ENDOCRINE PANCREAS

Anatomy

• Location• Pancreatic Islets

(of Langerhans)– Alpha cells– Beta cells– Delta cells– F-cells

Hormones

Insulin

• Chemistry– Protein/Peptide

• 51 amino acids• 2-chains

&– 2 disulfide bridges

– Proinsulin• 86 amino acid

protein• C peptide• Peptidases

Insulin Action

Insulin Receptor

• Kinase

• Autophosphorylation

• Phosphorylation of proteins

• Translocation of GLUT-4

• Down-regulation

Glucose Transporter Proteins

• GLUT-1

• GLUT-2

• GLUT-3

• GLUT-4: INSULIN REGULATED

• GLUT-5

Basic effect of Insulin

• Promotes uptake of glucose from the blood

• Promotes storage of energy-producing nutrients

Effect of Insulin on the Liver

• Stimulates glycogenesis

• Stimulates protein synthesis

• Increased production of triglycerides, cholesterol, and VLDL

• Inhibits glycogenolysis

• Inhibits ketogenesis

• Inhibits gluconeogenesis

Effect of Insulin on Skeletal Muscle

• Promotes protein synthesis

• Stimulates glycogen synthesis

Effect of Insulin on Fat Cells

• Promotes triglyceride storage

Insulin Regulation• Factors that stimulate

insulin secretion– High serum glucose– High serum amino

acids– Enteric hormones

• Factors that inhibit insulin secretion– Glucagon– Somatostatin -adrenergic

stimulation

Insulin Control

-CELLPANCREATIC

ISLET

-CELLPANCREATIC

ISLET

SERUM GLUCOSESERUM GLUCOSE

LIVER &MUSCLELIVER &MUSCLE

GLUCOSEUPTAKE

GLUCOSEUPTAKE

GUTHORMONES

GUTHORMONESSERUM

AMINO ACIDS

SERUMAMINO ACIDS

GLUCAGONGLUCAGON

SOMATOSTATINSOMATOSTATIN

-ADRENERGIC-ADRENERGIC

INSULININSULIN

SERUM GLUCOSESERUM GLUCOSE

Glucagon

• Chemistry– 29 amino acid peptide– Proglucagon

• Action– Antagonizes the action of insulin– Acts primarily on the liver– Stimulates glycogenolysis– Stimulates gluconeogenesis– Stimulates ketogenesis

Glucagon Regulation

PANCREAS-CELL

PANCREAS-CELL

BLOODSUGARBLOODSUGAR

LIVER &MUSCLELIVER &MUSCLE

GLUCAGONGLUCAGON

GLUCOSEGLUCOSE

BLOODSUGARBLOODSUGAR

SOMATOSTATINSOMATOSTATIN

SYMPATHETICINNERVATIONSYMPATHETICINNERVATION

PARASYMPATHETICINNERVATION

PARASYMPATHETICINNERVATION

G-I HORMONESG-I HORMONES

CORTISOLCORTISOL

Somatostatin

• Chemistry– 14 amino acid peptide– Prosomatostatin– G-protein linked receptor– Produced and secreted by many tissues

• Action– Paracrine Factor– Inhibits insulin & glucagon secretion

• Regulation

Pancreatic Peptide

• Chemistry– 36 amino acid peptide

• Action– unknown

• Regulation– Serum levels increase after a meal, but

do not increase after glucose infusion– Vagotomy abolishes response to meal

Glucose Homeostasis

NORMALSERUM

GLUCOSE80-120 mg/dl

NORMALSERUM

GLUCOSE80-120 mg/dl

SERUM GLUCOSESERUM

GLUCOSE

SERUM GLUCOSE

SERUM GLUCOSE

ISLET-CELLS

ISLET-CELLS

LIVER &MUSCLELIVER &MUSCLE

METABOLICDEMANDS

METABOLICDEMANDS

INSULININSULIN

GLUCOSE UPTAKEGLUCOSE UPTAKE

ISLET-CELLS

ISLET-CELLS

LIVER &MUSCLELIVER &MUSCLE

GLUCAGONGLUCAGON

GLYCOGENOLYSIS

GLUCONEOGENESIS

GLYCOGENOLYSIS

GLUCONEOGENESIS

HYPERGLYCEMICHORMONES

HYPERGLYCEMICHORMONES

MEALSMEALS