Buona visione! Laini Flavia Vittoria

1. Regulation of Carbohydrate Metabolism
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VEDI ANCHE
POWER POINT DA PAGINE WEB

2. IL PANCREAS
inglese italiano
 Gland with both exocrine and
endocrine functions
 15-25 cm long
 60-100 g
 Location: retro-peritoneum, 2nd
lumbar vertebral level
 Extends in an oblique, transverse
position
 Parts of pancreas: head, neck,
body and tail
 È una ghiandola esocrina con e
funzioni endocrine
 Lungo 15-25 cm
 60-100 g
 Località: retro-peritoneale,
livello vertebrale lombare 2 °
 Estensione obliqua, posizione
trasversale
 Le parti del pancreas: testa,
collo, corpo e coda

3. Pancreas

4. FUNZIONI DEL PANCREAS
 Il pancreas è una ghiandola dalla forma allungata, situata nella parte
superiore della cavità addominale, tra il duodeno* e la milza*.
E' lunga circa 15 centimetri e si distinguono una testa, un corpo e una
coda.
Ha una duplice funzione:
- digestiva, poichè secerne due enzimi (l'amilasi e la lipasi)
necessari per la digestione degli amidi e dei grassi. Produce, infatti,
un secreto (il "succo pancreatico"), ricco di tali enzimi, che si riversa
nel duodeno attraverso il dotto di Wirsung e il dotto del Santorini;

- metabolica, in quanto attraverso la produzione di due ormoni
(l'insulina e il glucagone) regola il metabolismo degli zuccheri.

5. LIPASI: ESITO ANALISI PAVIA
DEL 29.10.2013

6. LE LIPASI
 Le lipasi sono enzimi coinvolti nel metabolismo dei lipidi, quelle
pancreatiche sono rilasciate nell’intestino per aiutare a digerire cibi
grassi; affinchè l’attività biochimica sia completa e per la massima
specificità sono necessari i sali biliari e un cofattore detto colipasi.
 Il pancreas è la fonte principali della lipasi circolante nel sangue,
presenti in quantità molto ridotte. Sia l’enzima sia la colipasi sono
sintetizzati dalle cellule acinari del pancreas che li secerne in
quantità grossomodo equivalenti.
 Quando le cellule del pancreas sono danneggiate, come nel caso
della pancreatite, o quando il dotto pancreatico è ostruito (ad
esempio da un calcolo o, in rari casi, da un tumore) aumenta la
concentrazione di enzima nel sangue.

8. ANNO 2009 GLUCOSIO 58 Mg/Dl ?????
L’INSULINA ALTA PROVOCA
IPOGLICEMIA

9. INSULINA E GH STIMOLANO LA
SINTESI PROTEICA!!!!!!
L'insulina ricopre un ruolo sulla sintesi
proteica in sinergia con gli ormoni GH
(o somatotropina), IGF-1 (o
somatomedina c) e il testosterone[2]
. In
seguito all'introduzione di proteine, gli
amminoacidi che ne derivano sono in
parte utilizzati per la sintesi proteica e
in generale l'accrescimento[3]
. Molti
degli amminoacidi possono stimolare
l'insulina, ma il loro potere
insulinogenico varia in base al tipo, ai
livelli di glucosio, e alla mescolanza con
esso (vedere amminoacidi
insulinogenici). Amminoacidi misti e un
pasto puramente proteico causano la
produzione di insulina, ma meno
rispetto ad un pasto puramente
glucidico. La secrezione di tale ormone
in seguito a un pasto proteico
promuove l'uptake e lo stivaggio di
amminoacidi sotto forma di proteine
muscolari e contrasta la proteolisi (il
catabolismo proteico), un processo che
promuove l'utilizzo di amminoacidi a
scopo energetico per gluconeogenesi,
principalmente durante il digiuno[4]
.
 L'insulina è un ormone peptidico dalle
proprietà anaboliche, prodotto dallecellule beta
delle isole di Langerhans all'interno del pancreas; è
formata da due catene unite da due ponti solfuro:
catena A di 21 aminoacidi e catena B di
30 aminoacidi. La sua funzione più nota è quella di
regolatore dei livelli diglucosio ematico riducendo la
glicemia mediante l'attivazione di diversi
processi metabolici e cellulari. Ha inoltre un
essenziale ruolo nellaproteosintesi (sintesi proteica)
assieme ad altri ormoni che sinergicamente
partecipano a tale processo, tra cui l'asse GH/IGF-1,
e il testosterone. L'insulina è il principale ormone
responsabile del fenomeno di ingrassamento
(lipogenesi), cioè lo stoccaggio di lipidi all'interno
del tessuto adiposo.

