Inhibition of ATP-sensitive K+ channel by a non-sulfonylurea compound KAD-1229 in a pancreatic β-cell line, MIN 6 cell

Mogami, Hideo; Shibata, Hiroshi; Nobusawa, Romi; Ohnota, Hideki; Satou, Fumiyasu; Miyazaki, Jun‐ichi; Kojima, Itaru

doi:10.1016/0922-4106(94)90036-1

Cited by 35 publications

(20 citation statements)

References 8 publications

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“…This result is incongruent with a generally accepted mechanism in which mitiglinide acts solely through interaction with SUR1. Because mitiglinide's affinity for SUR1 has been shown to be weaker than glibenclamide's affinity for SUR, the more rapid fusion induced by mitiglinide is inexplicable in terms of binding affinity toward SUR1 (22). Furthermore, because the increase in [Ca 2ϩ ] i induced by mitiglinide and glibenclamide was almost similar, we cannot explain the faster fusion caused by mitiglinide in terms of [Ca 2ϩ ] i change.…”

Section: Discussionmentioning

confidence: 91%

“…Glinides such as mitiglinide lack the SUR moiety present on sulfonylureas, which facilitate these ligands binding to their cognate receptors (20,21). Nevertheless, mitiglinide was shown to inhibit [ 3 H]glibenclamide binding to SUR1 and caused increased [Ca 2ϩ ] i (22). Therefore, these drugs exhibit similar downstream effects but are structurally distinct and may use divergent mechanisms when compared with each other or with glucose.…”

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confidence: 99%

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Imaging Docking and Fusion of Insulin Granules Induced by Antidiabetes Agents

et al. 2006

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Sulfonylurea and glinide drugs, commonly used for antidiabetes therapies, are known to stimulate insulin release from pancreatic ␤-cells by closing ATP-sensitive K ؉ channels. However, the specific actions of these drugs on insulin granule motion are largely unknown. Here, we used total internal reflection fluorescence (TIRF) microscopy to analyze the docking and fusion of single insulin granules in live ␤-cells exposed to either the sulfonylurea drug glibenclamide or the glinide drug mitiglinide. TIRF images showed that both agents caused rapid fusion of newcomer insulin granules with the cell membrane in both control and diabetic Goto-Kakizaki (GK) rat pancreatic ␤-cells. However, in the context of ␤-cells from sulfonylurea receptor 1 (SUR1) knockout mice, TIRF images showed that only mitiglinide, but not glibenclamide, caused fusion of newcomer insulin granules. Compositely, our data indicate that 1) the mechanism by which both sulfonylurea and glinide drugs promote insulin release entails the preferential fusion of newcomer, rather than previously docked, insulin granules, and that 2) mitiglinide can induce insulin release by a mechanism independent of mitiglinide binding to SUR1.

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Section: Discussionmentioning

confidence: 91%

mentioning

confidence: 99%

Imaging Docking and Fusion of Insulin Granules Induced by Antidiabetes Agents

et al. 2006

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“…Summary statistics were calculated for efficacy and tive developed in Japan, which features rapid hypoglycemic action unlike SU agents [5][6][7]. It alleviates postprandial hyperglycemia and as a result improves glycemic control as a whole [8].…”

Section: Discussionmentioning

confidence: 99%

Effect of Mitiglinide on Glycemic Control over 52 Weeks in Japanese Type 2 Diabetic Patients Insufficiently Controlled with Pioglitazone Monotherapy

