Stimulation of insulin release from the MIN6 cell line by a new imidazoline compound, S‐21663: evidence for the existence of a novel imidazoline site in β cells

@article{Brigand1997StimulationOI,
  title={Stimulation of insulin release from the MIN6 cell line by a new imidazoline compound, S‐21663: evidence for the existence of a novel imidazoline site in $\beta$ cells},
  author={Laurence Brigand and Anne Virsolvy and Karine Peyrollier and Dominique Manechez and J. J. Godfroid and Beatrice J. Guardiola-Lemaitre and Dominique Bataille},
  journal={British Journal of Pharmacology},
  year={1997},
  volume={122}
}
1 The MIN6 cell line derived from in vivo immortalized insulin‐secreting pancreatic β cells was used to study the insulin‐releasing capacity and the cellular mode of action of S‐21663, a newly synthesized imadizoline compound known for its antidiabetic effect in vivo and its ability to release insulin from perfused pancreas. 2 S‐21663, at concentrations ranging from 10−5 M to 10−3 M was able to release insulin from MIN6 cells; its activity peaked at 10−4 M, a drop in the stimulant factor being… 
In vitro mechanism of action on insulin release of S‐22068, a new putative antidiabetic compound
TLDR
It is concluded that S‐22068 is a novel imidazoline compound which stimulates insulin release via interaction with an original site present on the Kir6.2 moiety of the β cell KATP channels.
Novel I1-Imidazoline Agonist S43126 Augment Insulin Secretion in Min6 Cells
TLDR
It is concluded that S43126 exerts its insulinotropic effect in a glucose dependent manner by a mechanism involving L-type calcium channels and imidazoline I1-receptors.
Novel I 1-Imidazoline Agonist S 43126 Augment Insulin Secretion in Min 6 Cells
The I1-imidazoline receptor is a novel drug target for hypertension and insulin resistance which are major disorders associated with Type II diabetes. In the present study, we examined the effects of
Multiple effector pathways regulate the insulin secretory response to the imidazoline RX871024 in isolated rat pancreatic islets
TLDR
The results suggest that RX871024 exerts multiple effects in the pancreatic β‐cell and that its effects on insulin secretion cannot be ascribed only to interaction with a putative imidazoline binding site.
Stimulation of insulin secretion in clonal BRIN-BD11 cells by the imidazoline derivatives KU14r and RX801080.
TLDR
It is concluded that, rather than acting as antagonists of imidazoline-induced insulin secretion, the imidrazoline derivatives KU14R and RX801080 are themselves potent insulinotropic agents.
Heterogeneous characteristics of imidazoline-induced insulin secretion
TLDR
The characteristics of phentolamine-induced secretion appear to be attributable to the consequences of KATP channel closure, while there are additional mechanisms involved in the action of idazoxan and alinidine, which may contribute to the obvious differences in the characteristics of secretion.
Effect of acute and sub-chronic administration of the imidazoline compound S 22068 on in vivo glucose and insulin responses in normal lean CBA/Ca mice.
TLDR
It is suggested that S 22068 is similar in effect to metformin, and is not insulinogenic, in contrast to the sulfonylureas or putative I(3) imidazoline site ligands.
Clonidine-displacing substance and its putative role in control of insulin secretion: a minireview.
  • S. Chan
  • Biology, Chemistry
    General pharmacology
  • 1998
TLDR
Overall, CDS displays many characteristics expected of an endogenous regulator of insulin secretion acting through the islet beta-cell imidazoline site, which strengthens the hypothesis that the islets that were desensitized to the effects of the imdazoline secretagogue efaroxan were refractory to the actions of CDS.
Human alpha-endosulfine, a possible regulator of sulfonylurea-sensitive KATP channel: molecular cloning, expression and biological properties.
TLDR
It is proposed that endosulfine is an endogenous regulator of the KATP channel, which has a key role in the control of insulin release and, more generally, couples cell metabolism to electrical activity.
Evidence that the novel imidazoline compound FT005 is anα2‐adrenoceptor agonist
The aim of this study was to determine whether the hyperglycaemic action of the novel imidazoline compound FT005 could be mediated by activation of α2‐adrenoceptors, using a variety of in vivo and in
...
1
2
3
...

References

SHOWING 1-10 OF 27 REFERENCES
The imidazoline site involved in control of insulin secretion: characteristics that distinguish it from I1‐ and I2‐sites
TLDR
Results from down‐regulation experiments with isolated islets and from the radioligand binding studies suggest that the low affinity [3H]‐RX821002 binding site may represent the functional receptor responsible for the secretagogue activity of imidazoline compounds in the endocrine pancreas and that it has a pharmacological profile distinct from those of I1‐ and I2‐sites.
Effect of S-21663 (PMS 812), an imidazoline derivative, on glucose tolerance and insulin secretion in a rat model of type II diabetes.
TLDR
S-21663 can be considered as a potential hypoglycemic agent in Type II diabetes and chronic treatment (15 days) increased the efficiency.
Imidazolines stimulate release of insulin from RIN-5AH cells independently from imidazoline I1 and I2 receptors.
TLDR
The data indicate that the imidazoline/guanidine compounds promote insulin release from RIN-5AH cells, by interacting with a novel binding site related to K+ATP channels that does not represent any of the known imdazoline I1 or I2 receptors.
Increased cytosolic calcium. A signal for sulfonylurea-stimulated insulin release from beta cells.
TLDR
Findings provide direct experimental evidence that glyburide and tolbutamide allow extracellular Ca2+ to enter the beta cell through verapamil-sensitive, voltage-dependent Ca 2+ channels, causing a rise in [Ca2+]i which is the second messenger that stimulates insulin release.
Effect of secretagogues on cytosolic free Ca2+ and insulin release in the hamster clonal beta-cell line HIT-T15.
TLDR
The hypothesis that potentiators of insulin release which activate cAMP-dependent protein kinase orprotein kinase C do not increase Cai but sensitize the secretory mechanism to Ca2+ is supported.
Mobilization of Ca2+ from intracellular stores of pancreatic beta-cells by the calcium store blocker TMB-8.
TLDR
In pancreatic islets, TMB-8 appears to mobilize Ca2+ from intracellular stores, rather than inhibit the efflux as has been commonly accepted, which is a sufficient explanation for its potentiating effect on the rate of insulin secretion.
Effects of imidazolines and derivatives on insulin secretion and vascular resistance in perfused rat pancreas.
TLDR
Imidazolines and derivatives are able to stimulate insulin release and induce vasoconstriction in the rat pancreas and these effects cannot be ascribed to an interaction with alpha-adrenoceptors but may involve different types of imidazoline sites.
Phentolamine and yohimbine inhibit ATP‐sensitive K+ channels in mouse pancreatic β‐cells
TLDR
It is concluded that phentolamine inhibits ATP‐sensitive K+ channels in pancreatic β‐cells, which resembles that of hypoglycaemic sulphonylureas and may account for previously unexplained effects of the drug.
The receptor for antidiabetic sulfonylureas controls the activity of the ATP-modulated K+ channel in insulin-secreting cells.
TLDR
A 86Rb+ flux technique is described that permits one to study easily the properties of ATP-modulated K+ channels in RINm5F insulinoma cells and there was an excellent correlation between efficacy of blockade and efficacy of binding to the sulfonylurea receptors using the 3H-ligand.
The α2-adrenoceptor antagonist efaroxan modulates K+ATP channels in insulin-secreting cells
TLDR
Data indicate that efaroxan promotes insulin secretion, in the absence of exogenous agonists, by a mechanism that involves inhibition of ATP-regulated K + channels.
...
1
2
3
...