10. ORMONE GH
ANALISI ORMONALI GH

11. ANALISI ORMONALI GH E IGF1
GH ALTO 3,3 ng/ml contro
range 0,4
IGF 1 NELLA NORMA!

12. CARICO GLUCOSIO :OGTT (CURVA)

15. ORMONE LH

16. Utero deviato a sinistra??????
Probabilmente abbiamo un
problema ai genitali!
SI SPIEGA IL VALORE ALTO DI LH

17. VEDI MIA SLIDE
http://www.slideshare.net/F
LAVIAVITTORIA/patologie-
poliendocrine-amiloidosi-
da-laini-flavia-vittoria

19. Head of Pancreas
 Includes uncinate process
 Flattened structure, 2 – 3 cm thick
 Attached to the 2nd
and 3rd
portions of
duodenum on the right
 Emerges into neck on the left
 Border b/w head and neck is determined by
GDA insertion
 SPDA and IPDA anastamose between the
duodenum and the right lateral border

20. Traduzione slide precedente
 Include processo uncinato
 Struttura appiattita, 2 - 3 cm di spessore
 Attaccato alla parte 2 e 3 del duodeno sulla
destra
 Emerge nel collo a sinistra
 Bordo b/w della testa e del collo è
determinato da inserimento GDA
 SPDA e IPDA anastomosi dentro il duodeno
e il bordo laterale destro

21. Neck of Pancreas
 2.5 cm in length
 Straddles SMV and PV
 Antero-superior surface supports the pylorus
 Superior mesenteric vessels emerge from the inferior
border
 Posteriorly, SMV and splenic vein confluence to form
portal vein
 Posteriorly, mostly no branches to pancreas

22. Traduzione slide precedente
 2,5 cm di lunghezza
 Straddle SMV e PV
 Zona antero-superiore supporta il piloro
 Vasi mesenterici Superior emergono dal
confine inferiore
 Posteriormente, SMV e confluenza vena
splenica per formare vena porta
 Posteriormente, per lo più senza filiali al
pancreas

23. Body of Pancreas
 Elongated, long structure
 Anterior surface, separated from stomach by
lesser sac
 Posterior surface, related to aorta, lt. adrenal
gland, lt. renal vessels and upper 1/3rd
of lt.
kidney
 Splenic vein runs embedded in the post.
Surface
 Inferior surface is covered by transverse
mesocolon

24. Traduzione slide precedente
 Allungata, lungo la struttura
 Superficie anteriore separato da stomaco
minore sac
 Posteriore relativi alla aorta di superficie, lt.
ghiandola surrenale, lt. vasi renali e superiore
1/3 ° di lt. rene
 Corre vena splenica incorporati nel post. zona
 Superficie inferiore è coperta da mesocolon

25. Tail of Pancreas
 Narrow, short segment
 Lies at the level of the 12th
thoracic vertebra
 Ends within the splenic hilum
 Lies in the splenophrenic ligament
 Anteriorly, related to splenic flexure of colon
 May be injured during splenectomy (fistula)

26. Traduzione slide precedente
 Stretto, breve segmento
 Si trova a livello della 12°vertebra toracica
 Finisce nella milza - ilo
 Si trova nel legamento splenico
 Anteriormente, vicino alla flessura splenica
del colon
 Può essere feriti durante splenectomia
(fistola)

27. Pancreatic Duct
 Main duct (Wirsung) runs the entire length of
pancreas
 Joins CBD at the ampulla ofVater
 2 – 4 mm in diameter, 20 secondary branches
 Ductal pressure is 15 – 30 mm Hg (vs. 7 – 17 in
CBD) thus preventing damage to panc. duct
 Lesser duct (Santorini) drains superior portion of
head and empties separately into 2nd
portion of
duodenum

