Transcript Managing people in sport organisations: A strategic human resource

Chapter 6
Companion site for Basic Medical Endocrinology, 4th Edition
Author: Dr. Goodman
FIGURE 6.1
The gastrointestinal tract. A. The stomach and its functional segments. The lining of the body or
corpus contains the acid secreting oxyntic mucosa. The antrum and pylorus control access to the
initial portion of the intestine, the duodenum. B. The accessory digestive organs, the liver and
pancreas. Bile contains excretory products and the sterols and phospholipids that emulsify ingested
fats and facilitate their digestion and absorption. C. The intestines. The duodenum is about 30 cm
long and leads into the jejunum (about 2.5 meters long), which in turn leads into the ileum (about
3.8 meters long). The large intestine, the colon, is comprised of the ascending, transverse, and
descending portions.
Companion site for Basic Medical Endocrinology, 4th Edition. by Dr. Goodman
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FIGURE 6.2
Gastric glands. Hormone secreting cells in the epithelial lining of the stomach and intestinal tract
are present in deep invaginations of the mucosal surface scattered among cells of various
functions. A. Schematic representation of an oxyntic pit. Note that the acid-producing parietal cells,
the enzyme-producing chief cells, and the mucus-producing cells and the differentiating cells that
renew the mucosal surface are all “open” to the lumen and come in direct contact with the luminal
contents. The ECL (enterochromaffin-like) cells, the somatostatin-secreting D cells, and the ghrelin
producing cells are “closed” and have no direct contact with luminal contents. B. Schematic
representation of the antral pit. Note that parietal cells are absent, and that the somatostatin
producing D cells, the gastrin-producing G cells, and the enterochromaffin cells are “open” and
come in contact with the luminal contents. A similar arrangement of cells is seen in the crypts of the
mucosae of the small and large intestines.
Companion site for Basic Medical Endocrinology, 4th Edition. by Dr. Goodman
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FIGURE 6.3
Schematic representation of the enteric nervous system and its connections to sympathetic and
parasympathetic neurons. Interneurons and cell bodies of sensory and motor neurons of the enteric
nervous system are found in the submucosal plexus and in the myenteric plexus, which lies
between the layers of longitudinal and circular smooth muscle. Signals are transmitted both laterally
through the layers of the wall and along the length of the GI tract. Enteric neurons communicate
with sensory and motor vagal fibers and with sympathetic postganglionic fibers, which also directly
innervate blood vessels, intestinal smooth muscle and mucosal secretory cells. (Redrawn from
Johnson, L.R. (2003) Essential Medical Physiology, 3rd ed., 469. Elsevier, Academic Press, San
Diego.)
Companion site for Basic Medical Endocrinology, 4th Edition. by Dr. Goodman
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FIGURE 6.4
Vago-vagal reflexes. Sensory signals arising directly from vagal chemo- or mechanoreceptors or
transmitted to vagal afferents from enteric neurons pass up the vagus nerve trunks to neurons in
the nucleus of the solitary tract, which communicate with efferent neurons in the dorsal motor
nucleus and the nucleus ambiguous (vagal integrating centers). Efferent signals travel down the
vagal trunks to activate or inhibit secretion or contraction directly or indirectly by way of the enteric
nervous system.
Companion site for Basic Medical Endocrinology, 4th Edition. by Dr. Goodman
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FIGURE 6.5
Progastrin, procholecystokinin (CCK), and their posttranslational processing. Amino acids are
represented in the single-letter amino acid code. Identical amino acid residues in corresponding
positions in both hormones are shown in red, and are found largely in the carboxyl terminus.
Posttranslational processing removes the 8 amino acids from the carboxyl terminal of progastrin
and 11 amino acids from proCCK. The C-terminal glycine is then cleaved, leaving behind its amino
group as an amide on the new C-terminal phenylalanine. Amidation is critical for bioactivity of both
hormones. Subsequent cleavage by hormone convertases (blue arrows) produces the most
prevalent forms of gastrin and CCK. A = alanine, C = cysteine, D = aspartic acid, E = glutamic acid,
F = phenylalanine, G = glycine, H = histidine, I = isoleucine, K = lysine, L = leucine, M = methionine,
N = asparagine, P = proline, Q = glutamine, R = arginine, S = serine, T = threonine, V = valine, W =
tryptophan, Y = tyrosine.
Companion site for Basic Medical Endocrinology, 4th Edition. by Dr. Goodman
Copyright © 2009 by Academic Press. All rights reserved.