et al. 2009

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Abstract. This study was performed to examine the efficacy and safety of the rapid-and short-acting insulinotropic SUR ligand mitiglinide given as add-on therapy for 52 weeks in type 2 diabetic patients whose blood glucose was insufficiently controlled by pioglitazone monotherapy. Type 2 diabetic patients aged ≥20 years with postprandial plasma glucose (PPG1 or 2) ≥200 mg/dL and glycated hemoglobin (HbA 1C ) 6.5-<9.0% despite receiving pioglitazone 15-45 mg/day were additionally treated with concomitant mitiglinide 10 mg tid p.o. for a total treatment period of 52 weeks. In 171 patients recruited, HbA1C was significantly reduced from 7.64 ± 0.77% at baseline to 6.84 ± 0.73%, 6.64 ± 0.64%, 6.67 ± 0.57% and 6.81 ± 0.65% at weeks 16, 28, 40, and 52, respectively. Over half the patients achieved HbA 1C target of <7.0%, and one third <6.5%. Significant reductions in fasting plasma glucose (FPG) and PPG 1 and 2 hours after a meal versus baseline were noted at all time-points evaluated. The most frequently noted adverse reactions were hypoglycemic symptoms, weight gain, and peripheral edema (all mild). In type 2 diabetic patients combination therapy with mitiglinide and pioglitazone exerted significant long-term improvements in HbA 1C , FPG, and PPG and was well tolerated. This drug combination therapy is a promising means of alleviating insufficient pancreatic insulin secretion and insulin resistance. TYPE 2 diabetes mellitus is a syndrome involving insufficient insulin secretion from pancreatic β-cells and insulin resistance in peripheral tissues [1]. Patients with this disease often have postprandial hyperglycemia because rapid additional secretion of insulin after meals is insufficient, and a vicious circle of glucotoxicity leading to protracted and advanced hyperglycemia arises when this condition continues. It has become clear from large-scale clinical studies that postprandial hyperglycemia is a risk factor for arteriosclerosis independent of hypertension and hyperlipidemia [2,3]. In the STOP-NIDDM trial [4] it was shown that improvement in postprandial hyperglycemia exerted by α-glucosidase inhibitors in patients with impaired glucose tolerance (IGT) delays the onset of cardiovascular events, and the importance of correction of postprandial hyperglycemia on limiting the progression of diabetes as well as preventing the onset of macrovascular diseases was thus suggested.At present, sulfonylurea (SU) agents and rapid-and short-acting insulinotropic SU receptor (SUR) ligands are used to supplement insufficient insulin secretion in type 2 diabetic patients. SU agents have strong hypoglycemic actions, but are ineffective at promoting additional secretion of insulin after meals. In addition, these agents are known to induce protracted hypoglycemia and obesity is a problem associated with their use. Mitiglinide is a new rapid-and short-acting insulinotropic SUR ligand, a benzylsuccinic acid deriva- Study designThis was an open label study that consisted of a pretreatment observation period lasting 4 weeks and a 52-we...

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“…The profile of mitiglinide (KAD-1229), a third meglitinide analog and derivative of benzylsuccinic acid (Bakkali-Nadi et al, 1994a,b;Mogami et al, 1994;Ohnota et al, 1994) is not much different from the already known rapid-acting glinides (reviewed by Malaisse, 2008): plasma concentrations (maximum after approximately 20 min), linear pharmacokinetics, metabolism, uptake by pancreatic islets, insulinotropic action, effect on ionic channels, glucose uptake by hepatocytes (note that there is a possible advantage of this extrapancreatic effect), preclinical investigations, and cardiovascular effects (possibly weaker than those of glibenclamide or glimepiride). Its receptor binding was unaffected by 100 M glibenclamide (glyburide) (Malaisse, 2008), indicating no cross-reaction with their binding sites.…”

Section: New Glinidesmentioning

confidence: 99%

Novel Pharmacological Approaches to the Treatment of Type 2 Diabetes

Verspohl

2012

Pharmacol Rev

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Inhibition of ATP-sensitive K+ channel by a non-sulfonylurea compound KAD-1229 in a pancreatic β-cell line, MIN 6 cell

Cited by 35 publications

References 8 publications

Imaging Docking and Fusion of Insulin Granules Induced by Antidiabetes Agents

Imaging Docking and Fusion of Insulin Granules Induced by Antidiabetes Agents

Effect of Mitiglinide on Glycemic Control over 52 Weeks in Japanese Type 2 Diabetic Patients Insufficiently Controlled with Pioglitazone Monotherapy

Novel Pharmacological Approaches to the Treatment of Type 2 Diabetes

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