Endocrine Pancreas

By
H.Khorrami Ph.D.
http://khorrami1962.spaces.live.com
khorrami4@yahoo.com
http://www.scribd.com/khorrami4
  Glycolysis   Gluconeogenesis
  Glycogenesis •  Alanine
  Lipogenesis •  Glutamine
•  glutamate
  Glycogenolysis
  Lipolysis
 Alpha cells; 25%;, glucagon
 Beta cells; 60%;, insulin
 Delta cells; somatostatin( SST)
 F cells; pancreatic polypeptide
 Preproinsulin in polyribosomes
 Proinsulin packed at the Golgi; 86 AA
 Proinsulin
•  Release is Ca dependent
•  7-8% of insulin biologic activity
•  HL: 30 min
 C-peptide
•  As marker of endogenous insulin
 6-10mg in pancreas
 2 mg/day
  C-peptide 31 AA + 2+2 connecting peptide
  51 AA
  5-8 min hl
  Portal concentration of insulin
•  Problem of exogenous insulin
  Autophosphorylation of the receptor
  Decrease cAMP
 Least variability
 Half life: 5-8 min
 Degrade in the liver by insulinase
 Systemic conc.=1/2 of conc. portal vein
  Glucose entrance
  Glu-6-phosphate
  Increase NADPH/ATP
  Phosphorylation and closing ATP-sensitive
K+ channel
  Ki rises
  Depolarization
  Voltage gated Ca channel open
  Increase Cai
  Fusion of insulin vesicles
  Exocytosis
STIMULATOR INHIBITOR
  A.A. esp. Argenine,   Somatostatin

Lysine,Ph.A.   Sympathetic
  FFA   Alpha-adrenergic
  Glucagon-like peptide
  GIP( gastric inhibitory
peptide)
  Gastrin
  Secretin
  CCK
  Parasympathethic
  Beta-adrenergic
  GH
 Glucose<50mg/dl……no insulin
 Glucose>250mg/dl……max insulin
 In the absence of insulin….depletion of
liver from glycogen in 4 hrs
 Facilitative glucose transporters
  GT-1 BBB,Rbc,fibroblast glu uptake +
  GT-2 liver,β cell, intestine low-affinity -
  GT-3 brain, fibroblast glu uptake ?
  GT-4 fat,skl.muscle,heart glu uptake +++
  GT-5 small intestine,sperm fruc.transp. ?
Active glucose transporters

 
  SGT-1 intestine, kidney intes.renal reabs -
  GT4
  Increase glucokinase activity in liver
  Stimulate lipoprotein lipase in endothelium of
capillaries of adipose tissue
  Glycolysis in adipose tissue
•  α-glycerophosphate for TG production

  Inhibits hormone-sensitive lipase (HSL)
  K entrance to liver and muscles
  Increase Na-K ATPase activity
 Mucosa of intestine
 Lens
 Rbc
 Renal tubules
 Liver
 Brain
•  Except: pituitary, hippothalamus, amygdala,
ventromedial & ventrolateral N.
 IRS-I& II
 Tyrosin kinase
 Autophosphorylation
 Decrease cAMP
INCREASE
  Glucokinase( glycogenesis)
  Phosphofructokinase( glycogenesis)
  Pyrovate kinase( lipogenesis)
  pyrovate dehydrogenase( lipogenesis)
  Acetyl-coA carboxylase
  Lipoprotein lipase, in endothelium of capillaries of
adipose tissue → FA enter adipose tissue
  Glycogen synthetase
  α-glycerophosphate → TG synthesis and storage
DECREASE
  Pyrovate carboxylase
  Glucose -6-phosphatase
  Fructose biphosphatase
  Phosphoenolpyrovate
  Phosphorylase
  Carboxykinase
  Hormone-sensitive lipase( HSL)( it hydrolyses TG to
glycerol and FA
STIMULATE INHIBIT
  Glu. Uptake by   Glycogenolysis

