2-(2-imidazolin-2-yl)-1-phenyl-1h-indole has been researched along with Insulinoma* in 2 studies
2 other study(ies) available for 2-(2-imidazolin-2-yl)-1-phenyl-1h-indole and Insulinoma
| Article | Year |
|---|---|
The imidazoline compound RX871024 promotes insulinoma cell death independent of AMP-activated protein kinase inhibition.
We have previously shown that the insulinotropic imidazoline compound RX871024 induces death of insulinoma MIN6 cells, an effect involving stimulation of c-Jun N-terminal kinase (JNK) and caspase 3. It has also been reported that AMP-activated protein kinase (AMPK) activates JNK and induces β-cell death. Here we show that RX871024, but not another insulinotropic imidazoline compound (BL11282), suppressed AMPK activity in MIN6 cells. The inhibitory effect of RX871024 on AMPK was supported by the observation that the imidazoline induced lipid droplet formation in the cytoplasm of MIN6 cells. This reflects stimulation of anabolic pathways and inhibition of catabolic pathways in the cell that happen under conditions when AMPK is inhibited. Activation of AMPK by 5-aminoimidazole-4-carboxamide riboside (AICAR) elevated basal and cytokine-induced death in primary β-cells and in insulinoma MIN6 cells. RX871024 aggravated AICAR-induced insulinoma MIN6 cell death regardless of the presence of pro-inflammatory cytokines. The specific cytotoxic effect of imidazoline compound RX871024 on insulinoma cell death but not primary β-cell death is independent of its action on AMPK and may suggest the possibility of using this type of compound in the treatment of insulinomas. Topics: Aminoimidazole Carboxamide; AMP-Activated Protein Kinases; Animals; Antineoplastic Agents; Cell Death; Cell Line; Imidazoles; Indoles; Insulin-Secreting Cells; Insulinoma; Mice, Obese; Phosphorylation; Ribonucleosides | 2016 |
Different modes of action of the imidazoline compound RX871024 in pancreatic beta-cells. Blocking of K+ channels, mobilization of Ca2+ from endoplasmic reticulum, and interaction with exocytotic machinery.
The imidazoline compound RX871024 glucose-dependently potentiates the release of insulin in pancreatic islets and beta-cell lines. This activity of the compound is not related to its action by stimulating alpha 2-adrenoceptors and I1- and I2-imidazoline receptors. There are at least three modes of action of RX871024 in beta-cells: (1) RX871024 blocks the ATP-dependent, Ca(2+)-activated, and delayed rectifier K+ channel activity; (2) RX871024 causes mobilization of Ca2+ from thapsigargin-sensitive intracellular stores, the effect probably controlled by cytochrome P450; and (3) the stimulatory activity of RX871024 on insulin release involves interaction of the compound with the exocytotic machinery, unrelated to the changes in membrane potential and cytoplasmic-free Ca2+ concentration, whereas protein phosphorylation plays an important role in this process. The maximal insulinotropic effect of RX871024 is much higher than that of the sulfonylurea glibenclamide. RX871024 stimulates insulin release and normalizes blood glucose levels in rats in vivo without affecting blood pressure and heart rate. Topics: Animals; Blood Glucose; Blood Pressure; Calcium; Cells, Cultured; Cytoplasm; Endoplasmic Reticulum; Exocytosis; Heart Rate; Imidazoles; Indoles; Insulin; Insulin Secretion; Insulinoma; Islets of Langerhans; Kinetics; Male; Membrane Potentials; Models, Biological; Pancreatic Neoplasms; Phosphorylation; Potassium Channel Blockers; Rats; Rats, Inbred SHR; Tumor Cells, Cultured | 1999 |