Sulfonylurea Stimulation of Insulin Secretion

Proks, Peter; Reimann, Frank; Green, Nick; Gribble, Fiona M.; Ashcroft, Frances M.

doi:10.2337/diabetes.51.2007.s368

Cited by 430 publications

(325 citation statements)

References 54 publications

(54 reference statements)

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“…Accordingly, the remaining part of the LA-induced stimulatory effect completely disappeared when the islets were challenged for 30 min with LA prior to the 48-hour antisense exposure period. The fact that a tolbutamide-induced insulin release (Proks et al 2002) was unaffected by both antisense oligonucleotide and LA indicates that the suppressive effect was specific.…”

Section: Discussionmentioning

confidence: 96%

Free fatty acid receptor 1 (FFA1R/GPR40) and its involvement in fatty-acid-stimulated insulin secretion

Salehi¹,

et al. 2005

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Section: Discussionmentioning

confidence: 96%

Free fatty acid receptor 1 (FFA1R/GPR40) and its involvement in fatty-acid-stimulated insulin secretion

Salehi¹,

et al. 2005

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“…Their hypoglycaemic action is attributed to a stimulation of insulin release that rapidly follows the drug's binding to a surface membrane receptor and a subsequent rise in cytoplasmic free calcium concentration [28,29]. We recently reported that glibenclamide, a second-generation sulfonylurea, also exerts a stimulatory effect on insulin synthesis when present over a prolonged period, i.e.…”

Section: Discussionmentioning

confidence: 99%

Glibenclamide activates translation in rat pancreatic beta cells through calcium-dependent mTOR, PKA and MEK signalling pathways

et al. 2008

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Aims/hypothesis Prolonged exposure of rat beta cells to the insulin secretagogue glibenclamide has been found to induce a sustained increase in basal insulin synthesis. This effect was calcium-dependent and localised in cells that had been degranulated by the drug. Since it was blocked by the translation inhibitor cycloheximide, we examined whether sustained exposure to glibenclamide activates translational factors by calcium-dependent signalling pathways. Methods Purified rat beta cells were cultured with and without glibenclamide in the presence or absence of inhibitors of calcium-dependent signalling pathways before measurement of basal and stimulated protein and insulin synthesis, and assessment of abundance of (phosphorylated) translation factors.Results A 24 h exposure to glibenclamide induced activation of four translation factors, i.e. phosphorylation of eukaryotic initiation factor (eIF) 4e binding protein 1 and ribosomal protein S6 (rpS6), and dephosphorylation of eIF-2α and eukaryotic elongation factor 2. The rise in phospho-rpS6 intensity was localised to a subpopulation of beta cells with low insulin content. This activation of translational factors and the associated elevation of insulin synthesis were completely blocked by the calcium channel blocker verapamil and partially blocked by the mammalian target of rapamycin (mTOR) inhibitor rapamycin, the protein kinase A (PKA) inhibitor Rp-8-Br-cAMPs and the mitogen-activated protein kinase/ extracellular signal-regulated kinase kinase (MEK) inhibitor U0126; a combination of inhibitors exhibited additive effects. Conclusions/interpretation Prolonged exposure to glibenclamide activates protein translation in pancreatic beta cells through the calcium-regulated mTOR, PKA and MEK signalling pathways. The observed intercellular differences in translation activation are proposed as underlying mechanism for functional heterogeneity in the pancreatic beta cell population.

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“…[14][15][16] ). We used constant infusion of a low dose of drug to achieve sustained occupancy of only high-affinity receptors.…”

Section: Glibenclamide Treatment In Mce Modelmentioning

confidence: 99%

Newly expressed SUR1-regulated NCCa-ATP channel mediates cerebral edema after ischemic stroke

Simard

Chen

Tarasov

et al. 2006

Nat Med

391

523

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Pathological conditions in the central nervous system, including stroke and trauma, are often exacerbated by cerebral edema. We recently identified a nonselective cation channel, the NC Ca-ATP channel, in ischemic astrocytes that is regulated by sulfonylurea receptor 1 (SUR1), is opened by depletion of ATP and, when opened, causes cytotoxic edema. Here, we evaluated involvement of this channel in rodent models of stroke. SUR1 protein and mRNA were newly expressed in ischemic neurons, astrocytes and capillaries. Upregulation of SUR1 was linked to activation of the transcription factor Sp1 and was associated with expression of functional NC Ca-ATP but not K ATP channels. Block of SUR1 with low-dose glibenclamide reduced cerebral edema, infarct volume and mortality by 50%, with the reduction in infarct volume being associated with cortical sparing. Our findings indicate that the NC Ca-ATP channel is crucially involved in development of cerebral edema, and that targeting SUR1 may provide a new therapeutic approach to stroke.Edema complicates many conditions that affect the central nervous system (CNS), including stroke and trauma. Edema worsens neurological function and can threaten life. Swelling resulting from malignant cerebral edema after a large middle cerebral artery (MCA) stroke is responsible for the high mortality of 60−80% of the patients 1 . Molecular mechanisms of cerebral edema are poorly understood, and available treatments are nonspecific and only moderately effective 1 .SUR1 is a regulatory subunit that associates with Kir6.x pore-forming subunits to form heterooctameric K ATP channels 2 . SUR1 confers sensitivity to sulfonylurea inhibitors such as glibenclamide and to channel activators such as diazoxide. Apart from involvement with

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Sulfonylurea Stimulation of Insulin Secretion

Cited by 430 publications

References 54 publications

Free fatty acid receptor 1 (FFA1R/GPR40) and its involvement in fatty-acid-stimulated insulin secretion

Free fatty acid receptor 1 (FFA1R/GPR40) and its involvement in fatty-acid-stimulated insulin secretion

Glibenclamide activates translation in rat pancreatic beta cells through calcium-dependent mTOR, PKA and MEK signalling pathways

Newly expressed SUR1-regulated NCCa-ATP channel mediates cerebral edema after ischemic stroke

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