28. Arterial Supply of Pancreas
 Variety of major arterial sources (celiac, SMA and
splenic)
 Celiac  Common Hepatic Artery 
Gastroduodenal Artery  Superior
pancreaticoduodenal artery which divides into
anterior and posterior branches
 SMA  Inferior pancreaticoduodenal artery
which divides into anterior and posterior
branches

29. Arterial Supply of Pancreas
 Anterior collateral arcade between
anterosuperior and anteroinferior PDA
 Posterior collateral arcade between
posterosuperior and posteroinferior PDA
 Body and tail supplied by splenic artery by
about 10 branches
 Three biggest branches are
 Dorsal pancreatic artery
 Pancreatica Magna (midportion of body)
 Caudal pancreatic artery (tail)

30. Pancreatic Arterial Supply

31. Venous Drainage of Pancreas
 Follows arterial supply
 Anterior and posterior arcades drain head and
the body
 Splenic vein drains the body and tail
 Major drainage areas are
 Suprapancreatic PV
 Retropancreatic PV
 Splenic vein
 Infrapancreatic SMV
 Ultimately, into portal vein

32. Venous Drainage of the Pancreas

33. Lymphatic Drainage
 Rich periacinar network that drain into 5
nodal groups
 Superior nodes
 Anterior nodes
 Inferior nodes
 Posterior PD nodes
 Splenic nodes

34. Innervation of Pancreas
 Sympathetic fibers from the splanchnic nerves
 Parasympathetic fibers from the vagus
 Both give rise to intrapancreatic periacinar
plexuses
 Parasympathetic fibers stimulate both exocrine
and endocrine secretion
 Sympathetic fibers have a predominantly
inhibitory effect

35. Innervation of Pancreas
 Peptidergic neurons that secrete amines and
peptides (somatostatin, vasoactive intestinal
peptide, calcitonin gene-related peptide, and
galanin
 Rich afferent sensory fiber network
 Ganglionectomy or celiac ganglion blockade
interrupt these somatic fibers (pancreatic
pain)

36. Pancreatic Hormones, Insulin and
Glucagon, Regulate Metabolism

37. Production of Pancreatic Hormones
by Three Cell Types
Alpha cells produce glucagon.
Beta cells produce insulin.
Delta cells produce somatostatin.

38. Islet of Langerhans Cross-section
 Three cell types are present,
A (glucagon secretion), B
(Insulin secretion) and D
(Somatostatin secretion)
 A and D cells are located
around the perimeter while B
cells are located in the
interior
 Venous return containing
insulin flows by the A cells on
its way out of the islets

39. Pancreatic Hormones, Insulin and
Glucagon, Regulate Metabolism
Figure 22-8: Metabolism is controlled by insulin and glucagon

40. Structure of Insulin
 Insulin is a polypeptide hormone, composed of
two chains (A and B)
 BOTH chains are derived from proinsulin, a
prohormone.
 The two chains are joined by disulfide bonds.

41. Roles of Insulin
Acts on tissues (especially liver, skeletal
muscle, adipose) to increase uptake of glucose
and amino acids.
- without insulin, most tissues do not take in
glucose and amino acids well (except brain).
Increases glycogen production (glucose
storage) in the liver and muscle.
Stimulates lipid synthesis from free fatty acids
and triglycerides in adipose tissue.
Also stimulates potassium uptake by cells (role
in potassium homeostasis).

42. The Insulin Receptor
 The insulin receptor is composed of two subunits,
and has intrinsic tyrosine kinase activity.
 Activation of the receptor results in a cascade of
phosphorylation events:
phosphorylation of
insulin responsive
substrates (IRS) RAS
RAF-1
MAP-K
MAP-KK Final
actions

43. Specific Targets of Insulin
Action: Carbohydrates
Activation of glycogen synthetase. Converts
glucose to glycogen.
Inhibition of phosphoenolpyruvate
carboxykinase. Inhibits gluconeogenesis.
Increased activity of glucose transporters.
Moves glucose into cells.