liver(indirect)   Gluconeogenesis
  Glycogenesis   Ketogenesis
  Glycolysis   Urea cycle activity
  F.A. synthesis   Proteolysis
  Uptake of leucine,   Lipolysis
isoleucine and valine by
muscle→ protein synthesis
  Na-K pump activity → K
+entrance to liver and
muscle
  Hormone-sensitive   Lipoprotein
lipase(HSL) lipase(LPL)
 Alanine
 Glutamine
 Glutamate
 Glucagon-related polypeptide( GRPP)
 Gucagon
 Glicentin(
enteroglucagon) 30-40% of
serum glucagon
•  GRPP+gluc+signal peptide
 Glucagon-like peptide
•  GLP-1
•  GLP-2
 29 AA
 HL…6min
 AC….cAMP….PK
 Phosphorylase
 Inactivation of glucokinase
 Catecholamine activity
 Cardiac muscle power
 Bile secretion
 Calcitonin secretion
STIMULATOR INHIBITOR
  Hypoglycemia   Insulin

  AA: Arginine, alanine   Hyperglycemia
  Stress   SST
  Exercise
  Sympatic
 Glycogenolysis
 Gluconeogenesis( liver uptake of
precursors)
 Lipolysis → ↑FFA
 β-oxidation of fats→
 NADH↑ →
 ↓oxydation of acetyl-coA →
 ↑ acetyl-coA →
• ↑ ketone body formation( can be used in brain)
• ↓glycolysis
 Prehormone ..28AA
 SST …14AA
 HL….2min
 Mostly paracrine effect
 Secreted from:
•  Pancreas
•  GI
•  Brain (HT)
STIMULATED BY INHIBITED BY
  Hyperglycemia   Insulin

