Pancreatic β‐cell: the beauty of being plastic


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906 Exp Physiol 97.8 (2012) pp 906–907

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Pancreatic β-cell: the beauty of
being plastic

Ernest Adeghate

Email: eadeghate@uaeu.ac.ae

Type 2 diabetes mellitus (T2DM) is a
chronic endocrine disorder affecting more
than 240 million people worldwide. The
prevalence of T2DM continues to rise in
many parts of the world, partly because a lot
of people are enslaved to a sedentary lifestyle
and inappropriate diet. Genetic factors also
play a role in whether an individual develops
T2DM or not. A strong interaction between
genetic and environmental factors in the
development of T2DM has been reported
(Adeghate et al. 2006). Irrespective of which
factor is to be blamed, the key molecule
in the pathogenesis of T2DM is insulin.
It is a major hormone of the endocrine
pancreas that plays an important role in the
metabolism of carbohydrate, but also has a
say in how protein and fat are utilized.

Optimal insulin secretion and action
are crucial to the maintenance of
normoglycaemia. In the absence of intact
and adequate insulin, an individual is
condemned to developing T2DM. What,
then, is the driving force behind the
secretion and effective insulin molecule?
The pancreatic β-cell of the islets of
Langerhans must be viable and in sufficient
numbers and mass to be able to produce
intact insulin in adequate quantities. An
ideal pancreatic β-cell that will not put an
individual in danger of developing T2DM
must also be smart enough to adapt to the
variations in the level of blood glucose in
a timely and calibrated manner. It must
also be able to maintain normoglycaemia
during a variety of endeavours ranging
from intense physical activity to fasting.
The plasticity of insulin release in different
metabolic conditions has been examined
largely in small animal models (Del Zotto
et al. 2004; Alonso et al. 2007). However,
the mechanism by which insulin plasticity
is executed is complex and has been poorly
understood.

The article by Gartford et al. (2012) in the
May issue of Experimental Physiology used
sheep, a large-animal model, to examine
the mechanisms of insulin plasticity. This
is the first time that a large-animal model,
with a semblance of human size, has been
used to investigate how pancreatic β-cell
plasticity is achieved. Gatford et al. (2012)
provide compelling evidence that the sheep
model adapted to 16 days of continuous,
moderate hyperglycaemia by increasing
glucose and arginine-induced insulin
release rather than initiating an increase in
pancreatic cell mass. Their findings were
supported by techniques such as steady-
state infusion, immunofluorescence (for
β-cell mass) and radioimmunoassay (for
insulin). Insulin sensitivity, blood glucose
level, glucose tolerance, body composition
and growth of several organs were
also determined. This novel observation
contradicts previous reports, where large
and significant increases in pancreatic β-
cell mass were observed after rodent models
were challenged with hyperglycaemia
(Alonso et al. 2007).

The article by Gatford et al. (2012) shows
that pancreatic β-cells are smarter than
previously thought, because they respond to
chronic glucose challenge by working more
efficiently rather than initiating an increase
in number. This appears to make sense,
because it is physiologically easier for the
body to handle variations in function than
accumulated cell mass. What would the islet
do with the extra pancreatic β-cells when
the individual is fasting or exposed to low
glucose levels?

More importantly, Gatford et al. (2012)
showed, for the first time, that insulin
sensitivity was not altered in the course of
chronic glucose challenge. This is in sharp
contrast to reports on rodent models, where
a significant decrease in insulin sensitivity
was observed after a glucose load (Topp et al.
2004).

This is a change in paradigm in the way
the plasticity of the pancreatic β-cell is
viewed. The conclusion of the study has a
wider ramification, because plasticity has
also been observed in other cell types.
It is well known that neurons can adapt

to different environmental conditions and
produce novel transmitters if and when
challenged by a new millieu.

What could be the way forward in further
exploring the mechanism(s) by which
pancreatic β-cells adapt to changes in the
level of blood glucose? The limit of the
plasticity of pancreatic β-cells will also be of
interest in future studies. For example, how
would the β-cell respond in an environment
of constant and severe hyperglycaemia,
ageing and many other epigenetic and
environmental factors? A look at a different
animal model may also be helpful in the
search for a better understanding of the
plasticity of pancreatic β-cells. The sheep
is a ruminant and may therefore, not
experience the wide variations in blood
glucose concentrations seen in humans,
because of a constant and trickle supply of
energy substrates from the gastrointestinal
tract. The use of pig might be a preferred
model because they are omnivores, have
a similar size and eat sporadically like
humans.

The study by Gatford et al. (2012) shows
that further research into the mechanism
of pancreatic β-cell plasticity will probably
focus more on the functional aspect of
insulin release and its effect on target
cells rather than on an increase in cell
mass. Transcriptomic, proteomic and/or
peptidomic approaches that examine the
nature and function of genes expressed
and of proteins/peptides released by
pancreatic β-cells after exposure to chronic
hyperglycaemia may be used to address the
molecular basis of the issues raised in this
valuable sheep model.

References

Adeghate E, Schattner P & Dunn E (2006). An
update on the etiology and epidemiology of
diabetes mellitus. Ann N Y Acad Sci 1084,
1–29.

Alonso LC, Yokoe T, Zhang P, Scott DK, Kim
SK, O’Donnell CP & Garcia-Ocaña A (2007).
Glucose infusion in mice: a new model to
induce β-cell replication. Diabetes 56,
1792–1801.

DOI: 10.1113/expphysiol.2012.064766 C© 2012 The Author. Experimental Physiology C© 2012 The Physiological Society



Exp Physiol 97.8 (2012) pp 906–907 Pancreatic β-cell: the beauty of being plastic 907

Del Zotto H, Borelli MI, Flores L, Garcı́a ME,
Gómez Dumm CL, Chicco A, Lombardo YB
& Gagliardino JJ (2004). Islet neogenesis: an
apparent key component of long-term
pancreas adaptation to increased insulin
demand. J Endocrinol 183, 321–330.

Gatford KL, De Blasio MJ, How TA, Harland
ML, Summers-Pearce BL & Owens JA (2012).
Testing the plasticity of insulin secretion and
β-cell function in vivo: responses to chronic
hyperglycaemia in the sheep. Exp Physiol 97,
663–675.

Topp BG, McArthur MD & Finegood DT (2004).
Metabolic adaptations to chronic glucose
infusion in rats. Diabetologia 47,
1602–1610.

C© 2012 The Author. Experimental Physiology C© 2012 The Physiological Society