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Pancreas
Exocrine pancreas
Digestive enzymes
Endocrine pancreas
Insulin
Glucagon
Somatostatin
Pancreatic polypeptide
Secretory Products
A cell ()
B cell ()
D cell ()
Somatostatin
Processing of Insulin
Preproinsulin
Preproinsulin is a long-chain polypeptide (MW 11,500) produced
by mRNA-directed translation in the rough endoplasmic reticulum.
Proinsulin
Preproinsulin is cleaved immediately after synthesis to proinsulin
(MW 9000). Proinsulin is transported to the Golgi and packaged into
secretory granules.
Insulin and C peptide
Maturation of the secretory granule involves proteolytic cleavage of
proinsulin into insulin and C peptide. Normal mature secretory
granules contain these in equimolar amounts and only small
quantities of proinsulin.
Insulin hexamer
with two Zn atoms
Glucose Transporters
All cells require proteins to transport glucose across the lipid
bilayers into the cytosol.
The intestine and kidney have an energy dependent
Na+/glucose cotransporter.
All other cells have non-energy dependent transporters that
facilitate diffusion of glucose from a higher concentration to a
lower concentration across cell membranes. At least five
facilitative glucose transporters have been described, and
these have different affinities for glucose (GLUT1, GLUT2,
GLUT3, GLUT4, and GLUT5).
Affinity for
glucose
GLUT1
High
GLUT2
Low
GLUT3
High
GLUT4
Medium
GLUT5
Medium
Insulin Receptors
Insulin action begins with the binding to specific cell surface
receptors.
Insulin receptors are membrane glycoproteins composed of
two subunits: a larger subunit which extends beyond the
cell surface and is involved in the binding of insulin, and a
smaller subunit which is predominately intracellular and
contains tyrosine kinase activity.
Upon insulin binding, signal transduction results in
autophosphorylation of the receptor tyrosine kinase. This
now activated complex, interacts with and phosphorylates a
network of as many as nine intracellular proteins.
Muscle
Increases ribosomal protein synthesis
Increases amino acids uptake
Increases glucose transport
Increases glycogen synthesis and inhibits glycogen breakdown
Adipose tissue
Increases triglyceride storage
Inhibits intracellular lipase
Promotes uptake of fatty acids
Increases glucose transport
Reduces fatty acid flux to the liver
Target enzyme
Glucose transporter
Glucokinase
Glycogen synthase
Glycogen phosphorylase
Phosphofructokinase-1,
pyruvate dehydrogenase
complex
Acetyl-CoA carboxylase
Lipoprotein lipase
Glucagon
Synthesized in the A cells of the Islets of Langerhans, the
precursor molecule, proglucagon, is composed of 160 amino
acids. Within this prohormone are several other peptides
connected in tandem:
glicentin-related polypeptide (GRPP)
glucagon
glucagon-like peptide-1 (GLP-1)
glucagon-like peptide-2 (GLP-2)
Secretion of glucagon
The release of glucagon is controlled primarily through suppression
by glucose and insulin.
Glucagon secretion is inhibited by glucose. This may be direct, or
indirect via the release of insulin and somatostatin.
Several hours after the intake of dietary carbohydrates, blood
glucose levels fall below 4.5 mM and trigger the secretion of
glucagon. Basically, this signal says: glucose is gone.
Glucagon Receptors
The liver is one of the major target organs for glucagon.
Glucagon binds to hepatic receptors in the cell membrane
and stimulates adenylyl cyclase and thus increases the
intracellular concentration of cAMP.
Target enzyme
Glycogen phosphorylase
Glycogen synthase
Glycolysis (liver)
Phosphofructokinase-1
Gluconeogenesis (liver)
Fructose-1,6-bisphosphatase
Pyruvate kinase
Triacylglycerol lipase
Steroid hormones
production
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