44. Specific Targets of Insulin
Action: Lipids
Activation of acetyl CoA carboxylase. Stimulates
production of free fatty acids from acetyl CoA.
Activation of lipoprotein lipase (increases
breakdown of triacylglycerol in the circulation).
Fatty acids are then taken up by adipocytes, and
triacylglycerol is made and stored in the cell.
lipoprotein
lipase

45. Regulation of Insulin Release
 Major stimulus: increased blood glucose levels
- after a meal, blood glucose increases
- in response to increased glucose, insulin is
released
- insulin causes uptake of glucose into tissues, so
blood glucose levels decrease.
- insulin levels decline as blood glucose declines

46. Insulin Action on Cells:
Dominates in Fed State Metabolism
 ↑ glucose uptake in most cells
(not active muscle)
 ↑ glucose use and storage
 ↑ protein synthesis
 ↑ fat synthesis

47. Insulin Action on Cells:
Dominates in Fed State Metabolism

48. Insulin: Summary and Control
Reflex Loop

49. Other Factors Regulating
Insulin Release
 Amino acids stimulate insulin release (increased
uptake into cells, increased protein synthesis).
 Keto acids stimulate insulin release (increased
glucose uptake to prevent lipid and protein
utilization).
 Insulin release is inhibited by stress-induced increase
in adrenal epinephrine
- epinephrine binds to alpha adrenergic receptors on
beta cells
- maintains blood glucose levels
 Glucagon stimulates insulin secretion (glucagon has
opposite actions).

50. Structure and Actions of
Glucagon
Peptide hormone, 29 amino acids
Acts on the liver to cause breakdown of
glycogen (glycogenolysis), releasing glucose
into the bloodstream.
Inhibits glycolysis
Increases production of glucose from amino
acids (gluconeogenesis).
Also increases lipolysis, to free fatty acids for
metabolism.
Result: maintenance of blood glucose levels
during fasting.

51. Mechanism of Action of
Glucagon
 Main target tissues: liver, muscle, and adipose
tissue
 Binds to a Gs-coupled receptor, resulting in
increased cyclic AMP and increased PKA activity.
 Also activates IP3 pathway (increasing Ca++
)

52. Glucagon Action on Cells:
Dominates in Fasting State
Metabolism
 Glucagon prevents hypoglycemia by ↑ cell production
of glucose
 Liver is primary target to maintain blood glucose levels

53. Glucagon Action on Cells: Dominates in
Fasting State Metabolism

54. Targets of Glucagon Action
 Activates a phosphorylase, which cleaves off a
glucose 1-phosphate molecule off of glycogen.
 Inactivates glycogen synthase by phosphorylation
(less glycogen synthesis).
 Increases phosphoenolpyruvate carboxykinase,
stimulating gluconeogenesis
 Activates lipases, breaking down triglycerides.
 Inhibits acetyl CoA carboxylase, decreasing free
fatty acid formation from acetyl CoA
 Result: more production of glucose and substrates
for metabolism

55. Regulation of Glucagon Release
 Increased blood glucose levels inhibit glucagon
release.
 Amino acids stimulate glucagon release (high
protein, low carbohydrate meal).
 Stress: epinephrine acts on beta-adrenergic
receptors on alpha cells, increasing glucagon
release (increases availability of glucose for
energy).
 Insulin inhibits glucagon secretion.

56. Other Factors Regulating
Glucose Homeostasis
 Glucocorticoids (cortisol): stimulate
gluconeogenesis and lipolysis, and increase
breakdown of proteins.
 Epinephrine/norepinephrine: stimulates
glycogenolysis and lipolysis.
 Growth hormone: stimulates glycogenolysis and
lipolysis.
 Note that these factors would complement the
effects of glucagon, increasing blood glucose
levels.

57. Hormonal Regulation of Nutrients
Right after a meal (resting):
- blood glucose elevated
- glucagon, cortisol, GH, epinephrine low
- insulin increases (due to increased glucose)
- Cells uptake glucose, amino acids.
- Glucose converted to glycogen, amino acids
into protein, lipids stored as triacylglycerol.
- Blood glucose maintained at moderate levels.

