Stimulation of insulin release by benzoic acid derivatives related to the non-sulphonylurea moiety of glibenclamide: Structural requirements and cellular mechanisms

Henquin, Jean‐Claude; Garrino, Maria-Grazia; Nenquin, Myriam

doi:10.1016/0014-2999(87)90269-x

Cited by 29 publications

(13 citation statements)

References 17 publications

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“…Considering the early stress on, and historic observations of, the importance of the sulfonamide or sulfonylurea moiety, the finding that non-sulfonylurea benzoic acid derivatives were active hypoglycemic compounds was a surprise. Several studies compared the effectiveness of compounds with, versus without, the sulfonylurea group on K ATP channels [151][152][153][154]. A discussion (e.g., [148,152]) over the issue of how two sites within the same receptor could both effect increased insulin secretion ensued with Henquin et al [152] concluding that "K channels appear to possess, not a sulphonylurea receptor, but a target site for various chemical groups".…”

Section: Structure Activity Relations Of 2 Nd Gene-ration Hypoglycemimentioning

confidence: 98%

“…Several studies compared the effectiveness of compounds with, versus without, the sulfonylurea group on K ATP channels [151][152][153][154]. A discussion (e.g., [148,152]) over the issue of how two sites within the same receptor could both effect increased insulin secretion ensued with Henquin et al [152] concluding that "K channels appear to possess, not a sulphonylurea receptor, but a target site for various chemical groups". This discussion continues to the present with studies on nateglinide and the meglitinide analog, repaglinide (see for example [155]).…”

Section: Structure Activity Relations Of 2 Nd Gene-ration Hypoglycemimentioning

confidence: 98%

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Insulin Secretagogues, Sulfonylurea Receptors and KATP Channels

Bryan¹,

Crane²,

Vila-Carriles³

et al. 2005

CPD

116

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ATP-sensitive K+ channels, termed K(ATP) channels, provide a link between cellular metabolism and membrane electrical activity in a variety of tissues. Channel isoforms have been identified and are targets for compounds that both stimulate and inhibit their activity resulting in membrane hyperpolarization and depolarization, respectively. Examples include relaxation of vascular smooth muscle and stimulation of insulin secretion. This article reviews the cloning, molecular biology, and structure of K(ATP) channels, with particular focus on the SUR1/K(IR)6.2 neuroendocrine channels that are important for the regulation of insulin secretion. We integrate the extensive pharmacologic structure-activity-relationship data on these channels, which defines a bipartite drug binding pocket in the SUR (sulfonylurea receptor), with recent structure-function studies that identify domains of SUR and K(IR)6.2, the channel pore, which are critical for channel assembly, for gating, and for the ligand-receptor interactions that modulate channel activity. The atomic structure of a sulfonylurea in a protein pocket is used to develop insight into the recognition of these compounds. A homology model of K(ATP) channels, based on VC-MsbA, another member of the ABC protein family, is described and used to position amino acids important for the action of channel openers and blockers within the core of SUR. The model has a central chamber which could serve as a multifaceted binding pocket.

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Section: Structure Activity Relations Of 2 Nd Gene-ration Hypoglycemimentioning

confidence: 98%

Section: Structure Activity Relations Of 2 Nd Gene-ration Hypoglycemimentioning

confidence: 98%

Insulin Secretagogues, Sulfonylurea Receptors and KATP Channels

Bryan¹,

Crane²,

Vila-Carriles³

et al. 2005

CPD

116

View full text Add to dashboard Cite

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“…Its derivatization with a cyclohexyl moiety resulted in elevated lipophilicity (region E), which is probably responsible for high plasma protein binding as well as effective membrane and cell penetration (Schwanstecher et al, 1994). Interestingly, the benzamido group alone is also likely to interact with SUR1, since a benzoic acid derivative of glibenclamide and meglitinide (Table 1) has been shown to induce insulin release (Henquin et al, 1987). Thus it seems plausible that the concerted interaction with the meglitinide-and tolbutamide-binding sites probably accounts for the several thousand-fold increase in affinity of glibenclamide equipped with both a benzamido (5-chloro-N-ethylen-2-methoxy benzamide) (Figures 1 and 3, region C) and a sulphonylurea moiety (region D) vs. tolbutamide equipped with a sulphonylurea moiety, only (Figure 1; Schwanstecher et al, 1998;Ashfield et al, 1999).…”

Section: Discussionmentioning

confidence: 96%

Novel glimepiride derivatives with potential as double-edged swords against type II diabetes

Müller¹,

Schulz

Hartz

et al. 2010

Archives of Physiology and Biochemistry

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“…Thus, repaglinide is appropriately considered a meglitinide analogue [8]. Meglitinide is known to produce SU-like activity in vitro [9] and in vivo [10] by blocking K ATP channels in pancreatic beta cells [11]. The hypoglycaemic activity of repaglinide resides predominantly in the S-enantiomer, in which the acidic (COOH) and amidic (CONH) groups are supposedly involved in binding to two putative sites of the SUR [12].…”

Section: Introductionmentioning

confidence: 99%

The mechanisms underlying the unique pharmacodynamics of nateglinide

Boettcher

Dunning

2003

Diabetologia

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Nateglinide, a D-phenylalanine derivative, belongs to a new group of insulinotropic agents with rapid onset and short duration of action. These agents have been developed to reduce the risk of hypoglycaemia associated with pharmacological control and to decrease the likelihood of pancreatic beta-cell exhaustion. Nateglinide mediates the release of insulin from beta-cells by binding to the sulphonylurea receptors, which leads to the closure of ATP-sensitive K + channels. Increasing evidence from receptor binding, mechanistic and in vitro and in vivo insulin studies indicate unique pharmacodynamic and pharmacokinetic properties with nateglinide that are distinct from those of sulphonylureas. The time required by nateglinide to close beta-cell K ATP channels is comparable to that of glyburide but threefold and fivefold faster than repaglinide and glimepiride, respectively. Furthermore, its effects are rapidly reversed with an off-rate at the K ATP channel twice as fast as that of glyburide and glimepiride and five times faster than repaglinide. This results in a rapid and short insulin response characteristic of the physiological pattern of post-mealtime insulin release. Internalisation into beta-cells is not required for the action of nateglinide. Given that the kinetic profile of the agent is associated with selective enhancement of early-phase insulin secretion, nateglinide is expected to minimise post-meal hyperglycaemia with minimal propensity for hypoglycaemia. [Diabetologia (2003)

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Stimulation of insulin release by benzoic acid derivatives related to the non-sulphonylurea moiety of glibenclamide: Structural requirements and cellular mechanisms

Cited by 29 publications

References 17 publications

Insulin Secretagogues, Sulfonylurea Receptors and KATP Channels

Insulin Secretagogues, Sulfonylurea Receptors and KATP Channels

Novel glimepiride derivatives with potential as double-edged swords against type II diabetes

The mechanisms underlying the unique pharmacodynamics of nateglinide

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