Inositol hexakisphosphate kinase 1 is a metabolic sensor in pancreatic β-cells.

ABSTRACT: Diphosphoinositol pentakisphosphate (IP₇) is critical for the exocytotic capacity of the pancreatic β-cell, but its regulation by the primary instigator of β-cell exocytosis, glucose, is unknown. The high K_m for ATP of the IP₇-generating enzymes, the inositol hexakisphosphate kinases (IP6K1 and 2) suggests that these enzymes might serve as metabolic sensors in insulin secreting β-cells and act as translators of disrupted metabolism in diabetes. We investigated this hypothesis and now show that glucose stimulation, which increases the ATP/ADP ratio, leads to an early rise in IP₇ concentration in β-cells. RNAi mediated knock down of the IP6K1 isoform inhibits both glucose-mediated increase in IP₇ and first phase insulin secretion, demons

SUBMITTER: Rajasekaran SS 

PROVIDER: S-EPMC5899964 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature