1 2

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

8

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

19 20

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.