Health News and Research ...
Finding could lead to new
treatments for better blood glucose control
Researchers at the
Joslin Diabetes Center have shown for the first time
that insulin plays a key role in suppressing levels of
glucagon, a hormone involved in carbohydrate metabolism
and regulating blood glucose levels.
The study helps in the understanding of why those with
diabetes have high blood glucose levels and could lead to
development of a drug aimed at targeting glucagon levels.
"This is a very important finding because until now
scientists have only speculated that insulin may be involved
in keeping glucagon levels in check," said Rohit N.
Kulkarni, M.D., Ph.D., Principal Investigator in the
Joslin Section on Cellular and Molecular Physiology and
senior author of the study published in Cell Metabolism.
Produced by the alpha cells in the pancreas, glucagon acts
on the liver to help raise blood glucose when it becomes
low. It has the opposite effect on the liver as insulin,
which is released from pancreatic beta cells to lower blood
glucose when it is high. In a healthy individual, the two
counter each other to keep blood glucose levels balanced. In
individuals with long-standing type 1 or type 2
diabetes, inappropriate glucagon secretion can
increase the chances of hypoglycemia (low blood glucose
levels) and can interfere with insulin therapy.
The finding suggests that for people with either type 1 or
type 2 diabetes, a therapeutic approach could be developed
to target insulin receptors or proteins in alpha cells in
order to suppress glucagon secretion.
In addition, the research may also help in the understanding
of why patients with type 1 diabetes in particular,
who are required to inject insulin on a regular basis,
are at risk for hypoglycemia. It was thought that this
increased risk was linked in some way to insulin receptors
in the alpha cells, an idea that today's study suggests is
in fact the case, Dr. Kulkarni explained.
"This gives us some insight into the cause of hypoglycemia,
the most common complication in patients with type 1
diabetes," he said. "Injecting insulin leads to a decrease
in blood glucose. If it starts to go too low, glucagon
normally kicks in to prevent hypoglycemia. But, what happens
in diabetes is the alpha cells become desensitized by
repeated insulin injections over many years and they start
to behave abnormally. We believe this is linked to insulin
"This is the first genetic model wherein we provide
definitive proof that insulin is able to suppress glucagon
in mammals," Dr. Kulkarni said. "The next step is to
identify the specific proteins in alpha cells that could be
targeted to suppress glucagon secretion."
The paper concludes that the findings indicate there is a
significant role for insulin signaling in the regulation of
alpha cell functioning in both normal and hypoglycemic
conditions and provide direct genetic evidence for a key
role for insulin receptors in the modulation of pancreatic
alpha cell function.
Joslin Diabetes Center 04 09
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