58. A few hours after a meal (active):
- blood glucose levels decrease
- insulin secretion decreases
- increased secretion of glucagon, cortisol, GH,
epinephrine
- glucose is released from glycogen stores
(glycogenolysis)
- increased lipolysis (beta oxidation)
- glucose production from amino acids
increases (oxidative deamination;
gluconeogenesis)
- decreased uptake of glucose by tissues
- blood glucose levels maintained
Hormonal Regulation of Nutrients

59. Turnover Rate
 Rate at which a molecule is broken down and resynthesized.
 Average daily turnover for carbohydrates is 250 g/day.
 Some glucose is reused to form glycogen.
 Only need about 150 g/day.
 Average daily turnover for protein is 150 g/day.
 Some protein may be reused for protein synthesis.
 Only need 35 g/day.
 9 essential amino acids.
 Average daily turnover for fats is 100 g/day.
 Little is actually required in the diet.
 Fat can be produced from excess carbohydrates.
 Essential fatty acids:
 Linoleic and linolenic acids.

60. Regulation of Energy
Metabolism
 Energy reserves:
 Molecules that
can be oxidized for
energy are derived
from storage
molecules (glycogen,
protein, and fat).
 Circulating
substrates:
 Molecules absorbed
through small intestine
and carried to the cell
for use in cell
respiration.
Insert fig. 19.2

61. Pancreatic Islets (Islets of
Langerhans)
 Alpha cells secrete glucagon.
 Stimulus is decrease in blood
[glucose].
 Stimulates glycogenolysis and
lipolysis.
 Stimulates conversion of fatty
acids to ketones.
 Beta cells secrete insulin.
 Stimulus is increase in blood
[glucose].
 Promotes entry of glucose into
cells.
 Converts glucose to glycogen
and fat.
 Aids entry of amino acids into
cells.
VEDI
TRADUZIONE

62. Cellule alfa secernono glucagone.
Stimolo è Diminuzione del sangue [glucosio].
Stimola la lipolisi e glicogenolisi.
Stimola conversione degli acidi grassi a chetoni.
Le cellule beta secernono insulina.
Stimolo è Aumento nel sangue [glucosio].
Promuove l'ingresso del glucosio nelle cellule.
Converte il glucosio in glicogeno e grasso.
Aids ingresso di aminoacidi nelle cellule.
TRADUZIONE DIAPOSITIVA PRECEDENTE

63. Energy Regulation of Pancreas
 Islets of Langerhans contain 3 distinct cell
types:
 α cells:
 Secrete glucagon.
 β cells:
 Secrete insulin.
 ∆ cells:
 Secrete somatostatin.

64. Regulation of Insulin and
Glucagon
 Mainly regulated by blood [glucose].
 Lesser effect: blood [amino acid].
 Regulated by negative feedback.
 Glucose enters the brain by facilitated
diffusion.
 Normal fasting [glucose] is 65–105 mg/dl.

65. Regulation of Insulin and
Glucagon (continued)
 When blood [glucose] increases:
 Glucose binds to GLUT2 receptor protein in β cells,
stimulating the production and release of insulin.
 Insulin:
 Stimulates skeletal muscle cells and adipocytes to
incorporate GLUT4 (glucose facilitated diffusion
carrier) into plasma membranes.
 Promotes anabolism.

66. Oral Glucose Tolerance Test
 Measurement of
the ability of β
cells to secrete
insulin.
 Ability of insulin to
lower blood
glucose.
 Normal person’s
rise in blood
[glucose] after
drinking solution is
reversed to normal
in 2 hrs.
Insert fig. 19.8

67. Regulation of Insulin and
Glucagon
 Parasympathetic nervous system:
 Stimulates insulin secretion.
 Sympathetic nervous system:
 Stimulates glucagon secretion.
 GIP:
 Stimulates insulin secretion.
 GLP-1:
 Stimulates insulin secretion.
 CCK:
 Stimulates insulin secretion.

68. Regulation of Insulin and
Glucagon Secretion (continued)

69.  Glucose homeostasis – Putting it all together
Figure 26.8
Insulin
Beta cells
of pancreas stimulated
to release insulin into
the blood
Body
cells
take up more
glucose
Blood glucose level
declines to a set point;
stimulus for insulin
release diminishes
Liver takes
up glucose
and stores it as
glycogen
High blood
glucose level
STIMULUS:
Rising blood glucose
level (e.g., after eating
a carbohydrate-rich
meal) Homeostasis: Normal blood glucose level
(about 90 mg/100 mL) STIMULUS:
Declining blood
glucose level
(e.g., after
skipping a meal)
Alpha
cells of
pancreas stimulated
to release glucagon
into the blood
Glucagon
Liver
breaks down
glycogen and
releases glucose
to the blood
Blood glucose level
rises to set point;
stimulus for glucagon
release diminishes

70. Hormonal Regulation of
Metabolism
 Absorptive state:
 Absorption of energy.
 4 hour period after eating.
 Increase in insulin secretion.
 Postabsorptive state:
 Fasting state.
 At least 4 hours after the meal.
 Increase in glucagon secretion.

