. The GLUT2 transporter is highly efficient
and quickly equilibrates intra- and extracellular
glucose levels. On entering the cell, glucose is
phosphorylated by glucokinase and enters the
glycolytic pathway to produce pyruvate. Pyruvate then enters the mitochondria where it is
further metabolized in the tricarboxylic acid
cycle (TCA) to form NADH and FADH2 [18].
These molecules carry the reducing power
required for the activation of the electron transport chain. The change in membrane potential
resulting from activation of the electron transport chain powers the oxidative phosphorylation of ADP to ATP. An enhanced ratio of ATP
to ADP within the cell then causes the closure of
ATP-sensitive K+ channels, which in turn depolarizes the plasma membrane and opens the
voltage-dependent L-type Ca
ing to an influx of Ca
increased cytoplasmic concentration of Ca
2+
2+
channels lead-
into the cell. This
2+
through its action on protein kinase C, protein
kinase A, and calmodulin, initiates exocytosis of
insulin containing secretory granules. Other
peptide hormones such as GLP-1 and GIP interact with receptors on the beta-cell membrane
to increase cAMP which also activates protein
kinase A. Amino acids interact with a
466
ENDOCRINE SURGERY
Fig. 35.5. Overview of intracellular pathways involved in insulin secretion. Glucose enters the cell through GLUT2 transporters. The
metabolism of glucose increases intracellular ATP which causes the closure of K
membrane depolarization and an influx of Ca
containing granules. Amino acids bind to the cell membrane receptor GPR40 which acts to directly increase intracellular Ca
stimulate granule secretion. Acetylcholine binds to M
diacylglycerol (DAG) and inositol triphosphate (IP
increases intracellular Ca2+which results in granule exocytosis. Glucose-dependent insulinotropic peptide (GIP) and glucagon-
IP
3
like peptide-1(GLP-1) bind to transmembrane receptors which stimulates the production of cyclic AMP (cAMP). cAMP then activates
protein kinase A (PKA) which results in granule exocytosis. Courtesy of Harma Turbendian, Weill Cornell Medical College.
transmembrane receptor GPR40 to increase
cytoplasmic Ca
2+
and thereby stimulate granule
exocytosis [18, 19]. Like glucose, the metabolism of amino acids promotes the synthesis of
ATP and thus increases the ATP/ADP ratio
within the cell.
2+
into the cytoplasm. Increased intracellular Ca2+stimulate the exocytosis of insulin-
muscarinic receptors causing the conversion of phosphatidylinositol (PIP2)to
3
). DAG causes insulin secretion by activation of protein activation kinase C (PKC).
3
connects islet amyloid deposition with betacell loss and progressive type II diabetes [21].
In humans, the degree of amyloid deposition
has been found to correlate with decreased
beta-cell mass as well as severity of type II diabetes [22].
-channels. Closure of K
ATP
-channels then leads to
ATP
2+
and
Beta cells also produce islet amyloid poly-
peptide (IAPP or Amylin), a 37-amino acid pep-
Alpha Cells
tide that is also stored in secretory granules and
co-released with insulin. The Amylin gene IAPP
is expressed specifically in the beta cells of the
pancreas [20]. The exact function of amylin is
unclear; however it is thought to act as an inhibitor of insulin secretion. Studies have shown
that in type II diabetes, amylin peptides aggregate to form amylin fibrils, which are thought to
be toxic to beta cells. In fact, amyloid deposits
are a characteristic pathologic finding in type II
diabetes, and a growing body of evidence
Alpha cells are columnar shaped islet cells that
contain a large number of secretory granules.
The primary secretory product is glucagon, a
29-amino acid peptide. Glucagon acts on the
liver during hypoglycemic states to stimulate
glycogenolysis and gluconeogenesis thus
increasing circulating glucose levels. It is
believed that like insulin, glucose acts as the
primary glucagon secretogogue; hyperglycemia
inhibits secretion while hypoglycemia promotes
467
PANCREAS
it. There is however an ongoing debate as to
whether alpha cells respond to fluctuations in
plasma glucose, possibly signaling through the
autonomic nervous system or through the
microcirculatory environment of the cell (paracrine effect) created by the secretory products of
the other islet cells [23]. It is likely that all these
act as stimuli for alpha-cell secretion of glucagon. Recent studies have shown clear relationships between alpha-cell microenvironment
and cell regulation. Specifically, the beta-cell
products insulin and zinc have been studied.
Studies of rat alpha cells have demonstrated
the presence of a cell membrane insulin receptor and have also shown that insulin transiently
inhibits electrical activity by hyperpolarizing
the cell membrane and consequently inhibiting
glucagon secretion [24, 25]. Zinc, which is
stored in beta cells along with insulin and
released in response to high levels of glucose,
is also believed to play a role in cell signaling. In
rats, zinc has been shown to reversibly inhibit
glucose-stimulated glucagon release from alpha
cells and also reversibly activate K
thereby reducing electrical activity and glucagon secretion [25]. Physiology studies on
human alpha cells have yet to substantiate
these findings. Glucagon secretion is also closely regulated by the autonomic nervous system. Decreased arterial glucose concentration
is detected predominantly in the ventromedial
hypothalamus. Evidence suggests that glucosesensing neurons in the ventromedial hypothalamus function through a mechanism similar
to that of the beta cell, where activation of
K
-channels causes the release of neurotrans-
ATP
mitters [23, 26]. This leads to increased sympathetic input to the alpha cells and increased
circulating epinephrine levels, both of which
result in glucagon secretion [23].