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FIGURE 6.6
Stimulation of gastric acid secretion. Histamine secreted by enterochromaffin-like (ECL) cells is the
principal stimulus for acid (H+) secretion by parietal cells, which receive direct cholinergic (Ach)
neural input and endocrine input from gastrin. The vagus provides stimulatory input to ECL cells
with the postganglionic neurotransmitter PACAP (pituitary adenyl cyclase activating peptide), and to
the gastrin producing G cells with the postganglionic neurotransmitter GRP (gastrin releasing
peptide). G cells also secrete gastrin in response to direct stimulation by peptides and amino acids
in the antral lumen.
Companion site for Basic Medical Endocrinology, 4th Edition. by Dr. Goodman
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FIGURE 6.7
Cellular actions of gastrin, acetylcholine, and histamine on the parietal cell. Convergence of
signaling pathways results in synergistic stimulation of hydrochloride acid.
Companion site for Basic Medical Endocrinology, 4th Edition. by Dr. Goodman
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FIGURE 6.8
Actions of gastrin and PACAP in ECL cells. Both gastrin and PACAP stimulate G-protein-coupled
receptors to activate the IP3 (inositol trisphosphate)/DAG (diacylglycerol phosphate) pathway and
increase intracellular Ca2+. IP3 stimulates release of Ca2+ from the endoplasmic reticulum (ER),
and DAG-dependent activation of protein kinase C (PKC) results in phosphorylation and activation
of membrane calcium channels. Increased Ca2+ triggers release of preformed histamine from
storage granules and induces expression of histidine decarboxylase (HDC), the enzyme that
catalyzes histamine formation, and expression of at least two proteins, chromagranin (CGA) and
vesicular monoamine transporter type 2 (VMAT-2).
Companion site for Basic Medical Endocrinology, 4th Edition. by Dr. Goodman
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FIGURE 6.9
Direct and indirect feedback regulation of gastrin secretion. Gastrin secretion is positively regulated
by luminal nutrients and gastrin releasing peptide (GRP), and is negatively regulated by
somatostatin (SST). Gastrin reaches D cells in both the antral and oxyntic mucosae by paracrine or
endocrine pathways and stimulates them to secrete SST. Increased luminal H+ concentrations
stimulate antral and duodenal D cells to secrete SST. Increased H+ concentrations in the
duodenum and luminal nutrients in the intestine increase secretion of enteric hormones, which
stimulate D cells in the gastric and duodenal mucosae to secrete SST. Increased luminal H+
concentrations are sensed by neuronal chemoreceptors and initiate vago–vagal reflexes, which
result in decreased release of GRP and decreased cholinergic inhibition of D cells.
Companion site for Basic Medical Endocrinology, 4th Edition. by Dr. Goodman
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FIGURE 6.10
Effects of somatostatin (SST) and control of its secretion in the gastric mucosa. D cells in the
oxyntic mucosa have no access to the luminal contents and are stimulated to secrete SST by
hormones secreted by endocrine cells downstream in the GI tract, and inhibited by vagal
cholinergic nerves. SST secreted by these cells acts mainly as a paracrine factor. D cells in the
antral mucosa are stimulated by increases in H+ concentrations and circulating enteric hormones,
and are inhibited by vagal cholinergic neurons.
Companion site for Basic Medical Endocrinology, 4th Edition. by Dr. Goodman
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FIGURE 6.11
Effects of ingestion of a standardized liquid meal (arrow) on plasma concentrations of
cholecystokinin, gall bladder contraction, and pancreatic chymotrypsin secretion in normal subjects.
(Redrawn from data of Liddle, R.A., Goldfine, I.D., Rosen, M.S., Taplitz, R.A., and Williams, J.A.
(1985) Cholecystokinin activity in human plasma. Molecular forms, responses to feeding and
relationship to gall bladder contraction. J. Clin. Invest. 75: 1144–1152; and Owyang, C., Louie, D.S.,
and Tatum, D. (1986) Feedback regulation of pancreatic enzyme secretion. Suppression of
cholecyctokinin release by trypsin. J. Clin. Invest. 77: 2042–2047.)
Companion site for Basic Medical Endocrinology, 4th Edition. by Dr. Goodman
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FIGURE 6.12
Actions of CCK on pancreatic secretion and bile flow. Major direct actions are indicated by solid
blue arrows. Effects of questionable physiological significance are indicated by the dotted blue
arrows.
Companion site for Basic Medical Endocrinology, 4th Edition. by Dr. Goodman
Copyright © 2009 by Academic Press. All rights reserved.
