Potassium selective ion channels in insulin-secreting cells: physiology, pharmacology and their role in stimulus-secretion coupling

Dunne, M. J.; Petersen, O. H.

doi:10.1016/0304-4157(91)90012-l

Cited by 156 publications

(97 citation statements)

References 134 publications

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“…hypoglycaemia without affecting TNF production or parasitaemia. Diazoxide opens ATP-sensitive K channels [33], hyperpolarizes pancreatic -cells, and thereby inhibits the secretion of insulin and induces hyperglycaemia [34]. These findings agree with our earlier observations that the MoAb to TNF did not inhibit the drop in blood glucose induced by malaria toxin [13], but that diazoxide did [12]; they also support the view that parasite molecules can induce hypoglycaemia directly by stimulating secretion of insulin, rather than through the production of TNF.…”

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confidence: 91%

Malaria, blood glucose, and the role of tumour necrosis factor (TNF) in mice

Elased

Taverne

Playfair

1996

Clinical and Experimental Immunology

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SUMMARYHypoglycaemia in falciparum malaria is associated with a poor prognosis and is correlated with mortality. High levels of serum TNF are also correlated with disease severity and mortality, and it has been suggested that TNF may cause the hypoglycaemia. However hypoglycaemia in mice infected with Plasmodium chabaudi or the lethal strain of P. yoelii YM is related to hyperinsulinaemia. Its development was not prevented by treatments which diminished TNF activity or production without affecting levels of plasma insulin. Conversely, it was inhibited by diazoxide, which inhibited insulin secretion but did not affect TNF production. Furthermore, in mice exhibiting neurological symptoms during infection with P. berghei, blood glucose concentrations were significantly raised when TNF levels were high, and TNF levels in the spleen were highest of all in non-lethal P. yoelii infections in which hypoglycaemia does not occur. Administration of human rTNF to normal animals caused an increase rather than a drop in blood glucose levels. Mice transgenic for human TNF did not develop hypoglycaemia when infected with P. yoelii YM, but showed signs of insulin resistance. In line with current views on the role of TNF in obesity and the control of glucose homeostasis, we conclude that the hypoglycaemia of malaria is not caused by increased levels of TNF, which may in fact be beneficial, but is secondary to a hyperinsulinaemia that is probably stimulated directly by products of the parasite.

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confidence: 91%

Malaria, blood glucose, and the role of tumour necrosis factor (TNF) in mice

Elased

Taverne

Playfair

1996

Clinical and Experimental Immunology

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“…The resting potential maintained across the plasma membrane of the pancreatic P-cell is determined primarily by a large efflux of potassium ions (Ozawa & Sand, 1986;Henquin, 1987;Dunne & Petersen, 1991;Ashcroft et al, 1992;Boyd, 1992). This efflux is facilitated by a range of potassium channels in the P-ell plasma membrane, which remain open in the resting state.…”

Section: Introductionmentioning

confidence: 99%

“…This efflux is facilitated by a range of potassium channels in the P-ell plasma membrane, which remain open in the resting state. The most important of these is a channel the open state of which varies according to the ATP/ADP ratio within the cell (the K-ATP channel ;Cook et al, 1988;Dunne & Petersen, 1991;Ashcroft et al, 1992;Boyd, 1992).…”

Section: Introductionmentioning

confidence: 99%

Antagonism of the stimulatory effects of efaroxan and glibenclamide in rat pancreatic islets by the imidazoline, RX801080

Brown

Chan

Stillings³

et al. 1993

British J Pharmacology

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1 The imidazoline M2-adrenoceptor antagonist, efaroxan, stimulates insulin secretion from rat isolated islets and antagonizes the ability of diazoxide to inhibit glucose-induced insulin secretion. These effects result from closure of ATP-sensitive potassium channels although the mechanisms involved have not been elucidated. 2 In the present work, we have examined the effects of a close structural analogue of efaroxan, RX801080, in rat isolated islets of Langerhans. RX801080 was found to be ineffective as a stimulator of insulin secretion and did not prevent the inhibition of insulin secretion mediated by diazoxide. 3 RX801080 acted as an antagonist of the actions of several imidazolines (efaroxan, phentolamine and midaglizole) in rat islets. It dose-dependently inhibited the ability of efaroxan to antagonize the effects of diazoxide in islets and also completely inhibited the direct stimulation of insulin secretion mediated by efaroxan. 4 RX801080 also antagonized the effects of the non-imidazoline, ATP-sensitive potassium channel blocker, glibenclamide, in rat islets. It inhibited both the capacity of glibenclamide to stimulate insulin secretion and the ability of glibenclamide to overcome the inhibitory effects of diazoxide in rat islets. 5 Antagonism of glibenclamide responses by RX801080 was not due to inhibition of binding of the sulphonylurea to its receptor on the pancreatic P-cell. 6 The results suggest that imidazoline compounds and sulphonylureas interact with distinct binding sites on islet cells, but that these sites can interact functionally to control islet cell ATP-sensitive potassium channel activity and insulin secretion.

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“…Interaction of insulinotropic ligands with the membrane SUR1 protein results in the closure of the K ATP channel, membrane depolarisation and entry of extracellular calcium via the voltage-gated (L-Type) Ca ++ channel. The increased intracellular free Ca ++ concentration acts as a stimulus for exocytosis of insulin-containing secretory granules [6,7].…”

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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Potassium selective ion channels in insulin-secreting cells: physiology, pharmacology and their role in stimulus-secretion coupling

Cited by 156 publications

References 134 publications

Malaria, blood glucose, and the role of tumour necrosis factor (TNF) in mice

Malaria, blood glucose, and the role of tumour necrosis factor (TNF) in mice

Antagonism of the stimulatory effects of efaroxan and glibenclamide in rat pancreatic islets by the imidazoline, RX801080

The mechanisms underlying the unique pharmacodynamics of nateglinide

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