Insulinotropic action of meglitinide analogues: modulation by an activator of ATP-sensitive K+ channels and high extracellular K+ concentrations.

@article{Malaisse1995InsulinotropicAO,
  title={Insulinotropic action of meglitinide analogues: modulation by an activator of ATP-sensitive K+ channels and high extracellular K+ concentrations.},
  author={Willy J Malaisse},
  journal={Pharmacological research},
  year={1995},
  volume={32 3},
  pages={
          111-4
        }
}
  • W. Malaisse
  • Published 1995
  • Biology, Medicine
  • Pharmacological research
At normal extracellular K+ concentration (5 mM), the meglitinide analogues A-4166, KAD-1229, repaglinide and S3075, all tested at a 10 mu M concentration, markedly enhanced insulin release evoked by 6 mM D-glucose in isolated rat pancreatic islets. They failed, however, to augment the much higher rate of insulin release evoked by D-glucose in islets exposed to a high K+ concentration (30 mM). Under the latter conditions, the potent diazoxide analogue BPDZ-44 (50 mu M) did not exert any sizeable… Expand
Pathways in beta-cell stimulus-secretion coupling as targets for therapeutic insulin secretagogues.
TLDR
This review identifies six major pathways or sites of stimulus-secretion coupling that could be aimed by potential insulin-secreting drugs and describes several strategies to reach these targets and discusses whether these perspectives are realistic or theoretical only. Expand
Pharmacology of the Meglitinide Analogs
TLDR
The expression meglitinide analogs offer the advantage over the long-acting antihyperglycemic sulfonylurea glibenclamide of minimizing the risk of undesirable hypoglycemia, and on a molar basis, nateglinide is somewhat less potent than repaglinide or mitiglinide, as an insulinotropic agent. Expand
Repaglinide, a new oral antidiabetic agent: a review of recent preclinical studies
  • Malaisse
  • Medicine
  • European journal of clinical investigation
  • 1999
TLDR
Repaglinide is a new carbamoylmethyl benzoic acid derivative that is structurally related to meglitinide that causes a more rapid increase in plasma insulin levels in rats than either glibenclamide or glimepiride. Expand
Analogues du méglitinide : nouveaux agents insulinotropes pour le traitement du diabète non-insulinodépendant Meglitinide analogs : new insulinotropic agents for the treatment of non-insulindependent diabetes mellitus
TLDR
The present report aims at reviewing both preclinical studies and clinical investigations concerning the latter three meglitinide analogs, which differ from one another by their potency as insulinotropic agents and by the time course of their biological effects, especially in terms of the reversibility of such effects. Expand
Long-term effects of glibenclamide and nateglinide upon pancreatic islet function in normal and diabetic rats.
TLDR
It is proposed that the meglitinide analog, considered as a new insulinotropic tool for the treatment of non-insulin-dependent diabetic subjects, may offer the far-from-negligible advantage of minimising the risk of a sustained decrease in both islet insulin content and glycaemia. Expand
Evidence for a KATP Channel in Rough Endoplasmic Reticulum (rerKATP Channel) of Rat Hepatocytes
TLDR
It was concluded on the basis of these observations that the channel previously characterized in RER membranes corresponds to KATP, suggesting that opening of this channel may enhance Ca2+ releases, alter the dynamics of the Ca2- transient and prevent accumulation of Ca 2+ in the ER duringCa2+ overload. Expand
The tolbutamide site of SUR1 and a mechanism for its functional coupling to KATP channel closure
TLDR
The mechanism of inhibition of β‐cell KATP channels by sulfonylureas during treatment of non‐insulin‐dependent diabetes mellitus thus involves two components, drug‐binding and conformational changes within SUR1 which are coupled to the pore subunit through its N‐terminus and the disruption of nucleotide‐dependent stimulatory effects of the regulatory subunit on the pores. Expand
Repaglinide, a Novel, Short‐Acting Hypoglycemic Agent for Type 2 Diabetes Mellitus
TLDR
The agent's short duration of action may lessen the risk of long‐lasting hypoglycemia and of down‐regulation of β cell sensitivity (the latter promoting secondary drug failure), although data are sparse in this regard. Expand
Fate of3H- and14C-labelled A-4166 in pancreatic islets
TLDR
The findings suggest that the interaction of A-4166 with the beta-cell may be restricted to its insertion on the plasma membrane and binding to sulphonylurea receptors. Expand
The Role of Sulphonylureas in the Management of Type 2 Diabetes Mellitus
TLDR
Sulphonylureas are particularly beneficial when combined with agents such as metformin that decrease insulin resistance and Metformin and thiazolidinediones affect insulin sensitivity by independent mechanisms. Expand
...
1
2
3
...

