S15261 antagonises amylin‐induced impaired glucose tolerance

Espinal, J.; Lacour, F.; Berger, Sheldon; Duhault, J

doi:10.1016/0014-5793(95)00592-w

Cited by 3 publications

(1 citation statement)

References 34 publications

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“…In both rats and guinea pigs, administration of S 15261 produces a dose‐related (5–100 mg/kg) decrease in circulating glucose [1], due to a rapid increase in plasma insulin concentration. After repeated administration, S 15261 improves insulin sensitivity in animal models that have either genetically or dietary‐induced insulin resistance [2–5]. Chronic treatment with S 15261 restores the ability of insulin to increase peripheral glucose disposal in aged Sprague–Dawley rats (5 mg/kg/day for 14 days) [2].…”

Section: Introductionmentioning

confidence: 99%

Effects of S 15511, a therapeutic metabolite of the insulin‐sensitizing agent S 15261, in the Zucker Diabetic Fatty rat

Pickavance

Wilding

2006

Diabetes Obesity Metabolism

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Treatment with these agents in a genetic model of type 2 diabetes reveals that they all have a transient effect compared to the progressive worsening of vehicle-treated controls. The improvements in glucose metabolism observed with S 15511 are significant, however, suggesting it has more therapeutic activity than the Y 415 metabolite of S 15261. It is associated with less frequent progression to diabetes; i.e. Y 415 exerts a non-significant effect alone and no significant additive effect when combined with S 15511. The mechanism of action of S 15511 may be via increased insulin sensitivity and beta-cell response preservation up to day 21. Thus, previously reported insulin secretagogue effects are likely to be attributable to the parent compound.

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Section: Introductionmentioning

confidence: 99%

Effects of S 15511, a therapeutic metabolite of the insulin‐sensitizing agent S 15261, in the Zucker Diabetic Fatty rat

Pickavance

Wilding

2006

Diabetes Obesity Metabolism

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Amylin evokes protein p20 phosphorylation and insulin resistance in rat skeletal muscle extensor digitorum longus

Lee

Cooper

2002

Sci China Ser C

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In the present study, we investigate effect of amylin on the insulin sensitivity of rat skeletal muscle extensor digitorum longus (EDL) using in vitro intact muscle incubation in combination with metabolic radioactive labeling. The molecular basis of the amylin action was further examined using proteomic analysis. In particular, proteins of interest were characterized using an integrated microcharacterization procedure that involved in-gel trypsin digestion, organic solvent extraction, high performance liquid chromatography separation, microsequencing and microsequence analysis. We found that amylin significantly decreased the insulin-stimulated glucose incorporation into glycogen (p < 0.01) and produced a protein spot of approximately 20 ku in size. This amylin responsive protein (hereby designated as amylin responsive protein 1, APR1) was identified to be protein p20. Moreover, ARP1 spots on gels were found to consistently produce a corresponding radioactive spot on X-ray films in (32)Pi but not in (35)S-methionine labeling experiments. In conclusion, our results showed that in vitro amylin concomitantly evoked the production of ARP1 and caused insulin resistance in EDL muscle. It is suggested that protein p20 may be involved in amylin signal transduction and the appearance of ARP1 may be a step in a molecular pathway leading to the development of insulin resistance. ARP1 might therefore be a useful molecular marker for amylin action, insulin resistance and Type 2 diabetes.

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Insulin and lipid metabolism: new developments in drug therapy

Mackay

Petrie

1997

Expert Opinion on Investigational Drugs

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Current treatments for non-insulin-dependent diabetes mellitus (NIDDM) remain far from ideal. The presence of both hyperinsulinaemia and resistance to insulin action in NIDDM challenges the rationale of treatments which primarily boost insulin secretion. Novel therapeutic strategies focus mainly on increasing peripheral sensitivity to endogenous insulin, an approach which has the potential not only to treat, but also to prevent NIDDM in high-risk individuals. The most promising new agents are the thiazolidinedione derivatives, in particular troglitazone. Thiazolidinediones are ligands for a specific subtype of the peroxisome proliferator activated receptor (PPAR), and decrease plasma glucose levels in both obesity and NIDDM, while at the same time reducing circulating insulin and free fatty acid levels. The current development status of these agents is reviewed, along with an assessment of their potential in the prevention and treatment of diverse pathophysiological states characterised by insulin resistance, including atherosclerosis and polycystic ovarian disease. Reference is made to the current status of other experimental agents including hydantoin derivatives, (3)-adrenoceptor agonists, and inhibitors of lipolysis.

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S15261 antagonises amylin‐induced impaired glucose tolerance

Cited by 3 publications

References 34 publications

Effects of S 15511, a therapeutic metabolite of the insulin‐sensitizing agent S 15261, in the Zucker Diabetic Fatty rat

Effects of S 15511, a therapeutic metabolite of the insulin‐sensitizing agent S 15261, in the Zucker Diabetic Fatty rat

Amylin evokes protein p20 phosphorylation and insulin resistance in rat skeletal muscle extensor digitorum longus

Insulin and lipid metabolism: new developments in drug therapy

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