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Identification of a Key Metabolic Regulator

Scientists have determined that the protein β-arrestin-2 plays critical roles in the pancreas and liver to regulate metabolism. β-arrestins are a family of proteins that regulate a wide variety of functions in different tissues in the body. Previous studies, in which mice were genetically engineered to lack β-arrestin-2, suggested that this protein might be involved in metabolic functions, but it remained unclear where β-arrestin-2 was needed to affect metabolism.

To explore a potential role for β-arrestin-2 in β cells (the pancreatic cells that produce insulin) and in hepatocytes (a cell type in the liver), the researchers genetically engineered mice to lack β-arrestin-2 specifically in β cells or in hepatocytes. The scientists found that male mice lacking β-arrestin-2 only in their β cells showed mild metabolic changes (compared to mice with β-arrestin-2 in their β cells) when fed a normal diet. These mice, however, showed significant metabolic changes when fed a diet that induces obesity and type 2 diabetes in mice. Compared to mice with β-arrestin-2 in their β cells consuming the same diet, the mice without β-arrestin-2 showed an increase in blood glucose (sugar) levels and almost no glucose-stimulated insulin secretion.

To complement these studies, the researchers also genetically engineered mice to have higher levels of β-arrestin-2 than usual. They found that, when fed the diabetes-inducing diet, these mice showed an increase in glucose-stimulated insulin secretion, greatly improved glucose tolerance, and lower blood glucose levels, compared to normal mice on the same diet. This suggested that β-arrestin-2 can counter the metabolic effects of a diet that induces obesity and type 2 diabetes. Importantly, the researchers found that glucose-stimulated insulin secretion was significantly reduced in a human pancreatic β cell line lacking β-arrestin-2, suggesting that β-arrestin-2 may be similarly important to human metabolism.

The researchers found that β-arrestin-2 has a similarly important role in hepatocytes: eliminating the protein in these liver cells in mice fed the diabetes-inducing diet worsened metabolic control, while increasing the protein’s levels in the cells helped ameliorate the effects of the diet.

These two studies implicate β-arrestin-2 as a key regulator of β cell and hepatic function in maintaining normal metabolism. Additional research will be necessary to determine the extent to which β-arrestin-2 acts similarly in humans, but this research suggest that strategies to promote β-arrestin-2 activity in β cells and/or hepatocytes could be clinically useful in the treatment of type 2 diabetes.

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