The plant product quinic acid activates Ca²⁺‐dependent mitochondrial function and promotes insulin secretion from pancreatic beta cells

Abstract

Background and Purpose Quinic acid (QA) is an abundant natural compound from plant sources which may improve metabolic health. However, little attention has been paid to its effects on pancreatic beta‐cell functions, which contribute to the control of metabolic health by lowering blood glucose. Strategies targeting beta‐cell signal transduction are a new approach for diabetes treatment. This study investigated the efficacy of QA to stimulate beta‐cell function by targeting the basic molecular machinery of metabolism–secretion coupling. Experimental Approach We measured bioenergetic parameters and insulin exocytosis in a model of insulin‐secreting beta‐cells (INS‐1E), together with Ca2+ homeostasis, using genetically encoded sensors, targeted to different subcellular compartments. Islets from mice chronically infused with QA were also assessed. Key Results QA triggered transient cytosolic Ca2+ increases in insulin‐secreting cells by mobilizing Ca2+ from intracellular stores, such as endoplasmic reticulum. Following glucose stimulation, QA increased glucose‐induced mitochondrial Ca2+ transients. We also observed a QA‐induced rise of the NAD(P)H/NAD(P)+ ratio, augmented ATP synthase‐dependent respiration, and enhanced glucose‐stimulated insulin secretion. QA promoted beta‐cell function in vivo as islets from mice infused with QA displayed improved glucose‐induced insulin secretion. A diet containing QA improved glucose tolerance in mice. Conclusions and Implications QA modulated intracellular Ca2+ homeostasis, enhancing glucose‐stimulated insulin secretion in both INS‐1E cells and mouse islets. By increasing mitochondrial Ca2+, QA activated the coordinated stimulation of oxidative metabolism, mitochondrial ATP synthase‐dependent respiration, and therefore insulin secretion. Bioactive agents raising mitochondrial Ca2+ in pancreatic beta‐cells could be used to treat diabetes.

Gut Microbiota, Blood Metabolites, and Spleen Immunity in Broiler Chickens Fed Berry Pomaces and Phenolic-Enriched Extractives

“…In the present study, feeding with cranberry or wild blueberry pomaces significantly increased the QA level in the plasma of chickens. Thus, feed supplementation with cranberry and blueberry products could reduce oxidative stresses and improved metabolic functions against reactive oxygen species damage in chickens due to synergistic effects of multiple-phytochemical combinations of both berries ( 47 , 48 ).…”

Targeting Mitochondrial Calcium Uptake with the Natural Flavonol Kaempferol, to Promote Metabolism/Secretion Coupling in Pancreatic β-cells

“…While the impacts of Ca 2+ homeostasis [11,12] and mitochondrial function [13] on β-cell function are widely accepted, and despite the unquestionable role of mitochondrial Ca 2+ for pancreatic β-cell signal transduction [5][6][7], very few therapies or interventions based on the modulation of mitochondrial Ca 2+ have been developed until now. In this context, we recently demonstrated that natural bioactive quinic acid increases glucose-stimulated mitochondrial Ca 2+ rise, enhancing insulin secretion in both INS-1E β-cells and mouse islets, and improves glucose tolerance in mice [14]. In that study, quinic acid was not a direct activator of MCU but it enhanced the release of Ca 2+ from the endoplasmic reticulum, improving Ca 2+ transmission between the endoplasmic reticulum and mitochondria.…”

Nutritional value, physicochemical characterization and bioactive properties of the Brazilian quinoaBRS Piabiru

“…Pereira et al, 26 in a screening study on thirty-nine quinoa genotypes, also reported the presence of oxalic acid and, similarly, traces of fumaric acid; however, they did not detect quinic and malic acids. In a recent study performed by Heikkilä et al 32 in an in vivo mice model, it was suggested that quinic acid could be helpful in the treatment of diabetes, by promoting insulin secretion from pancreatic beta cells.…”