-channels
ATP
Delta Cells
Delta cells are small dendritic cells, which produce somatostatin, a 14-amino acid peptide,
initially produced as prosomatostatin. Prosomatostatin is a 92-amino acid peptide, which is
cleaved to yield somatostatin-14 and somatostatin-28. Variations in these two molecular
forms of somatostatin are found in different
tissue types [27]. Somatostatin-14 is the main
pancreatic delta-cell product and is a potent
inhibitor of both insulin and glucagon secretion. Somatostatin is released from delta
cells in response to hyperglycemia and amino
acids [28]. Autonomic input occurs via both
parasympathetic and sympathetic branches.
Parasympathetic activation will stimulate somatostatin secretion while sympathetic activation
is inhibitory.
PP Cells
PP cells (F cells) produce pancreatic polypeptide,
a 36-amino acid peptide which is secreted predominately by vagal stimulation [29]. Pancreatic
polypeptide inhibits secretion of pancreatic
enzymes, bile, and also suppresses insulin secretion. However, its main physiologic function
remains unknown.
Autonomic Innervation
of Islet Cells
Parasympathetic Innervation
The islets of Langerhans are well innervated by
the autonomic nervous system. The parasympathetic branch of the autonomic nervous system
is an important regulator of physiologic islet
hormone secretion [30]. Parasympathetic fibers
originate in neurons with ganglia located within
the pancreatic parenchyma. The intrapancreatic
ganglia receive neural input from the brainstem
via the vagus nerve and also receive input from
the enteric nervous system. Activation of the
vagus stimulates insulin secretion mainly during the cephalic phase of meal-induced insulin
secretion. However, recent studies suggest a
larger role for vagally induced postprandial
insulin secretion [31]. There are two major
mechanisms by which vagal stimulation results
in the secretion of insulin from beta cells. First,
vagal activity leads to the release of acetylcholine, which binds to muscarinic receptors
located on the beta-cell membrane (Fig. 35.5).
These muscarinic receptors are coupled with
sodium channels within the membrane. Activation of sodium channels leads to an increase in
membrane potential, intracellular Ca
and subsequent secretion of insulin. The vagus
can also act to stimulate the release of GLP-1
from the intestinal L cells. GLP-1 binds to
2+
release,
468
ENDOCRINE SURGERY
specific receptors on the beta-cell membrane,
which induces adenyl cyclase and the conversion of ADP to cAMP. Cyclic AMP then activates
protein kinase A, which causes an increase in
intracellular calcium and the release of insulin.
Second, the vagus may act through an acetocholine-mediated increase in phospholipases A2, C,
and D which hydrolyzes phosphatidylinositol to
diacylglycerol (DAG) and inositol triphosphate.
DAG then stimulates protein kinase C which
phosphorylates myristoylated alanin-rich protein kinase C and exocytosis of granules [32].
Sympathetic Innervation
The beta cells of the pancreas receive sympathetic input from the hypothalamus via postganglionic fibers from the thoracic and lumbar
sympathetic chain. Sympathetic activation
causes the release of norepinephrine and epinephrine which activate
and 2cadrenore-
2a
ceptors. These adrenoreceptors act to inhibit
adenyl cyclase and lower levels of cAMP which
keeps the potassium channels open, the resting
membrane potential negative, and thereby
reduces insulin secretion [33]. In alpha cells
epinephrine stimulates adenyl cyclase activity
which increases intracellular Ca
2+
and results
in glucagon secretion [32]. Sympathetic activation has also been shown to inhibit somatostatin
secretion [34].
Neuropeptides Involved in
Autonomic Regulation of Islet Cells
The neuropeptides vasoactive intestinal polypeptide (VIP) and pituitary adenylate cyclaseactivating polypeptide (PACAP) modulate
parasympathetic input to the islet cells. VIP is
a 28-amino acid neuropeptide that is released
from parasympathetic nerve terminals within
the islets and acts to stimulate beta-cell insulin
secretion as well as alpha-cell glucagon release
[30]. PACAP is a 38-amino acid neuropeptide
that has also been shown to stimulate insulin
and glucagon secretion [35]. Both VIP and
PACAP bind to G-protein-coupled membrane
receptors which mediate an increase in cAMP
and intracellular Ca
exocytosis of insulin-containing vesicles
[33, 36].
2+
levels, thus facilitating
The neuropeptide galanin is a 29-amino acid
neuropeptide, which is widely distributed
throughout the central and peripheral nervous
system, the gastrointestinal tract, and the pancreas. It is expressed in the sympathetic nerve
terminals surrounding the pancreatic islet cells.
Although the underlying molecular mechanisms remain unclear, galanin is a potent inhibitor of insulin secretion. There is experimental
evidence that galanin acts directly on the beta
cell to inhibit adenyl cyclase and decrease cAMP
[37]. It has also been shown to inhibit somatostatin secretion and stimulate glucagon
secretion.
Neuropeptide Y (NPY) is a 36-amino acid
peptide that shares structural homology with
pancreatic polypeptide and peptide YY. It is
produced in the central and peripheral nervous
system. Release of NPY has been demonstrated
at sympathetic nerve terminals of islet cells. It is
believed that NPY plays a role in the autonomic
regulation of insulin secretion. Islet physiology
studies have demonstrated an inhibitory effect
on insulin release in several species [30].
Further human islet studies are required to substantiate these findings.
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