(R)-ACX is a novel sufonylurea compound with potent, quick and short-lasting hypoglycemic activity

Seri, Kenji; Sanai, Kazuko; Kurashima, Katsumi; Imamura, Yorishige; Akita, Hiroyuki

doi:10.1016/s0014-2999(99)00922-x

Cited by 19 publications

(8 citation statements)

References 8 publications

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“…Sulfonylureas and non-sulfonylurea analogs R-acetohexamide is a new sulfonylurea with a more rapid onset of action and a shorter duration of hypoglycemic activity than glibenclamide [20]; its short duration of action may help to control post-prandial hyperglycemia with a low risk of hypoglycemia.…”

Section: Novel K Atp Channel Modulatorsmentioning

confidence: 99%

Pharmacological interventions that directly stimulate or modulate insulin secretion from pancreatic β‐cell: implications for the treatment of type 2 diabetes

Farret

Lugo-Garcia

Galtier

et al. 2005

Fundamemntal Clinical Pharma

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Blood glucose concentration is controlled by a number of hormone and neurotransmitter signals, either increasing or reducing glucose levels in the case of hypoglycemia or hyperglycemia, respectively. The pancreatic beta-cell responds to an increase in circulating glucose levels by a cascade of metabolic and electrophysiological events leading to the secretion of insulin. Type 2 diabetes is a metabolic disorder characterized by chronic hyperglycemia; the progressive pancreatic beta-cell dysfunction, with altered insulin production and secretion, is a major pathophysiological determinant of the disease together with the resistance of insulin-sensitive tissues to the action of the hormone. Hence, drugs which stimulate or enhance insulin secretion will reduce plasma glucose concentrations; this lowering of hyperglycemia will, in turn, reduce the occurrence of long-term complications. K(ATP) channels play a critical role in insulin secretion and can be considered as transducers of glucose-induced metabolic changes into biophysical events leading to the exocytosis of insulin granules. All currently marketed insulin secretagogues, sulfonylureas and glinides, target the beta-cell K(ATP) channels and reduce their opening probability. They induce insulin release regardless of the plasma glucose concentration, thus favoring the occurrence of hypoglycemia in the fasting state. Despite the intensive use of current drugs, many patients suffering from type 2 diabetes still exhibit poor glycemic control, others fail to respond to the treatment, and some develop serious complications. Therefore, there is a real need for innovative compounds, either enhancing insulin secretion from the pancreas or improving insulin action on the hormone-sensitive tissues. Here, we overview the existing and novel approaches targeting the beta-cell to enhance the release of insulin, with special emphasis on new ways of amplifying insulin secretion in a glucose-dependent manner.

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Section: Novel K Atp Channel Modulatorsmentioning

confidence: 99%

Pharmacological interventions that directly stimulate or modulate insulin secretion from pancreatic β‐cell: implications for the treatment of type 2 diabetes

Farret

Lugo-Garcia

Galtier

et al. 2005

Fundamemntal Clinical Pharma

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“…Micromolar concentrations of the K ATP channel antagonist glyburide (Sigma, St. Louis, MO) have been shown to stimulate insulin secretion from HIT-T15 cells in the absence of glucose (32,33). Micromolar concentrations of the K ATP channel antagonist glyburide (Sigma, St. Louis, MO) have been shown to stimulate insulin secretion from HIT-T15 cells in the absence of glucose (32,33).…”

Section: Effect Of I Dr Inhibition On Insulin Secretionmentioning

confidence: 99%

Members of the Kv1 and Kv2 Voltage-Dependent K+ Channel Families Regulate Insulin Secretion

MacDonald

Wang

et al. 2001

Molecular Endocrinology

159

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In pancreatic beta-cells, voltage-dependent K(+) (Kv) channels are potential mediators of repolarization, closure of Ca(2+) channels, and limitation of insulin secretion. The specific Kv channels expressed in beta-cells and their contribution to the delayed rectifier current and regulation of insulin secretion in these cells are unclear. High-level protein expression and mRNA transcripts for Kv1.4, 1.6, and 2.1 were detected in rat islets and insulinoma cells. Inhibition of these channels with tetraethylammonium decreased I(DR) by approximately 85% and enhanced glucose-stimulated insulin secretion by 2- to 4-fold. Adenovirus-mediated expression of a C-terminal truncated Kv2.1 subunit, specifically eliminating Kv2 family currents, reduced delayed rectifier currents in these cells by 60-70% and enhanced glucose-stimulated insulin secretion from rat islets by 60%. Expression of a C-terminal truncated Kv1.4 subunit, abolishing Kv1 channel family currents, reduced delayed rectifier currents by approximately 25% and enhanced glucose-stimulated insulin secretion from rat islets by 40%. This study establishes that Kv2 and 1 channel homologs mediate the majority of repolarizing delayed rectifier current in rat beta-cells and that antagonism of Kv2.1 may prove to be a novel glucose-dependent therapeutic treatment for type 2 diabetes.

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“…Several sulfonamide derivatives have been used as chemotherapeutic agents for their antibacterial, antifungal, antitumor and hypoglycemic effects for many years, see: Chohan et al (2010); El-Sayed et al (2011); Seri et al (2000). Some sulfonamide derivatives are reported to have carbonic anhydrases (CA) inhibition properties, see: Suparan et al (2000).…”

Section: Related Literaturementioning

confidence: 99%

N-[2-(9H-Carbazol-9-yl)ethyl]-4-(methylsulfonyl)aniline

Lai

Gallucci

2014

Acta Cryst E

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(R)-ACX is a novel sufonylurea compound with potent, quick and short-lasting hypoglycemic activity

Cited by 19 publications

References 8 publications

Pharmacological interventions that directly stimulate or modulate insulin secretion from pancreatic β‐cell: implications for the treatment of type 2 diabetes

Pharmacological interventions that directly stimulate or modulate insulin secretion from pancreatic β‐cell: implications for the treatment of type 2 diabetes

Members of the Kv1 and Kv2 Voltage-Dependent K+ Channel Families Regulate Insulin Secretion

N-[2-(9H-Carbazol-9-yl)ethyl]-4-(methylsulfonyl)aniline

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