Reduced levels of the VIP hormone in the pancreas due to poor nerve supply can contribute to the development of early diabetes in people with cystic fibrosis (CF), a study in mice suggests.
The study “VIP Reduction in the Pancreas of F508del-Homozygous CF Mice and Early Signs of Cystic Fibrosis Related Diabetes (CFRD)” was published in the Journal of Cystic Fibrosis.
A unique type of diabetes – known as cystic fibrosis-related diabetes (CFRD) – is a common complication for people with CF, especially in old age. CFRD is characterized by decreased production of insulin, a hormone secreted by the pancreas that lowers glucose in the bloodstream.
VIP (vasoactive intestinal peptide) is a hormone known to modulate insulin secretion in the presence of glucose. VIP is produced in the nervous system and functions as a signal molecule between nerve cells (neurotransmitters). It is also found in the respiratory, digestive, reproductive, and cardiovascular systems.
VIP also has anti-inflammatory and immunomodulatory properties and plays a vital role in maintaining clean airways.
Recently, researchers at Dalhousie University in Canada showed that VIP in the lungs, sweat glands, and small intestines of mice carrying the F508del-CFTR mutation, the most common mutation in people with CF, was 50% lower. This mutation leads to the production of a defective CFTR protein and is the underlying cause of CF.
This study found that VIP deficiency results from a decrease in nerve supply (innervation) from a young age, before signs of CF-like disease were observed.
In that study, the same team looked at whether VIP changes in the pancreas affected by nerve supply occurred at different stages of CF in the same mouse model to “determine whether changes in VIP levels would contribute to CFRD development,” wrote the team .
Based on their previous work, these mice showed minimal disease by eight weeks of age, while 17 week old mice showed well-developed CF-like disease.
The first series of experiments showed, compared to healthy control mice of the same age, that VIP was 51.2% lower in 8-week-old CF mice and 51.3% lower in the same animals after 17 weeks, in tissue isolated from the endocrine pancreas. This part of the pancreas secretes insulin along with glucagon, a hormone that, unlike insulin, increases glucose in the blood.
Likewise, in the part of the pancreas that secretes digestive enzymes known as the exocrine pancreas, VIP was reduced by 44.5% in 8 week old CF mice and decreased by 55.1% at week 17.
“All in all, these data show that the amount of VIP in the pancreas of CF mice is greatly reduced in both the early and late stages of the disease,” the researchers write.
Next, the team found that pancreatic endocrine and exocrine tissue from control mice had strong nerve supplies. In contrast, nerve supply in the endocrine tissue of 8-week-old mice was reduced by 58.8% and at 17 weeks of age by 49.4%. The nerve supply was also reduced in the exocrine tissue of CF mice of both ages, a statistically significant reduction after 17 weeks.
As a consequence, insulin production was significantly lower in both young and older CF mice compared to controls. In younger CF mice, insulin production was significantly reduced by 35%, while older mice showed a decrease of 38.7%. These results were confirmed using an alternative method of measuring insulin protein.
People with type 2 diabetes have higher levels of glucagon production. In the same way, this study showed high glucagon production in the pancreatic tissue of both 8 and 17 week old CF mice.
Finally, when evaluating the effects of altered insulin and glucagon production, the team found significantly higher levels of glucose in the blood of CF mice (210 mg per deciliter) compared to controls (141 mg per deciliter).
“Our results show a decrease in insulin and an upregulation of glucagon in the pancreas of CF mice, suggesting a CFRD phenotype [characteristic] can develop at an early stage (8 weeks of age) in the disease process, ”the scientists wrote.
“We suggest that low VIP levels, due to reduced innervation of the CF pancreas and starting at an early stage of the disease, contribute to changes in insulin and glucagon secretion that can lead to the development of CFRD,” they added.
