Animals ; Autophagy ; Diabetes Mellitus, Experimental/drug therapy* ; Mice ; Myocardium ; Sitagliptin Phosphate/pharmacology* ; Streptozocin

Animals ; Blood Glucose ; Diabetes Mellitus, Type 2/drug therapy* ; Insulin ; Insulin Resistance ; Islets of Langerhans ; Metformin/pharmacology* ; Mice ; Prediabetic State ; Sitagliptin Phosphate/pharmacology*

OBJECTIVE: To explore the impact of sitagliptin on aspirin resistance (AR) in patients with Type 2 diabetes mellitus (T2DM).
 METHODS: A total of 68 cases of AR were chosen from 136 cases of T2DM patients. The clinical data, including blood samples, fasting plasma glucose (FPG), glycosylated hemoglobin (HbAlc), and high sensitive C reactive protein (hs-CRP) were collected. Aenosine diphosphate (ADP) and arachidonic acid (AA) -induced platelet aggregation rate (PAG) were detected in 1, 3, 6 and 12 months after the treatment to evaluate the impact of sitagliptin on AR. 
 RESULTS: After 6 months of hypoglycemic treatment, FPG and HbAlc in two groups were at the normal level. The hypoglycemic effect was not obviously different (P>0.05), but the hsCRP and ADP or AA-induced PAG were decreased in the sitagliptin group with statistical significance when compared with the metformin group (P<0.05).
 CONCLUSION Sitagliptin can significantly improve the oxidative stress inflammatory state in T2DM patients and AR, which is independent on blood glucose control.
Aspirin ; pharmacology ; Blood Glucose ; analysis ; C-Reactive Protein ; analysis ; Diabetes Mellitus, Type 2 ; drug therapy ; Drug Resistance ; Glycated Hemoglobin A ; analysis ; Humans ; Hypoglycemic Agents ; pharmacology ; Metformin ; pharmacology ; Oxidative Stress ; Sitagliptin Phosphate ; pharmacology

OBJECTIVETo investigate the effects of the DPP4 inhibitor sitagliptin on the expressions of early growth response-1 (Egr-1) and fibronectin in the kidney of ApoE gene knockout mice.

METHODSEight-week-old male ApoE gene knockout mice were randomly divided into sitagliptin + apoE(-/-) group and apoE(-/-) group (n=6), with 6 C57BL mice as the normal control group. After feeding with high-fat diet and drug treatment for 16 weeks, the mice underwent intraperitoneal glucose tolerance test (IPGTT) and were measured for 24-h urinary albumin using ELISA. All the mice were then sacrificed to examine the changes of blood lipid profile and for detection of Egr-1 and fibronectin mRNA and proteins in the renal tissue using real-time PCR and Western blotting.

RESULTSThe mice in both apoE(-/-) group and sitagliptin+apoE(-/-) group all showed prominently increased blood lipids as compared with the control group (P<0.05) without significant differences between the two apoE(-/-) groups. The level of HDL was significantly higher in sitagliptin +apoE(-/-) group than in apoE(-/-) group (P<0.001) and control group (P<0.001). IPGTT showed no significant differences in the levels of blood glucose among the 3 groups. The excretion of urinary albumin was increased in apoE(-/-) group compared with the control group (P<0.01), but was significantly lower in sitagliptin+ apoE(-/-) group than in apoE(-/-) group (P<0.01). Real-time PCR and Western blotting showed significantly decreased mRNA and protein expressions of renal cortical Egr-1 and fibronectin in sitagliptin+apoE(-/-) group compared with apoE(-/-) group.

CONCLUSIONSitagliptin can reduce the renal expression of fibronectin by regulating the expression of Egr-1 to achieve renal protection.

Animals ; Apolipoproteins E ; genetics ; Diet, High-Fat ; Dipeptidyl-Peptidase IV Inhibitors ; pharmacology ; Early Growth Response Protein 1 ; metabolism ; Fibronectins ; metabolism ; Gene Knockout Techniques ; Kidney ; metabolism ; Lipids ; blood ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Real-Time Polymerase Chain Reaction ; Sitagliptin Phosphate ; pharmacology

To investigate the effect of berberine on glycemia regulation in rats with diabetes and the related mechanisms.Diabetic-like rat model was successfully induced by intraperitoneal injection of streptozotocin in 50 out of 60 male SD rats, which were then randomly divided into 5 groups with 10 rats in each:control group (received vehicle only), positive drug control group (sitagliptin 10 mg·kg·d), low-dose berberine group (30 mg·kg·d), moderate-dose berberine group (60 mg·kg·d), and high-dose berberine group (120 mg·kg·d). All animals were fed for 3 d, and fasting blood sampling was performed on day 3 of administration. Rats were given glucose (2 g/kg) by gavage 30 min after the last dose. Blood and intestinal samples were obtained 2 h after glucose loading. Fasting blood glucose (FBG) and 2-h postprandial plasma glucose (2h-PPG) were detected by using biochemical analyzer, and insulin, glucagon-like peptide-1 (GLP-1) and dipeptidyl peptidase-Ⅳ(DPP-Ⅳ) were measured by using ELISA kit.No significant difference in FBG and serum DPP-Ⅳ level were found between berberine groups and control group (all>0.05). Compared with control group, serum levels of GLP-1 and insulin were increased in high-and moderate-dose berberine groups, while 2h-PPG was decreased (all<0.05); GLP-1 levels in the intestinal samples were increased, while DPP-Ⅳ levels were decreased in all berberine groups (all<0.05).Short-term berberine administration can decrease 2h-PPG level in streptozotocin-induced diabetic rat model through local inhibition of intestinal DPP-Ⅳ. The efficacy of DPP-Ⅳ inhibitor may be associated with its intestinal pharmacokinetics.
Animals ; Berberine ; pharmacokinetics ; pharmacology ; Blood Glucose ; drug effects ; Diabetes Mellitus, Experimental ; chemically induced ; drug therapy ; Dipeptidyl Peptidase 4 ; analysis ; drug effects ; pharmacokinetics ; Dipeptidyl-Peptidase IV Inhibitors ; Dose-Response Relationship, Drug ; Glucagon-Like Peptide 1 ; analysis ; blood ; Hypoglycemic Agents ; Insulin ; blood ; Intestines ; chemistry ; drug effects ; Male ; Rats ; Rats, Sprague-Dawley ; Sitagliptin Phosphate