Electrophilic Agonists Modulate the Transient Receptor Potential Ankyrin-1 Channels Mediated by Insulin and Glucagon-like Peptide-1 Secretion for Glucose Homeostasis

Marisa Jadna Silva Frederico; Andreza Cipriani; Jocelyn Brice Alexandre Heim; Ana Karla Bittencourt Mendes; Marcela Aragón; Joana Margarida Gaspar; Nylane Maria Nunes De Alencar; Fátima Regina Mena Barreto Silva

doi:10.3390/ph16081167

Electrophilic Agonists Modulate the Transient Receptor Potential Ankyrin-1 Channels Mediated by Insulin and Glucagon-like Peptide-1 Secretion for Glucose Homeostasis

Pharmaceuticals (Basel). 2023 Aug 16;16(8):1167. doi: 10.3390/ph16081167.

Authors

Marisa Jadna Silva Frederico^{1

2}, Andreza Cipriani¹, Jocelyn Brice Alexandre Heim¹, Ana Karla Bittencourt Mendes¹, Marcela Aragón³, Joana Margarida Gaspar¹, Nylane Maria Nunes De Alencar², Fátima Regina Mena Barreto Silva¹

Affiliations

¹ Laboratory of Hormones & Signal Transduction, Departament of Biochemistry, Center of Biological Sciences, Campus Trindade, Federal University of Santa Catarina, Florianópolis 88040-900, SC, Brazil.
² Laboratory of Biochemistry and Pharmacology, Departament of Pharmacology and Physiology, Drug Research and Development Center (DRDC), Medical School, Federal University of Ceará, Rua Coronel Nunes de Melo, Fortaleza 60430-275, CE, Brazil.
³ Departament of Pharmacy, Science School, National University of Colombia, Bogotá 11011, Colombia.

Abstract

This pre-clinical study investigated the transient receptor potential ankyrin-1 (TRPA1) channels on modulating targets for glucose homeostasis using agonists: the electrophilic agonists, cinnamaldehyde (CIN) and allyl isothiocyanate (AITC), and the non-electrophilic agonist, carvacrol (CRV). A glucose tolerance test was performed on rats. CIN and AITC (5, 10 and 20 mg/kg) or CRV (25, 100, 300, and 600 mg/kg) were administered intraperitoneally (i.p.), and glycemia was measured. In the intestine, Glucagon-like peptide-1 (GLP-1) and disaccharidase activity were evaluated (in vivo and in vitro, respectively). Furthermore, in vivo and in vitro insulin secretion was determined. Islets were used to measure insulin secretion and calcium influx. CIN and AITC improved glucose tolerance and increased insulin secretion in vivo and in vitro. CRV was unable to reduce glycemia. Electrophilic agonists, CIN and AITC, inhibited disaccharidases and acted as secretagogues in the intestine by inducing GLP-1 release in vivo and in vitro and contributed to insulin secretion and glycemia. The effect of CIN on calcium influx in pancreatic islets (insulin secretion) involves voltage-dependent calcium channels and calcium from stores. TRPA1 triggers calcium influx and potentiates intracellular calcium release to induce insulin secretion, suggesting that electrophilic agonists mediate this signaling transduction for the control of glycemia.

Keywords: beta-cells; calcium; dissacharidase; glycemia; intestinal hormone; ionic channels; nutrients.

Grants and funding

This work was supported by grants from CNPq (305799/2019-3), the PPG-BQA/PNPD (2018/2019) fellowship for MJSF, and CAPES/PPG-Biochemistry (2018/019) for AC’s Ph.D fellowship.