Protein adipsin, which is produced in body fat, helps protect insulin-secreting cells called pancreatic beta cells from the destruction of type 2 diabetes, according to a new study by Weill Cornell Medicine andNewYork-Presbyterian researchers. Among middle-aged adults, higher levels of protein in the blood were also associated with protection against type 2 diabetes.
The study, published November 7 at Nature Medicine, may have implications for the future development of type 2 diabetes therapies that target and protect beta cells.
"The big problem with type 2 diabetes is that beta cells stop functioning properly and fade," said senior author Dr. James C. Lo, assistant professor of medicine and pharmacology at Weill Cornell Medicine and a cardiologist at NewYork-Presbyterian / Weill Cornell Medical Center . About 30 million people in the United States have diabetes, and up to 95% of those have a type 2 disease, in which the body stops responding to insulin, and pancreatic beta cells slowly stop producing enough.
Some of the currently available beta-targeting drugs have side effects, such as too much lowering of blood glucose, Dr. Lo said. In addition, there are no proven treatments to prevent beta cell loss. People with type 2 diabetes whose beta cells are not working properly must inject insulin to keep their blood glucose levels stable.
The team, which included researchers in the laboratories of Dr. Mingming Hao, Noah Dephoure and Dr. Lukas Dow of Weill Cornell Medicine, knew that adipsin had a role in stimulating beta cells to secrete insulin and theorized that this protein could be a potential therapy for diabetes type 2.
To investigate this theory, scientists first conducted a study in which they increased the levels of adipsin in type 2 diabetic mice. station. "Our findings in mice have shown that more adipsin in the blood translates to better diabetes control," said Dr. Lo.
Dr. Lo and his associates at Mount Sinai Icahn Medical School also studied human beta cells in their laboratories and found that adipsin activates a molecule called C3a that protects and supports the function of beta cells. They further discovered that C3a suppresses an enzyme called Dusp26 that can damage beta cells and cause them to die.
The researchers then directly blocked DUSP26 activity in human beta cells and found that this treatment protected beta cells from death. Similarly, when they suppressed DUSP26 activity in mice, beta cells became healthier, meaning they could better secrete insulin.
"I also hope that adipsin-targeted therapy or DUSP26 can prevent type 2 diabetes from developing beta-cell arrest and require insulin injections to treat it," said lead author Dr. Nicolás Gómez-Banoy, a postdoctoral fellow at Dr. Lo's lab.
To gain a better understanding of how adipsinmight affects the health of people in the community, the team worked with researchers at Harvard Medical School and Massachusetts General Hospital to evaluate 5570 individuals enrolled in the Framingham Heart Study, a current cardiovascular study conducted in Massachusetts.
Scientists have found that people with higher levels of adipsin in the blood had a lower incidence of diabetes in the future than people with lower levels. People with the highest adipsin level had a greater than 50% reduction in the incidence of diabetes compared with people with the lowest adipsin level.
In addition, adipsin levels correlate with the amount of subcutaneous adipose tissue stored just below the skin, not the visceral fat stored inside the abdomen. "Most people think that fat is associated with something bad, but it's more complicated than that," said Dr. Lo, who is also a fellow at the Weill Metabolic Health Center and the Cardiovascular Research Institute at Weill Cornell Medicine. "Subcutaneous fat is benign or even protective over visceral fat."
Further studies are needed to determine whether higher levels of adipsin in humans are protective against the development of diabetes and whether increasing adipsin levels will reduce the risk of developing diabetes in a given population.
Dr. Lo and his research team are currently investigating whether targeting and inhibiting the production of DUSP26 in beta cells may be a possible avenue for drug development.
"Hopefully this could be a new treatment option," Dr. Lo said.
Fat signal improves insulin secretion in diabetic mice, suggests potential therapy
Nicolás Gómez-Banoy et al., Adipsin stores beta cells in diabetic mice and is associated with protection against type 2 diabetes in humans, Nature Medicine (2019). DOI: 10.1038 / s41591-019-0610-4
Researchers unveil new potential approach to treating type 2 diabetes (2019, November 8)
retrieved 8 November 2019
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