Anatomy and histological of pancreas - Mahidol · 1 2 Islet of langerhans: Insulin, Glucagon...
Transcript of Anatomy and histological of pancreas - Mahidol · 1 2 Islet of langerhans: Insulin, Glucagon...
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Islet of langerhans:Insulin, Glucagon
Exocrine gland: enzymes
Anatomy and histological of Anatomy and histological of pancreaspancreas
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Islet of Islet of LangerhansLangerhans
A, α 20-30 % Glucagon
B, β 60-80% Insulin
D, σ ∼8% SomatostatinB cells
A cellsD cells
Parasympathetic fibers
Sympathetic fibers
F variable Pancreatic polypeptide
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Chain A: 21 aa
Chain B: 30 aa
Disulfide bridge
Insulin Peptide hormone
MW ∼6000
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Normal blood glucose ∼100 mg/dl (3-5 mM)Basal plasma insulin concentration ∼ 10 microU/mlNormal blood glucose ∼100 mg/dl (3-5 mM)Basal plasma insulin concentration ∼ 10 microU/ml
Meals
Insulin
Glucose
1 st phase
2 nd phase
Glucose
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Insulin processing
Insulin C peptide
Rough ER
Vesicle
Golgi
Processingin vesicles
Insulin secretion
Cleavage of proinsulin
Insulin : C peptide1:1
Insulin : C peptide1:1
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iii
i
i
Tolbutamide
K+
Ca++
[Ca++]
−ΔV
[ATP]/[ADP]
Glucose G-6-PGKGlucose Pyruvate
Mitochondria
Acetyl Co A
TCA
Electron transport chain
ATP
Glut 2
Glucose-stimulated insulin secretion mechanism
Hk
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Insulin secretionInsulin secretion
Non ATPdependent
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Insulin signalingInsulin signaling
Glucose transport
Protein synthesis
Lipid synthesis
glycogensynthesis
Growth and Gene expression
Insulin
Insulin receptor
a-subunit
b-subunit
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Insulin actionsInsulin actions
CHOGlycogen synthesis
GlycogenolysisGluconeogenesisHepatic glucose production
Protein
Amino acid uptake &protein synthesis
Amino acid output &amino acid oxidation
Lipid
Triglyceridesynthesis
Lipolysis
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Factor affecting insulin secretionFactor affecting insulin secretionFactor affecting insulin secretion
B cells
Insulin
• Amino acids• GI hormones• Diabetogenic H
• Glucose• Vagus N• Glucose• Vagus N
• a-Adrenergic• Insulin• Somatostatin
• a-Adrenergic• Insulin• Somatostatin
++
-
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Insulin deficitInsulin deficit Diabetes Diabetes MillitusMillitus
Absolute: Insulin dependent diabetes mellitus (IDDM)/ Type I ∼ 5-10%Relative: Non insulin dependent diabetes mellitus (NIDDM)/ Type II ∼ 90-95%
Defect in insulin secretionInsulin resistance
ReceptorPostreceptor
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•A casual plasma glucose level (taken at any time of day) of 200 mg/dL or greater when the symptoms of diabetes are present.
•A fasting plasma glucose value of 126 mg/dLor greater.
•An OGTT value in the blood of 200 mg/dLor greater measured at the 2-hour interval.
Diagnosis Diabetes MillitusDiagnosis Diabetes Diagnosis Diabetes MillitusMillitus
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Signs and symptoms of Signs and symptoms of diabetes mellitusdiabetes mellitus
Hyperglycemia Glucosuria(Osmotic diuresis)
Hyperlipidemia Ketonemia
Protein wasting Weight loss
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Insulin excessInsulin excessOver dose insulinInsulinoma
HypoglycemiaNeuroglycopenia
HungerDizzinessComa
Cathecolamine: anxiety, sweating, tachycardia
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GlucagonGlucagon
29 amino acids identical to enteroglucagonGlucagon act by binding to its receptor and activated G protein which cause an increase in cAMP. Glucagon has the effect of increasing blood glucose levels (opposite effect of insulin)
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GlucagonGlucagon actionsactions
CHOGlycogen synthesis
Glycogenolysis
GluconeogenesisHepatic glucose production
Lipid
Lipolysis
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Factor affecting Factor affecting glucagonglucagonsecretionsecretion
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Insulin and Insulin and glucagonglucagon cause the cause the tight control of blood glucose tight control of blood glucose
concentrationconcentration
CatecholaminesCorticosteroidsGrowth H
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GlucagonGlucagon excess and deficit are excess and deficit are rarerare
Glucagon excess: cancer of alpha cells (glucagonomas)
There is no report of glucagondeficit.
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SomatostatinSomatostatin
Somatotrophin-release inhibiting factor (SRIF)Also found in nerve terminals and other tissues.Somatostatin is a local inhibitor of insulin and glucagon secretion.Also function as a neurotransmitter/ neuromodulator in the control of moteractivity and cognitive functions.
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Pancreatic polypeptide (PP)Pancreatic polypeptide (PP)
36 amino acidsSecretion of PP is mainly under autonomic control.PP is released following feeding or during hypoglycaemiaRole of PP is still not understood.