  AA
  FFA
  CCK
  Glucagon
  Gut motility
  Gastric and pancreatic secretions
  Gastrin
  Secretin
  CCK
  GIP
  TRH
  Hcl secretion
  Gastric emptying
  GB contraction
  Splanchnic blood flow
  Insulin
  Glucagon
  Intestinal absorption of:
•  Glu, AA, fats . . .
 Secreted by F-cells
 36AA
 Inhibit:
•  Gallbladder contraction
•  Pancreatic exocrine secretion
 Stimulated by:
•  Ingestion of a protein-rich meal
•  Hypoglycemia
•  Strenuous exercise
 Cortisol
 GH
 Epinephrine
 Glucagon
 Contraceptives
 Prolactin& HPL
 Thyroid hormones
  Adrenergic stimulation
  Sweating
  Hunger
  Tremor
  Weakness
  Vertigo
  Lethargy
  Diplopia
  Behavioral changes
  Hypothermia
  Seizure
Glucagon Insulin Glu.uptak( Liver glu. Lipolysis
muscle) Prod.
Cat.amin ↑ ↓ ↓ ↑ ↑
Cortisol ↑ indirect↑ ↓ ↑ weak↑
GH ↑ ↓ ↑ ↑
 Insulin/glucagon ~ normally 2.3
 If I/G ↑→ cAMP↓→ anabolic state
 If I/G ↓→ cAMP↑→ catabolic state
 After 3 days starvation I/G…0.4
 If hi CH,low pr. Diet…. I/G…4
 Early onset
•  90% begins at 10-14 y
 Needexogenous insulin
 Damage of β-cell/Mϕ infiltration
•  Cytokins in early destruction
 Autoantibodies( autoimmune)
 Virally induced….transient
 HLA type..DR3,DR4(ch6)
 Ketosis
  Ketoacidosis
  HSL activity
•  Lipid mobilization
•  FFA↑
•  β-oxidation↑
  Ketogenesis
  Acidosis
  Anion gap ..(Na+K) – (Hco3+ cl)= normally 12-16meq/lit
  Hypovolemia
•  Lipoprotein lipase activity ↓
  Lipid clearance ↓
  VLDL ↑
•  LDL receptor ↓
  Cholesterol clearance ↓
  Hypercholesterolemia
•  Glycolysis ↓
 Serum insulin
•  Low, normal or hi
 No ketosis
 No association with HLA
 Mostly obese
 Mostly controlled by diet
 Insulin resistance
 Late onset
 30-40 year
 Do not need exogenous insulin
 Insulin resistance
 No ketosis
 No association with HLA
 85% obese
 Adiponectin
 A protein
 Derived from adipose tissue
 Plasma adiponectin reduced in obese
 Plasma adiponectin reduced in type-2
DM
 lower levels of adiponectin in SGA infants
may imply the very early development of
insulin resistance
 Nesfatin
 Leptin
•  Adipose-derived hormone
 Obestatin
•  Stomach-secreted hormone
 Insulin
resistance
 Metabolic syndrome
 Diabetes type 2
 You could have this condition for a long
time and not know it.
 People with severe insulin resistance
sometimes get dark patches of skin on
their necks, elbows, knees, hands, and
armpits
 Your chances of becoming insulin
resistant go up if you're overweight, don't
get enough exercise, have high blood
pressure, or you smoke
 Low HDL,
 High levels of TG
 Heart disease,
 a previous stroke, and blood vessel
disease in your neck or legs
 People with an African American,
Hispanic/Latino, Native American, Asian
American, or a Pacific Islander heritage
are more likely to become resistant to
insulin
 If your parent, brother, or sister has type
2 diabetes, your risk is higher
 If your mother had diabetes while she
was pregnant with you (gestational
diabetes), your risk also goes up
  Cut back on sweets, refined grains, and
animal fats, and have lots of vegetables,
fruits, and whole grains
  That kind of eating plan will help you get to
and stay at a healthy weight
  It also helps your cells use insulin better
  The DASH diet, for people with high blood
pressure, is a good example.
•  It includes cutting down on salt, too
•  It can lower insulin resistance, especially if you slim
down and become more active while you're at it
•  Studies have also shown a link between low vitamin
D and not using insulin well
 Physical activity goes a long way toward
fighting insulin resistance
 Like a healthy diet, it helps you lose
weight.
 Exercise also helps your cells use insulin,
especially in your muscles
 Aim for at least 30 minutes of activity a
day, most days of the week
  Your heart should beat faster, and you
should breathe a little harder
 People with insulin resistance often have
slightly higher levels of inflammation
throughout their bodies
 Other conditions have this inflammation,
too
 Insulin resistance is linked to heart and
blood vessel disease, blood clots in your
arteries, kidney disease, liver disease,
polycystic ovary syndrome (PCOS), and
rheumatoid arthritis
 Insulin resistance is part but not all of this
condition
 People with metabolic syndrome have at
least three of these traits:
•  a large waist, high triglycerides, low HDL
cholesterol, high blood pressure, and blood
glucose that is higher than normal
•  It raises your chances for diabetes, heart
disease, and stroke.
GLUC Insulin Muscle Liver glu. lipolysis
glu. production
uptake
Cat.amines
Inc. Dec. Dec. Inc. Inc.
Cortisol
Inc. Inc. Dec. Inc. inc.
GH
Inc. Dec. Inc. Inc.
  Serum Levels of Adiponectin and IGFBP-1 in
Short Children Born Small for Gestational
Age
  Refer to the site
  The levels of serum adiponectin were
significantly lower in the SGA than in AGA
children
  Adiponectin is a protein derived from
adipose tissue in humans, and serum
adiponectin levels are paradoxically
reduced in obese individuals

Endocrine Pancreas

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Endocrine Pancreas

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  A.A. esp. Argenine,   Somatostatin

Active glucose transporters

  Glu. Uptake by   Glycogenolysis

  Hypoglycemia   Insulin

  Hyperglycemia   Insulin

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Endocrine Pancreas

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Endocrine Pancreas

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 A.A. esp. Argenine,  Somatostatin

Active glucose transporters

 Glu. Uptake by  Glycogenolysis

 Hypoglycemia  Insulin

 Hyperglycemia  Insulin

S-ar putea să vă placă și

  A.A. esp. Argenine,   Somatostatin

  Glu. Uptake by   Glycogenolysis

  Hypoglycemia   Insulin

  Hyperglycemia   Insulin