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Insulin signalling
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Insulin is secreted from the β cells of the islets of Langerhans – there are about 1-2 million per adult pancreas
Parasympathetic innervation of the β cells will induce insulin secretion
The pancreas
There is exocrine tissue: Acinar cells and duct
cells which secret fluid and enzymes into the
digestive tract
Acinar cells produce and transport enzymes
which are passed into the duodenum where they
assist with digestion – these cells also allow for
insulin transport
There are Endocrine cells: these are arranged
into spherical clusters within the islets of
Langerhans – α and β cells which secrete insulin
and glucagon

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There are several cells found in the Islets of Langerhans –
o The α cells which secrete Glucagon
o The β cells which secret Insulin
o The ε cells which produce the hormone Ghrelin (this is the hormone which induces hunger)
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Although the cells in the pancreas each have specific functions, they also have the ability to switch function
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This
would be useful in order to be able to treat Type 1 diabetes as these individuals have a very low count of
β cells
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Insulin response and the amount secreted changes constantly
depending other signals – there may be changes in the level of
Stimulation of Insulin release by blood glucose
insulin secreted from minute to minute
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Catecholamines are inhibitory factors of insulin – the receptors
The entry of glucose is mediated by GLUT2 (High Km ~20mM)
for these on the B cells are couples with G inhibitory protein
Glucokinase enzyme inside the cell will transform glucose into
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Nutrients are stimulatory to insulin
glucose-6-phosphate and so on through the glycolysis cycle
o Glucose, leucine and arginine – these can cause
This cycle produces ATP
Binding of ATP to K-ATP channels causes these channels to close
membrane depolarisation of the B cells which will
so there is depolarisation of the membrane
stimulate insulin secretion
4+5
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o Hormones – Glucagon, Incretins, Glucagon-like-peptide,
6
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Preproinsulin is produced in the Beta cells of the
islets of Langerhans
Preproinsulin has a 19 AA N-terminal sequence
which is hydrophobic, this drives the molecule to
the lumen of the ER
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Upon analysis it was found that a conserved lysArg sequence at the c terminal and Arg-Arg
sequence at the N terminal are conserved regions
which act as recognition sequences for the
protease
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Through human tumours in the islets of Langerhans
which caused an increased production of insulin
b
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This is independent of lifestyle and ethnic group
b
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People with this disease do not always need to administer insulin, depending on the type of MODY it may be that insulin
levels are lowered but still sufficient or that sulfonylurea drugs are able to close ATP receptors in order to allow insulin
release from the Beta cells
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There are 4 different types of MODY
Persistent Hyperinsulinemia Hypoglycaemia of Infancy (PHHI): K + ATP channel mutations → closed Management: Diazoxide
(opens K+ATP channel), or surgery
Type1 diabetes mellitus
Type 2 diabetes mellitus

Insulin Receptor
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Member of tyrosine kinase
family
Embedded in the membrane
Two alpha subunits and two
beta subunits
Alpha subunits are extra cellular
and contain insulin binding
domains
Two beta subunits are smaller
and penetrate through the
plasma membrane and contain
ATP-binding and tyrosine
kinase domains

Receptor Tyrosine Kinase
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Receptors do not contain a tyrosine kinase domain
On activation, these receptors cause the stimulation of a cytoplasmic tyrosine
kinase
Activation of the kinase leads to the propagation of the signal and target response
This class of receptor is referred to as Cytokine receptor superfamily – growth
Hormone receptor

The effect of insulin on tissues
Insulin has a pleiotropic effect on tissues:
i
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Promotes conversion of glucose to glycogen
iii
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Inhibits lipolysis
v
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Inhibits gluconeogenesis



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