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Yun-Beom Sim Soo-Hyun Park Yu-Jung Kang Sung-Su Kim Chea-Ha Kim Su-Jin Kim Su-Min Lim Jun-Sub Jung Ohk-Hyun Ryu Moon-Gi Choi Hong-Won Suh 《The Korean journal of physiology & pharmacology》2013,17(6):493-497
We have recently demonstrated that some anti-diabetic drugs such as biguanide and thizolidinediones administered centrally modulate the blood glucose level, suggesting that orally administered anti-diabetic drugs may modulate the blood glucose level by acting on central nervous system. The present study was designed to explore the possible action of another class of anti-diabetic drugs, glinidies, administered centrally on the blood glucose level in ICR mice. Mice were administered intracerebroventricularly (i.c.v.) or intrathecally (i.t.) with 5 to 30 µg of repaglinide or nateglinide in D-glucose-fed and streptozotocin (STZ)-treated models. We found that i.c.v. or i.t. injection with repaglinide dose-dependently attenuated the blood glucose level in D-glucose-fed model, whereas i.c.v. or i.t. injection with nateglinide showed no modulatory action on the blood glucose level in D-glucose-fed model. Furthermore, the effect of repaglinide administered i.c.v. or i.t. on the blood glucose level in STZ-treated model was studied. We found that repaglinide administered i.c.v. slightly enhanced the blood glucose level in STZ-treated model. On the other hand, i.t. injection with repaglinide attenuated the blood glucose level in STZ-treated model. The plasma insulin level was enhanced by repaglinide in D-glucose-fed model, but repaglinide did not affect the plasma insulin level in STZ-treated model. In addition, nateglinide did not alter the plasma insulin level in both D-glucose-fed and STZ-treated models. These results suggest that the anti-diabetic action of repaglinide appears to be, at least, mediated via the brain and the spinal cord as revealed in both D-glucose fed and STZ-treated models. 相似文献
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Kyoko Kudo‐Fujimaki Takahisa Hirose Tomoaki Yoshihara Fumihiko Sato Yuki Someya Chie Ohmura Akio Kanazawa Yoshio Fujitani Hirotaka Watada 《Journal of diabetes investigation.》2014,5(4):400-409
Aims/Introduction
To investigate the efficacy and safety of vildagliptin, a potent dipeptidyl peptidase‐4 inhibitor, as add‐on to nateglinide, compared with switching to vildagliptin in Japanese type 2 diabetes patients poorly controlled with nateglinide.Materials and Methods
A total of 40 patients inadequately controlled with nateglinide were randomized to the switching group (n = 20, switching from nateglinide to vildagliptin) or combination group (n = 20, nateglinide plus vildagliptin). A meal tolerance test was carried out at weeks 0 and 24.Results
The mean changes in glycated hemoglobin from baseline to week 24 were −1.2 ± 0.3% and −0.3 ± 0.5% in patients of the combination and switching groups, respectively, and the difference between the groups was statistically significant (P < 0.001). The mean changes in area under the curve of glucose from 0 to 180 min (AUC0–180 min) from baseline to week 24 was −361 ± 271.3 mmol·min/L in patients of the combination group compared with 141 ± 241.9 mmol·min/L in those of the switching group (P < 0.001). The incidence of hypoglycemic events was low (three in the combination group), and none of the patients developed severe hypoglycemia. Although the addition of vildagliptin to nateglinide did not significantly increase insulin secretion relative to glucose elevation (ISG) after meal load (ISG0–180 min: AUC0–180 min insulin / AUC0–180 min glucose) in comparison with that in baseline, the mean ISG0–30 min 24 weeks after addition of vildagliptin to nateglinide was significantly higher than that at baseline. In contrast, switching from nateglinide to vildagliptin reduced the mean ISG0–180 min, relative to baseline.Conclusions
The combination therapy of vildagliptin and nateglinide is effective and safe in Japanese type 2 diabetes, and the improved glycemic control is as a result of augmentation of nateglinide‐induced early phase insulin secretion. This trial was registered with UMIN (no. ID000004010). 相似文献3.
Tsuyoshi Tanaka Hiroyuki Goto Rika Araki Mika Yamamoto Takashi Tanaka Ryoko Fujiwara Kazuya Murata 《Journal of diabetes investigation.》2014,5(2):199-205
Aims/Introduction
The efficacy and safety of sitagliptin, a dipeptidyl peptidase (DPP)‐4 inhibitor, were compared with those of glinides in Japanese patients with type 2 diabetes.Materials and Methods
The participants were 82 patients with type 2 diabetes (glycated hemoglobin [HbA1c] ≥6.0% and <10%) under treatment with glinides for glucose control. The participants were randomly assigned to a group (n = 44) receiving continuous treatment with glinides and a group (n = 38) switched to sitagliptin. Patients were followed for 12 weeks to evaluate glucose control. A meal tolerance test was carried out in weeks 0 and 12 to examine the pancreatic secretory response to postprandial hyperglycemia.Results
The changes in HbA1c from week 0 to week 12 were −0.25 and −0.05% in the sitagliptin and glinide groups, respectively, with a significant improvement with sitagliptin. The differences in fasting plasma glucose (FPG), glycoalbumin and 1,5‐anhydroglucitol between the two groups were 14.2 mg/dL, 0.7% and 1.7 μg/mL, respectively, showing significant improvements with sitagliptin. In the meal tolerance test, glucose at 0 min was lower in the sitagliptin group; however, there were no differences in glucose elevation at 30 and 60 min compared with 0 min. Plasma insulin and glucagon secretion at week 12 were significantly lower than at baseline in the sitagliptin group. Adverse events including hypoglycemia did not differ between the groups.Conclusions
FPG decreased and glucose control improved in patients who switched from glinides to sitagliptin. Sitagliptin decreased secretion of insulin and glucagon in a meal tolerance test compared with glinides, whereas the agents showed similar inhibition of postprandial hyperglycemia. This trial was registered with UMIN (UMIN‐CTR no. 000003479). 相似文献
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