Human Diabetes Gene Protects Against the Disease in Mice
When researchers at the University of Bergen inserted a diabetes gene into mice, they were surprised by the result. The mouse pancreas was severely injured, but the animals were still protected against diabetes.
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Twenty years ago, a family with a completely new form of hereditary diabetes was discovered in Norway. The disease is caused by a gene mutation and was named MODY8.
MODY8 is a rare condition where patients, in addition to diabetes, develop an inflamed pancreas. Patients are not aware of this inflammation when the disease is discovered but, eventually, they experience diarrhea and abdominal pain.
There is no cure for MODY8. The patients take insulin for their diabetes and painkillers and capsules containing digestive enzymes for their digestive problems.
Researchers at the University of Bergen have long tried to create a mouse model for MODY8 to improve understanding of the disease and provide patients with better treatment options.
They have now succeeded, and the mouse model was recently published in Gastroenterology, the leading scientific journal in digestive diseases.
Surprising results
But the result was not as expected. The gene mutation caused the mice to develop inflammation in the pancreas just like in the patients, but there was no diabetes.
Even though the pancreas of the mice was severely injured over time, the cells that produce insulin managed to survive, and the blood sugar was actually regulated somewhat better than in healthy mice.
"This was a very surprising finding," says Anny Gravdal Svanbring. She is the first author of the study and part of the research group that created the mouse model.
"MODY8 is a disease where all individuals with the genetic defect develop diabetes," she explains. Diabetes is also the main reason patients seek medical attention.
Why?
"We know from previous research that the MODY8 mutation leads to accumulation of a digestive enzyme, which is toxic to pancreatic cells," says researcher Karianne Fjeld. She led the study together with professor Anders Molven.
"When we culture cells in the laboratory, we see that cells exposed to the damaged digestive enzyme become stressed and die," Fjeld further explains.
"But how can the mice then be protected? Why don't they develop diabetes despite their injured pancreas? These are the exciting questions the researchers want to answer now.
Can the mouse model still be useful?
Mice are the most common animal model in diabetes research, but the results from Bergen show that there can be significant differences in how the disease develops compared to humans.
"We know that mice and humans have a wide range of anatomical and physiological differences. After all, it has been at least 70-80 million years since we diverged during the evolution of mammals," says Molven.
One theory is that MODY8 mice produce fat or other substances in the pancreas to shield the insulin-producing cells from the damaged digestive enzyme.
Can knowledge of these differences help us combat diabetes in humans in the future? This question is what the researchers at UiB now will pursue.
Reference:
Gravdal A, Wilhelm SJ, CEL-MODY Mouse Project, Lowe ME, Molven A, Xiao XK, Fjeld K. The MODY-Causing Mutation of the Human Carboxyl Ester Lipase Gene (CEL) Triggers Chronic Pancreatitis but not Diabetes in Mice
Gastroenterology. 2025. doi: 10.1053/j.gastro.2025.01.243.
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