Ranolazine for enhancing insulin secretion
A technology of insulin secretion and ranolazine, applied to endocrine system diseases, medical preparations containing active ingredients, organic active ingredients, etc., can solve the problems of decreased number of insulin receptors, dysfunction of signaling pathways, etc.
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Embodiment 1
[0242] Effects of ranolazine or ranolazine R- or S-enantiomer on GSIS in isolated rat islets
[0243] figure 1 The effect of ranolazine on GSIS in rat isolated islets is shown. Rat islets were isolated from male Sprague-Dawley (SD) rats (8-12 weeks old, n=6) and maintained overnight at full RPMI 1640 as described by YangZ.et al.Transplantation 2004, 77, 55-60 . Insulin secretion analysis was performed essentially as previously described by Liu D. et al. Steroids 2006, 71, 691-699. Briefly, before experiments, islets were incubated in Krebs-Ringer bicarbonate buffer (KRB; 129 mM NaCl, 4.8 mM KCl, 1.2 mM MgSO 4 , 1.2mM KH 2 PO 4 , 2.5mM CaCl 2 , 5mM NaHCO 3 , 0.1% BSA, 10mM HEPES, pH 7.4) pre-incubated for 30min, then washed the islets and incubated in 24-well plates in triplicate (50 islets / well), at 37°C in oxidized KRB buffer containing 3mM glucose or Incubate in 20 mM glucose for 60 min in the presence of various concentrations of ranolazine or vehicle. Insulin sec...
Embodiment 2
[0247] Effect of Ranolazine on Insulin Level in Rats
[0248] figure 2 Plasma insulin levels during an intravenous glucose tolerance test (IVGTT) performed in normal SD mice are shown. Each rat underwent IVGTT according to the method of Hendrick et al, Metabolism 42, (1): 1-6, 1993 . Rats were fasted overnight prior to test administration. One group of 11 mice was given saline only before the glucose load, while a second group of 7 mice was given ranolazine before the glucose load. Glucose was given at time 0, and ranolazine was given 30 min before glucose at a dose of 15 mg / kg body weight. Then blood insulin concentration was measured at -30, 0, 2, 4, 7, 15 and 30 min. As seen by plotting time versus baseline insulin levels, insulin levels were higher in ranolazine-treated rats compared to vehicle-treated rats.
Embodiment 3
[0250] Effects of Enantiomers of Ranolazine on Insulin Levels in Rats
[0251] image 3 Insulin levels during an intravenous glucose tolerance test (IVGTT) performed in normal SD rats are shown. The method used was as described in Example 2 above. As seen by plotting time versus baseline insulin levels, insulin levels were higher in rats treated with 15 mg / kg ranolazine R-enantiomer compared to vehicle treated rats. The insulin response to the S-enantiomer was different from vehicle-treated rats.
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