71. Absorptive State
 Insulin is the major hormone that promotes
anabolism in the body.
 When blood [insulin] increases:
 Promotes cellular uptake of glucose.
 Stimulates glycogen storage in the liver and muscles.
 Stimulates triglyceride storage in adipose cells.
 Promotes cellular uptake of amino acids and synthesis
of proteins.

72. Postabsorptive State
 Maintains blood glucose concentration.
 When blood [glucagon] increased:
 Stimulates glycogenolysis in the liver (glucose-6-
phosphatase).
 Stimulates gluconeogenesis.
 Skeletal muscle, heart, liver, and kidneys use fatty
acids as major source of fuel (hormone-sensitive
lipase).
 Stimulates lipolysis and ketogenesis.

73. Insert fig. 19.10
Effect of Feeding and Fasting
on Metabolism

74. Diabetes Mellitus
 Chronic high blood [glucose].
 2 forms of diabetes mellitus:
 Type I: insulin dependent diabetes (IDDM).
 Type II: non-insulin dependent diabetes (NIDDM).

75. Comparison of Type I and Type
II Diabetes Mellitus
Insert table 19.6

76. Type I Diabetes Mellitus
 β cells of the islets of Langerhans are destroyed
by autoimmune attack which may be provoked
by environmental agent.
 Killer T cells target glutamate decarboxylase in the β
cells.
 Glucose cannot enter the adipose cells.
 Rate of fat synthesis lags behind the rate of lipolysis.
 Fatty acids converted to ketone bodies, producing
ketoacidosis.
 Increased blood [glucagon].
 Stimulates glycogenolysis in liver.

77. Consequences of Uncorrected Deficiency
in Type I Diabetes Mellitus

78. Type II Diabetes Mellitus
 Slow to develop.
 Genetic factors are
significant.
 Occurs most often in
people who are
overweight.
 Decreased sensitivity to
insulin or an insulin
resistance.
 Obesity.
 Do not usually develop
ketoacidosis.
 May have high blood
[insulin] or normal
[insulin].
Insert fig. 19.12

79. Treatment in Diabetes
 Change in lifestyle:
 Increase exercise:
 Increases the amount of membrane GLUT-4 carriers in the skeletal muscle
cells.
 Weight reduction.
 Increased fiber in diet.
 Reduce saturated fat.
 TRADUZIONE:
 Cambiare stile di vita:
 Aumentare esercizio:
 Aumenta la quantità di GLUT-4 vettori nelle cellule del muscolo
scheletrico a membrana.
 La riduzione del peso.
 L'aumento di fibre nella dieta.
 Ridurre i grassi saturi.

80. Hypoglycemia
 Over secretion of insulin.
 Reactive hypoglycemia:
 Caused by an exaggerated
response to a rise in blood
glucose.
 Occurs in people who are
genetically predisposed to
type II diabetes.
 TRADUZIONE
 Oltre la secrezione di
insulina.
 Ipoglicemia reattiva:
 Causato da una risposta
esagerata a un aumento
del glucosio nel sangue.
 Si verifica in persone che
sono geneticamente
predisposti al diabete di
tipo II.
Insert fig. 19.13

81. Metabolic Regulation
 Anabolic effects of insulin are antagonized by
the hormones of the adrenals, thyroid, and
anterior pituitary.
 Insulin, T3, and GH can act synergistically to stimulate
protein synthesis.
 TRADUZIONE
 (Effetti anabolizzanti dell'insulina sono
antagonizzati dagli ormoni della ghiandole
surrenali, tiroide e dell'ipofisi anteriore.
 L'insulina, T3 e GH può agire in sinergia per
stimolare la sintesi proteica.)