Fresh Clues to Origin of Diabetes Identified

by Thilaka Ravi on  October 14, 2010 at 12:50 PM Diabetes News   - G J E 4
Researchers 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.
 Fresh Clues to Origin of Diabetes Identified
Fresh Clues to Origin of Diabetes Identified

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

The study 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.

"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," said Peter Arvan, the study's senior author.

"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.

The findings were published online in the journal PLoS One.

Source: ANI

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