[acb-diabetics] scientists reveal new reaason for development of diabetes

[Patricia LaFrance-Wolf]

Scientists Reveal New Clues to Origin of Diabetes

 

Scientists have identified events inside insulin-producing pancreatic cells
that set the stage for a neonatal form of non-autoimmune Type 1 diabetes,
and

may play a role in Type 2 diabetes as well.... 

 

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Scientists have identified events inside insulin-producing pancreatic cells
that set the stage for a neonatal form of non-autoimmune Type 1 diabetes,
and

may play a role in Type 2 diabetes as well. 

 

The study from the University of Michigan scientists has pointed to a
potential target for drugs to protect normally functioning proteins
essential for

producing insulin. This shows that certain insulin gene mutations involved
in neonatal diabetes cause a portion of the proinsulin proteins in the
pancreas'

beta cells to misfold. 

 

Proinsulin proteins are the precursors of insulin, which the body needs to
regulate blood sugar levels. Crucially, the misfolded mutant proteins cause
normal

proinsulin proteins in beta cells to misfold as well, the scientists found
in studies of mouse and rat beta cells. 

 

Peter Arvan, the study's senior author explained that, once the 'good'
proinsulin turns 'bad,' it cannot be made into insulin and so the beta
cells, and

then the whole animal, become insulin deficient. The insulin deficiency
causes diabetes and from there, things get worse and worse. "In all
diabetes, beta

cells don't perform to the level needed. It's possible that the beta cell
failure of Type 2 diabetes also has a critical protein folding component." 

 

"The question is, can you reach a point in ordinary diabetes where
misfolding causes the problem we have identified?" he said.  

 

In lab dish cultures of normal rat and mice beta cells, the scientists
introduced single gene mutations known to be involved in various types of
neonatal

diabetes. They consistently found that misfolding occurred in normal
proinsulin protein when mutant proinsulin protein was present. They also
observed

the same aberrant events in the pancreatic beta cells of Akita mice, a mouse
model with the same mutation that occurs in a human family with neonatal
diabetes. 

 

Protein folding is a phenomenon that has drawn a lot of recent attention
from scientists who believe it plays a role in several common diseases. 

 

Diabetes researchers currently lack a clear picture of why beta cells in the
pancreas fail in diabetes. Many researchers look at stress and the stress
response

from the beta cells' endoplasmic reticulum or ER, a structure that
transports materials within the cell. Stress in this structure occurs in
diabetes, along

with reduced beta cell mass. 

 

The study found that each of the mutations examined led to ER stress and the
ER stress response in beta cells, but that these ER events alone could not

block insulin production in normal beta cells and do not appear to be the
origin of the insulin deficiency. They hypothesize that protein misfolding
events

first block insulin production and cause insulin deficiency, leading to
diabetes.

 

Published online in the journal PLoS One, Oct. 2010

 

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