capsazepine and Insulinoma

[6]-shogaol is a vanilloid compound present in steamed ginger (Zingiber officinale), a commonly used spice. Pancreatic beta-cells respond to nutrients like glucose, amino acids and fatty acids, by an increase in the cytoplasmic free Ca²⁺ concentration ([Ca²⁺](i)), which mediates diverse cellular processes in these cells. Some vanilloid compounds activate the transient receptor potential vanilloid receptor type 1 (TRPV1) channel.. We investigated whether [6]-shogaol could trigger Ca²⁺ signals in the beta-cell.. [Ca²⁺](i) was measured from single INS-1E cells by microscope-based fluorometry using fura-2 as the Ca²⁺ indicator.. In fura-2 loaded single rat insulinoma INS-1E cells, a widely used model of beta-cell, [6]-shogaol increased [Ca²⁺](i) in a concentration-dependent manner. [Ca²⁺](i) increase by [6]-shogaol was completely blocked when Ca²⁺ was omitted from the extracellular medium. Capsazepine, an inhibitor of the TRPV1 ion channel completely inhibited the [6]-shogaol-induced [Ca²⁺](i) increase. [Ca²⁺](i) increase obtained by 1 µM [6]-shogaol was greater than that obtained by 10 mM glucose. Moreover, a sub-stimulatory concentration of [6]-shogaol (300 nM), significantly enhanced the glucose-induced [Ca²⁺](i) increase in these cells.. We conclude that [6]-shogaol induces Ca²⁺ signals in the beta-cell by activating the TRPV1 channels, and it sensitizes the beta-cells to stimulation by glucose.

Topics: Animals; Calcium Signaling; Capsaicin; Catechols; Cell Line, Tumor; Clone Cells; Dose-Response Relationship, Drug; Glucose; Insulinoma; Islets of Langerhans; Pancreatic Neoplasms; Rats; TRPV Cation Channels

Capsaicin-sensitive afferent neurons including transient receptor potential vanilloid subfamily 1, TRPV1, and neurohormonal peptides participate in the physiological regulation of pancreatic endocrine. However, the direct effect of capsaicin on insulin secretion remains unknown. Our present study showed that TRPV1 is expressed in islet beta cells as well as in neurons in rat pancreas, and also in rat beta cell lines, RIN and INS1. Capsaicin (10(-11)-10(-9) M) dose-dependently increased insulin secretion from RIN cells, and this effect was inhibited by either a TRPV1 inhibitor capsazepine or EDTA. Systemic capsaicin (10 mg/kg, s.c.) increased plasma insulin level 1 h after the treatment. We demonstrated for the first time that TRPV1 is functionally expressed in rat islet beta cells and plays a role in insulin secretion as a calcium channel. This study may account for the influences of capsaicin on the food intake and energy consumption as well as on the pathophysiological regulation of pancreatic endocrine.

Topics: Animals; Capsaicin; Cell Line, Tumor; DNA Primers; Ganglia, Spinal; Gene Expression Regulation; Insulin; Insulin Secretion; Insulinoma; Ion Channels; Islets of Langerhans; Male; Pancreatic Neoplasms; Rats; Rats, Sprague-Dawley; Receptors, Drug; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; TRPV Cation Channels