References

SHOWING 1-10 OF 10 REFERENCES
Insulinotropic action of meglitinide analogs: concentration-response relationship and nutrient dependency.
TLDR
Iglitinide was a less efficient secretagogue than the other non-sulfonylurea hypoglycemic agents and augmented insulin release evoked by either 7 mM D-glucose or 10 microM succinic acid monomethyl ester (SAM). Expand
Combined effects of a calcium-agonist and hypoglycemic or hyperglycemic sulfonamides upon insulin release.
The organic calcium-agonist CGP 28392 augmented insulin release evoked by D-glucose in rat pancreatic islets incubated in the presence or absence of gliclazide, but failed to stimulate insulinExpand
Insulinotropic effect and possible mode of action of a new potent sulfonylurea (BS-4231).
TLDR
It is suggested that BS-4231 might accelerate within the beta-cell some step of glucose metabolism, which is rate-limiting when the insulin secretory process is not fully stimulated by extracellular glucose. Expand
A pyridothiadiazine (BPDZ 44) as a new and potent activator of ATP-sensitive K+ channels.
TLDR
The data suggest that BPDZ 44 inhibits the insulin releasing process by activating ATP-sensitive K+ channels, which will lead to a decrease in Ca2+ influx and reduction in [Ca2+]i. Expand
Stimulation of insulin release by non-sulfonylurea hypoglycemic agents: the meglitinide family.
  • W. Malaisse
  • Chemistry, Medicine
  • Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme
  • 1995
TLDR
Several new non-sulfonylurea hypoglycemic agents such as A-4166, KAD-1229 and repaglinide are structurally related to meglitinide, which exert little effect upon insulin release in nutrient-deprived islets, but markedly augment glucose-stimulated insulin release. Expand
Insulinotropic action of (2S)-2-benzyl-3-(cis-hexahydro-2-isoindolinylcarbonyl) propionate. I. Secretory and cationic aspects.
TLDR
The view that the mode of action of KAD-1229 displays analogy with that of hypoglycemic sulphonylurea is supported, as it increased insulin release evoked by 2-ketoisocaproate, albeit to a lesser extent than observed at a D-glucose concentration of comparable insulinotropic efficiency. Expand
Ionophoretic activity of meglitinide analogues.
TLDR
It is proposed that the ionophoretic capacity of meglitinide analogs may not represent an essential determinant of their insulin-releasing action and may not closely parallel the insulinotropic potential of these non-sulfonylurea hypoglycemic agents. Expand
Cytochalasin B-induced impariment of glucose metabolism in islets of Langerhans.
TLDR
It is suggested that cytochalasin B, possibly through its effect on the microfilamentous web which is part of the cell boundary, may both facilitate insulin release and inhibit glucose transport across the cell membrane, although no direct cause and effect relationship would exist between the two phenomena. Expand
Methods in diabetes research
Partial table of contents: Islet B-Cell Function in Human Subjects (W. Ward et al.) Assessment of Insulin Kinetics in Vivo (J. Radziuk and T. Morishima) Glucose Kinetics: Tracer Methods (E.Expand