Generating artificial pancreatic beta cells by using synthetic materials to mimic glucose-responsive insulin secretion in a robust manner holds promise for improving clinical outcomes in people with diabetes.
These results revealed that glucose-responsive insulin secretion is impaired when RAC1 is deficient in beta cells.
GLP-1 acts as an incretin hormone, which induces the stimulation of glucose-responsive insulin secretion and inhibition of glucagon secretion.
Compared with non-CF ferrets, newborn CF ferrets had fewer large islets and, in vitro, islets from newborn CF ferrets showed abnormal glucose-responsive insulin secretion, despite high insulin content.
Another compound that is widely used in diabetes research is glucagon-like peptide-1 (GLP-1), a multifunctional incretin hormone that inhibits glucagon secretion, induces glucose-responsive insulin secretion from β-cells, inhibits β-cell apoptosis and stimulates the proliferation of β-cells.
Incretins, glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) act on pancreatic β cells to stimulate glucose-responsive insulin secretion, but also have tissue-protective effects beyond lowering blood glucose levels [ 3], such as cardiovascular protection [ 4], anti-hepatic steatosis [ 5] and anti-Alzheimer's disease [ 6].
We measured glucose-responsive insulin secretion by using RAC1 knockdown INS-1 cells and found that high-glucose stimulation resulted in a significant decrease in insulin secretion in the RAC1 knockdown group (Fig. 3c), as is the case in pancreatic islets isolated from mice.
Previous reports found no activated RAC1 after high KCl stimulation and showed that when the mutant of inactivated RAC1 was transfected into the cells, glucose-responsive insulin secretion was inhibited without any influence on insulin secretion after high KCl stimulation [ 7].
Other studies suggest that BAD may regulate glucokinase activity in mitochondria and that BAD-deficient β-islet cells are less responsive with insulin secretion to glucose levels (Wikstrom et al. 2007).
Although GSK0660-treated cells were still glucose-responsive, they presented impaired insulin secretion function by releasing insulin at a lower efficiency.
This was associated with impairment of the following: GLP-1-stimulated cAMP production, phosphorylation of cAMP-responsive elements binding protein (CREB) and insulin secretion.
