The role of pancreatic beta-cell function and the impact of beta-cell failure on insulin production recently come under scrutiny by researchers. Because currently available therapies have been associated with hastening the failure of beta cells, the study’s findings that the protein adipsin can augment beta-cell insulin secretion and limit beta-cell death indicate that adipsin may be a valuable tool in the diabetic-treatment toolbox.
Cardiologist, senior author, and assistant professor of medicine and pharmacology at Weill Cornell Medicine Dr. James C. Lo, together with colleagues at Harvard Medical School and Massachusetts General Hospital, set out to explore that potential association. According to Dr. Lo, “A big problem associated with type 2 diabetes is that beta cells stop functioning properly and fade away.”
Initially exploring the role of the adipokine adipsin in mice, the team expanded their animal studies of adipsin to human beta cells and found that adipsin activates the molecule C3a, which prevents damage to, and death of, beta cells. The researchers subsequently discovered that C3a suppresses Dusp26, an enzyme that reduces the health of beta cells, resulting in beta-cell death.
In an effort to study the impact of adipsin on individuals in the general population, the research team evaluated 5,570 subjects already enrolled in the ongoing Framingham Heart Study, which is being conducted by Harvard Medical School and Massachusetts General Hospital. The researchers concluded that higher levels of adipsin in the blood were correlated with lower likelihood of developing diabetes, with those with the highest levels associated with a 50% or greater reduction in the incidence of diabetes when compared with those with the lowest levels of adipsin. Although they noted that “collectively, these data suggest that adipsin/C3a and DUSP26-directed therapies may represent a novel approach to achieve beta cell health to treat and prevent type 2 diabetes,” the researchers pointed out that further studies would be necessary to determine the effects of increased adipsin as a future avenue for drug development.
Another finding in this study of the Framingham Heart Study subjects was that there was a correlation between the level of adipsin and the amount of subcutaneous fat. Dr. Lo said, “Most people think that fat is associated with something bad, but it’s more complicated than that. Subcutaneous fat is more benign or even protective compared to visceral fat.”
Because type 2 diabetes is associated with insulin resistance and progressive loss of pancreatic beta-cell function and mass, the team theorizes that adipsin stimulation of beta cells, which results in insulin secretion, might be a potential new therapy for diabetic patients. “We hope this could be a novel treatment opportunity,” Dr. Lo said.
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