Effect of the Meglitinide Analog S214o3 on Cationic Fluxes and Insulin Release in Perifused Rat Pancreatic Islets Exposed to a High Concentration of D-Glucose

Louchami, Karim; Jijakli, Hassan; Malaisse, Willy

doi:10.1006/phrs.1999.0513

Cited by 3 publications

(1 citation statement)

References 13 publications

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“…Mitiglinide is the newest drug in the meglitinide family 8 . It also has a rapid mode of action 9,10 and shows a higher selectivity for pancreatic β cells than other meglitinides, including nateglinide and repaglinide, through a high affinity to SUR1, a subunit of the K ATP in pancreatic β cells 11,12 . In addition, its calcium ionophoretic activity, which results in the stimulation of calcium influx and subsequent insulin secretion 9,10 , is greater than that of nateglinide and repaglinide 13 .…”

Section: Introductionmentioning

confidence: 99%

Effect of the combination of mitiglinide and metformin on glycemic control in patients with type 2 diabetes mellitus

Cho

Koo

Son

et al. 2010

J of Diabetes Invest

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Aims/Introduction: Mitiglinide is the newest drug in the meglitinide family. It increases the early‐phase insulin release through rapid association‐dissociation kinetics in the pancreatic β cells. The efficacy and safety of adding meglitinide to metformin monotherapy in patients with type 2 diabetes are unknown.Materials and Methods: We carried out a prospective, randomized, multicenter trial to assess the efficacy and safety of combined treatment with mitiglinide and metformin for patients with type 2 diabetes who showed inadequate glycemic control with metformin monotherapy. Subjects with glycated hemoglobin (HbA1c) >7.0% after an 8‐week metformin run‐in phase were randomized to a 16‐week trial phase with metformin plus mitiglinide (Met + Mit) or metformin plus placebo (Met + Pcb).Results: Compared with the Met + Pcb group, the Met + Mit group showed a greater reduction in HbA1c (−0.7 ± 0.6%vs−0.4 ± 0.7%, P = 0.002), fasting plasma glucose (−0.77 ± 1.76 mmol/L vs−0.05 ± 1.60 mmol/L, P = 0.015) and 2‐h postprandial glucose (−3.76 ± 3.57 mmol/L vs−0.84 ± 3.07 mmol/L, P < 0.0001). The proportion of the patients who achieved the target HbA1c value of <7% at the end of the study was also higher in the Met + Mit group than the Met + Pcb group (49.3%vs 28.8%, P = 0.016). There were no differences in the adverse event rates between groups.Conclusions: Combination therapy with metformin and mitiglinide is effective and safe for the treatment of patients with type 2 diabetes who have inadequate glycemic control with metformin monotherapy. (J Diabetes Invest, doi: 10.1111/j.2040‐1124.2010.00023.x, 2010)

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Section: Introductionmentioning

confidence: 99%

Effect of the combination of mitiglinide and metformin on glycemic control in patients with type 2 diabetes mellitus

Cho

Koo

Son

et al. 2010

J of Diabetes Invest

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Mitiglinide: a rapid- and short-acting non-sulfonylurea insulinotropic agent for the treatment of type 2 diabetic patients

Malaisse

2008

Expert Opinion on Pharmacotherapy

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Pharmacology of the Meglitinide Analogs

Malaisse¹

2003

Treatments in Endocrinology

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The expression meglitinide analogs was introduced in 1995 to cover new molecules proposed as non-sulfonylurea insulinotropic agents and displaying structural analogy with meglitinide, such as repaglinide, nateglinide, and mitiglinide. Meglitinide analogs display, as judged by conformation analysis, a U-shaped configuration similar to that of antihyperglycemic sulfonylureas such as glibenclamide (glyburide) and glimepiride. In rat pancreatic islets incubated in the presence of 7.0 mmol/L D-glucose, repaglinide and mitiglinide demonstrate comparable concentration-response relationships for stimulation of insulin release, with a threshold value < 10 nmol/L and a maximal secretory response at about 10 nmol/L. Several findings indicate that meglitinide analogs provoke the closing of adenosine triphosphate-sensitive potassium channels, with subsequent gating of voltage-sensitive calcium channels. The effects of meglitinide analogs upon the binding of [3H]glibenclamide to islet cells membranes reinforces this concept. At variance, however, with other meglitinide analogs, the ionic and secretory response to repaglinide (10 micromol/L) is not rapidly reversible in perifused rat islets. In experiments conducted in vivo in control and diabetic rats, repaglinide provokes a greater and more rapid increase in plasma insulin concentration and an earlier fall in glycemia than glibenclamide or glimepiride. Onset of effect is also more rapid and duration of effect shorter with nateglinide versus glibenclamide. In clinical studies, single or repeated daily administration of repaglinide increased plasma insulin concentration in a dose-dependent manner, with an incremental peak reached about 2 hours after repaglinide intake. Plasma concentrations of repaglinide are about 5.0 microg/L 2-2.5 hours after oral intake of the drug. Despite the slow reversibility of repaglinide action in vitro, this drug offers advantages over glibenclamide in terms of the possible occurrence of hypoglycemia if a meal is missed. In volunteers receiving a single oral dose of nateglinide (120mg) 10 minutes before a standardized 800 Kcal breakfast, the plasma insulin concentration was higher 5, 10, and 20 minutes after meal intake than when they received a single dose of repaglinide (0.5 or 2.0mg) or placebo 10 minutes before breakfast. Peak plasma concentrations of nateglinide were reached within 2 hours in most volunteers. Peak plasma concentrations of mitiglinide were reached 30 minutes after a single oral dose in a representative volunteer. Mitiglinide significantly suppressed meal-induced elevations in blood glucose concentrations in a study of patients with type 2 diabetes. In conclusion, two obvious differences among these meglitinide analogs should be underlined. First, on a molar basis, nateglinide is somewhat less potent than repaglinide or mitiglinide, as an insulinotropic agent. The maximal secretory responses evoked by these three meglitinide analogs are, however, identical to one another. Secondly, and as already mentioned, the functional effects...

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Effect of the Meglitinide Analog S214o3 on Cationic Fluxes and Insulin Release in Perifused Rat Pancreatic Islets Exposed to a High Concentration of D-Glucose

Cited by 3 publications

References 13 publications

Effect of the combination of mitiglinide and metformin on glycemic control in patients with type 2 diabetes mellitus

Effect of the combination of mitiglinide and metformin on glycemic control in patients with type 2 diabetes mellitus

Mitiglinide: a rapid- and short-acting non-sulfonylurea insulinotropic agent for the treatment of type 2 diabetic patients

Pharmacology of the Meglitinide Analogs

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