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FIGURE 6.13
Regulation of CCK secretion. Red arrows indicate inhibitory influences. LCRF = Luminal
Cholecystokinin Releasing Factors.
Companion site for Basic Medical Endocrinology, 4th Edition. by Dr. Goodman
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FIGURE 6.14
The secretin/glucagon family of peptides. Amino acids are represented by the single letter amino
acid code. Residues colored red are identical with those in corresponding positions in secretin.
Residues colored cyan or green are identical with those in corresponding positions in at least three
family members. Beyond residue 30, in the C terminal region, sequence divergence is almost
complete. In most of these peptides the carboxyl terminal amino acid is amidated. A = alanine, C =
cysteine, D = aspartic acid, E = glutamic acid, F = phenylalanine, G = glycine, H = histidine, I =
isoleucine, K = lysine, L = leucine, M = methionine, N = asparagine, P = proline, Q = glutamine, R =
arginine, S = serine, T = threonine, V = valine, W = tryptophan, Y = tyrosine.
Companion site for Basic Medical Endocrinology, 4th Edition. by Dr. Goodman
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FIGURE 6.15
Actions of secretin on bicarbonate secretion by pancreatic and bile duct epithelial cells. Stars
indicate processes that are stimulated by secretin through increased cyclic AMP formation and
protein kinase A-dependent phosphorylation (see text for explanation).
Companion site for Basic Medical Endocrinology, 4th Edition. by Dr. Goodman
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FIGURE 6.16
Synergistic effects of secretin and CCK on bicarbonate secretion. Secretin alone, CCK alone or
secretin and CCK in combination were infused intravenously in six normal human subjects.
Bicarbonate output was assessed in samples of duodenal fluids collected through a naso-gastric
tube. (Redrawn from data of Refeld, J.F. (2004) Best Practice and Research in Clinical
Endocrinology and Metabolism 18: 569–586.)
Companion site for Basic Medical Endocrinology, 4th Edition. by Dr. Goodman
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FIGURE 6.17
Schematic representation of the actions of secretin and feedback regulation of its secretion. Solid
arrows indicate stimulation; dashed arrows indicate inhibition. LSRF = luminal secretin releasing
factors.
Companion site for Basic Medical Endocrinology, 4th Edition. by Dr. Goodman
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FIGURE 6.18
The incretin effect. Infusion of a solution of 500 mg.of glucose intrajejunally produces a smaller
increase in plasma glucose concentration than infusion of the same amount of glucose
intravenously (upper panel), but the jejunal infusion elicits a much greater increase (55-fold vs. 12fold) in insulin secretion. (Reproduced from McIntyre, N., Holdsworth, C.D., and Turner, D.S. (1965)
Intestinal factors n the control of insulin secretion. J. Clin. Endocrinol. Metab. 25: 1317.)
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FIGURE 6.19
Effects of different dietary nutrients in secretion of incretin hormones. Eight healthy volunteers were
fed 375-calorie meals consisting of only glucose, protein, or fat. Venous blood was sampled at the
indicated times. A. Glucose and fat promptly increased plasma concentrations of GIP (glucosedependent insulinotropic peptide), but proteins had no effect on GIP secretion. B. Glucose and
protein promptly increased plasma levels of GLP-1 (glucagon-like peptide 1), but the response to
the fatty meal was delayed. Note the difference in the scales for plasma concentrations of GIP and
GLP in panels A and B, and note also that peak plasma concentrations of both hormones were
achieved in 30 minutes after the glucose meal. C. Plasma concentrations of insulin were increased
only after the glucose meal, which also increased plasma insulin concentrations (Panel D). Plasma
glucose and insulin concentrations were unchanged after ingesting protein or fat, despite increased
secretion of GIP and GLP-1, illustrating the glucose dependence of the incretin effect. (Redrawn
from the data of Elliot, R.M., Morgan, L.M., Tredger, L.A., Deacon, S., Wright, J., Marks, V. (1993)
Glucagon-like peptide-1 (7-36) amide and glucose-dependent insulinotropic polypeptide secretion
in response to nutrient ingestion in man: Acute post-prandial and 24-h secretion patterns. J.
Endocrinol. 138: 162.)
Companion site for Basic Medical Endocrinology, 4th Edition. by Dr. Goodman
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FIGURE 6.20
Post-translational processing of proglucagon. Black arrows indicate dibasic sites of cleavage by
hormone convertases. The green arrow points to a monobasic cleavage site. The cross-hatched
area represents the hexapeptide N-terminal extension found in the immature glucagon-like peptide
1 (GLP-1). The final products of pancreatic alpha cells and intestinal L cells are determined by the
presence of different convertases in the two cell types. GRPP = Glicentin-related pancreatic
peptide; GLP-2 = glucagon-like peptide-2.
