Delphinidin Reduces Glucose Uptake in Mice Jejunal Tissue and Human Intestinal Cells Lines through FFA1/GPR40.

Jorge Hidalgo,Rafael Burgos,Francisco Morera,Stefanie Teuber,Carlos Flores,María Hidalgo,Camila Ojeda,Lucía Núñez,Carlos Villalobos

doi:10.3390/ijms18040750

Abstract

Anthocyanins are pigments with antihyperglycemic properties, and they are potential candidates for developing functional foods for the therapy or prevention of Diabetes mellitus type 2 (DM2). The mechanism of these beneficial effects of anthocyanins are, however, hard to explain, given their very low bioavailability due to poor intestinal absorption. We propose that free fatty acid receptor 1 (FFA1, also named GPR40), is involved in an inhibitory effect of the anthocyanidin delphinidin over intestinal glucose absorption. We show the direct effects of delphinidin on the intestine using jejunum samples from RF/J mice, and the human intestinal cell lines HT-29, Caco-2, and NCM460. By the use of specific pharmacological antagonists, we determined that delphinidin inhibits glucose absorption in both mouse jejunum and a human enterocytic cell line in a FFA1-dependent manner. Delphinidin also affects the function of sodium-glucose cotransporter 1 (SGLT1). Intracellular signaling after FFA1 activation involved cAMP increase and cytosolic Ca2+ oscillations originated from intracellular Ca2+ stores and were followed by store-operated Ca2+ entry. Taken together, our results suggest a new GPR-40 mediated local mechanism of action for delphinidin over intestinal cells that may in part explain its antidiabetic effect. These findings are promising for the search for new prevention and pharmacological treatment strategies for DM2 management.

Highlights

Intestinal glucose uptake control is a pharmacological target used for the control of hyperglycaemia [1]
The results showed that treatment with 100 μM delphinidin significantly inhibited the incorporation of 3-O-methyl-glucose [3H] (3-OMG) in the mouse intestine (Figure 1C), an effect that is similar to that of phlorizin 1 mM, a pharmacological inhibitor of the electrogenic transport of glucose, which was used as a positive control
We show new evidence suggesting that delphinidin could directly inhibit the total uptake of glucose in the gut via the free fatty acid receptor 1 (FFA1) receptor

Summary

Introduction

Intestinal glucose uptake control is a pharmacological target used for the control of hyperglycaemia [1]. An effective drug used as a first-line treatment in Diabetes mellitus type 2 (DM2), is accumulated in the mucosa of the intestine increasing glucose turnover and contributing to its antihyperglycaemic effect [2]. Since metformin increases intestinal glucose uptake and lactate production [4,5], this phenomenon can cause intolerance to the treatment [5] and contribute to the development of lactic acidosis [1]. Diet is considered a useful non-pharmacological strategy for the control of glycaemia [1]. Diet consumption of polyphenols such as anthocyanins has been associated with a lower risk of DM2 [6,7,8]

Methods

Results

Conclusion