The team found that mice with an excess of the protein Sirt1 in cells of the pancreas have improved glucose tolerance and enhanced insulin secretion in response to glucose. Glucose is the principal circulating sugar in the blood and the major energy source of the body.
"Mice with an increased amount of Sirt1 show a better response to high blood glucose levels that regularly occur after eating sweets, such as cookies or cakes," said Shin-ichiro Imai of Washington University School of Medicine. "The mice respond fast to high glucose by raising insulin levels, clearing the blood of the circulating sugar."
"Under normal feeding conditions, when glucose levels are lower, the mice with elevated Sirt1 appear normal," Imai added. "This is good news, suggesting that therapies designed to manipulate the amount of Sirt1 might improve insulin response in those with type 2 diabetes without causing other problems."
Pancreatic b cells have a highly coordinated mechanism that senses rises in blood glucose and converts that information into signals that increase the secretion of insulin, Imai explained. Insulin produced by the pancreas allows cells to take up glucose from the bloodstream and burn it for energy. A failure to make or respond to insulin in people with diabetes causes blood sugar levels to rise.
The researchers found that Sirt1 is present in pancreas cells that secrete insulin hormone. Mice genetically modified to have an excess of Sirt1 in b cells of the pancreas had improved glucose tolerance and enhanced insulin secretion in response to glucose.
The altered mice maintained their improved b ce ll function with age, they reported. Further analyses found that Sirt1 regulates genes involved in insulin secretion by b cells.
"Together, these results establish that an increase dosage of Sirt1 has beneficial effects on mammalian physiology," Imai said. "Our findings also provide new insight into the physiological and molecular functions of Sirt1 in glucose metabolism and suggest therapeutic interventions for the prevention and treatment of diabetes and other age-associated metabolic disorders."