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#28481334   2017/05/08 Save this To Up

Liraglutide reduces body weight by upregulation of adenylate cyclase 3.

According to recent studies, adenylate cyclase 3 (AC3) is associated with obesity. Liraglutide reduces blood glucose levels and body weight (BW). We performed a 2 × 2 factorial experiment to study the relationships among AC3, liraglutide and obesity and to obtain a more comprehensive understanding of the mechanisms underlying the physiological effects of liraglutide on obesity.

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#28087908   2017/01/14 Save this To Up

[Berberine regulates glycemia via local inhibition of intestinal dipeptidyl peptidase-Ⅳ].

Objective: To investigate the effect of berberine on glycemia regulation in rats with diabetes and the related mechanisms. Methods: 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(-1)·d(-1)), low-dose berberine group (30 mg·kg(-1)·d(-1)), moderate-dose berberine group (60 mg·kg(-1)·d(-1)), and high-dose berberine group (120 mg·kg(-1)·d(-1)). 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. Results: No significant difference in FBG and serum DPP-Ⅳ level were found between berberine groups and control group (all P>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 P<0.05); GLP-1 levels in the intestinal samples were increased, while DPP-Ⅳ levels were decreased in all berberine groups (all P<0.05). Conclusions: 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.

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#26279440   2015/08/17 Save this To Up

The Neuroprotective Effect of Liraglutide is Mediated by Glucagon-Like Peptide 1 Receptor-Mediated Activation of cAMP/PKA/CREB Pathway.

Glucagon-like peptide-1 (GLP-1)-based drugs are being used to achieve better glucose control in patients with type 2 diabetes, and GLP-1 mimetics such as liraglutide have shown therapeutic potential in preventing diabetes-related microvascular and macrovascular complications as well as comorbidities such as neurodegenerative disorders. In the present study, we investigated the effects of liraglutide on primary rat cortical astrocytes treated with advanced glycation end-products (AGEs).

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#22948814   2012/10/05 Save this To Up

Combination of mangiferin and dipeptidyl peptidase-4 inhibitor sitagliptin improves impaired glucose tolerance in streptozotocin-diabetic rats.

In this study, we combined the dipeptidyl peptidase-4 inhibitor sitagliptin with the antidiabetic drug mangiferin to examine the effects on active glucagon-like peptide-1 (GLP-1) and glucose tolerance in streptozotocin-diabetic rats. Active GLP-1 levels were measured by an ELISA kit. Insulin levels were measured by an RIA kit. Islet morphology was determined by double immunolabeling. Sitagliptin (1 mg/kg) or mangiferin (20 mg/kg) single treatment improved glucose tolerance during an oral glucose tolerance test. In addition, the combination therapy improved glucose tolerance with an increase in plasma insulin level and active GLP-1 levels. Islets from combination-treated diabetic rats had markedly increased β-cell/islet area ratio compared with islets from the diabetic or single-treatment rats. In conclusion, these results indicate that the combination therapy is useful as a therapeutic agent for impaired glucose tolerance and type 2 diabetes.

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#18996945   2009/02/03 Save this To Up

Berberine promotes glucagon-like peptide-1 (7-36) amide secretion in streptozotocin-induced diabetic rats.

Berberine (BBR), a hypoglycemic agent, has shown beneficial metabolic effects for anti-diabetes, but its precise mechanism was unclear. Glucagon-like peptide-1 (GLP-1) is considered to be an important incretin that can decrease hyperglycemia in the gastrointestinal tract after meals. The aim of this study was to investigate whether BBR exerts its anti-diabetic effects via modulating GCG secretion. Diabetes-like rats induced by streptozotocin received BBR (120 mg/kg per day, i.g) for 5 weeks. Two hours following the last dose, the rats were anaesthetized and received 2.5 g/kg glucose by gavage. At 15-minute and 30-minute after glucose load, blood samples, pancreas, and intestines were obtained to measure insulin and GCG using ELISA kit. The number of L cells in the ileum and beta-cells in the pancreas were identified using immunohistology. The expression of proglucagon mRNA in the ileum was measured by RT-PCR. The results indicated that BBR treatment significantly increased GCG levels in plasma and intestine (P<0.05) accompanied with the increase of proglucagon mRNA expression and the number of L-cell compared with the controls (P<0.05). Furthermore, BBR increased insulin levels in plasma and pancreas as well as beta-cell number in pancreas. The data support the hypothesis that the anti-diabetic effects of BBR may partly result from enhancing GCG secretion.

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