Chicoric Acid and Chlorogenic Acid: Two Hydroxycinnamic Acids Modulate the Glucose 6-Phosphatase Activities in Pancreatic INS1 Beta-Cells—Novel Data in Favor of Two Putative Conformations of the G6Pase Within the ER Membrane

TL;DR

This study explores how two plant compounds affect the G6Pase enzyme in pancreatic beta-cells, suggesting the enzyme may have two different forms depending on glucose levels.

Contribution

The study proposes a novel bi-conformational model of G6Pase activity in beta-cells based on CRA and CGA effects.

Findings

CRA and CGA show inverse effects on G6Pase activity in INS1-beta-cells under varying glucose concentrations.

Data supports the existence of two putative G6Pase enzyme forms in the ER membrane.

The findings suggest an adaptive model of G6Pase modulation in response to glucose levels.

Abstract

Chicoric and chlorogenic acids (CRA and CGA), two caffeic acid derivatives found in a large variety of plants, particularly in Asteraceae, are known to modulate glucose-6-phosphatase (G6Pase) in hepatic and muscle cells. The aim of the present study is to use CRA/CGA to explore the modulation role and molecular mechanism of endocrine pancreatic beta-cells’ insulin secretion. The G6Pase enzyme activity influenced by caffeic and derivatives alone or in combination was assessed on microsomal fractions of INS1-beta-cells and hepatocytes. Overall, our results show inverse effects of CGA/CRA, allowing us to investigate the G6Pase activity modulation under low and high glucose concentrations. Our data strongly suggests the existence of two putative forms of the G6Pase enzyme. Based on these observations, we formulate the hypothesis of an adaptative bi-conformational model of G6Pase enzyme activity modulation depending on the level of the beta-cell glucose exposure.

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