Companion site for Basic Medical Endocrinology, 4th Edition. by Dr. Goodman
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FIGURE 6.21
Effects of glucagon-like peptide-1 (GLP-1) infusion on gastric emptying and acid secretion following
ingestion of a standardized liquid meal in nine healthy male volunteers. Subjects were given a
constant infusion of either saline or 1.2 pmol of GLP-1/kg/minute beginning 30 minutes before
eating and continuing through the subsequent 4 hours (green bar). The arrow indicates the time of
meal ingestion. (Redrawn from the data of Nauck, M.A., Niedereichholz, U., Ettler, R., Holst, J.J.,
Orskov, C., Ritzel, R., Schmiegel, W.H. (1997) Glucagon-like peptide 1 inhibition of gastric
emptying outweighs its insulinotropic effects in healthy humans. Am. J. Physiol. Endocrinol. Metab.
273: E981–E988.)
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FIGURE 6.22
The ileal brake. (GLP-1 = glucagon-like peptide-1)
Companion site for Basic Medical Endocrinology, 4th Edition. by Dr. Goodman
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FIGURE 6.23
Amino acid sequences of the PPY (PPfold) family of peptides using the single letter amino acid
code. Residues shown in red are identical in corresponding positions in all three peptides.
Residues shown in cyan or green are identical with those in corresponding positions in two family
members. A = alanine, C = cysteine, D = aspartic acid, E = glutamic acid, F = phenylalanine, G =
glycine, H = histidine, I = isoleucine, K = lysine, L = leucine, M = methionine, N = asparagine, P =
proline, Q = glutamine, R = arginine, S = serine, T = threonine, V = valine, W = tryptophan, Y =
tyrosine.
Companion site for Basic Medical Endocrinology, 4th Edition. by Dr. Goodman
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FIGURE 6.24
The effects of isocaloric test meals of carbohydrate, protein, and fat on plasma concentrations of
neurotensin in healthy young adult subjects. (Redrawn from Rosell, S. and Rökaeus, Ä. (1979) The
effect of ingestion of amino acids, glucose and fat on circulating neurotensin-like immunoreactivity
(NTLI) in man. Acta. Physiol. Scand. 107: 263–267.)
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FIGURE 6.25
The motilin ghrelin family. A. Post-translational processing of prepromotilin and preproghrelin.
Cleavage of proghrelin releases ghrelin from the N terminus and a second peptide called obestatin,
which may have biological activity. B. Amino acid sequences of motilin and ghrelin represented with
the single amino acid code. Insertion of a gap between residues 15 and 16 in motilin optimizes the
correspondence to the sequence of ghrelin and probably represents the loss of a codon. The
octanoate held in ester linkage with the serine at position 3 of ghrelin is essential for activity.
Companion site for Basic Medical Endocrinology, 4th Edition. by Dr. Goodman
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FIGURE 6.26
Effects of motilin on gastric muscle tone. An intragastric balloon was placed in the stomachs of
normal fasted volunteers and filled with air. Changes in gastric muscle tone were detected as
changes in balloon volume: Increased muscle tone decreases balloon volume. Infusion of atropine,
which blocks acetylcholine receptors, resulted in expansion of the balloon, indicating a decrease in
tone. Infusion of motilin alone (not shown) or during the continued infusion of atropine increased
gastric tone as indicated by decreased volume of the balloon. This effect of motilin is not mediated
by parasympathetic stimulation of gastric muscle. (Redrawn from the data of Cuomo, R., Vandaele,
P., Coulie, B., Peeters, T., Depoortere, I., Janssens, J., and Tack, J. (2006) Influence of motilin on
gastric fundus tone and on meal-induced satiety in man: Role of cholinergic pathways. Am. J.
Gastroenterol. 101: 804–811.)
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FIGURE 6.27
Average plasma ghrelin concentrations during a 24-h period in 10 human subjects consuming
breakfast (B), lunch (L), and dinner (D) at the times indicated (0800, 1200, and 1730, respectively).
(From Cummings, D.E., Purnell, J.Q., Frayo, R.S., Schmidova, K., Wisse, B.E., and Weigle, D.S.
(2001) A preprandial rise in plasma ghrelin levels suggests a role in meal initiation in humans.
Diabetes 50: 1714–1719.)
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