Factor present in gestational and type 2 diabetes could provide new treatment options
New research reveals that both pregnant women with diabetes and type 2 diabetics have high levels of a fat metabolite that impairs pancreatic cells from secreting insulin. The findings, published recently in Cell Metabolism, suggest that blocking the effects of this metabolite may help prevent and treat diabetes.
In nearly one-fifth of pregnancies diabetes can arise, putting the woman at increased risk for developing type 2 diabetes later in life. To gain better insights into the shared mechanisms behind these two types of diabetes, researchers examined more than 340 molecules in blood samples from individuals with gestational diabetes, individuals with type 2 diabetes, and individuals without diabetes. The researchers used a metabolomics approach, which involves the study of chemical processes involving metabolites.
The team found that the blood of both gestational and type 2 diabetic patients contained a remarkable number of changed metabolites, including sugars, amino acids, and fats, compared with samples from the nondiabetic controls. One particular fat metabolite, CMPF, was dramatically increased in both gestational and type 2 diabetic individuals. Mouse experiments showed that this increased concentration of CMPF caused a decrease in insulin secretion from beta cells, which led to the development of diabetes.
More detailed mechanistic experiments revealed that CMPF enters a beta cell through what's called organic anion transporter 3 (OAT3). Once inside the cell it causes oxidative stress and other negative effects. Next, researchers found that the effects of CMPF could be prevented through either blocking the transport of CMPF into insulin-producing beta cells or treatment with antioxidants.
“We believe that CMPF and its transporter OAT3 represent novel targets for prevention and treatment of diabetes,” says first author Kacey Prentice, PhD candidate, Department of Physiology, University of Toronto. Read the article.
