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Liraglutide ameliorates beta-cell function, alleviates oxidative stress and inhibits low grade inflammation in young patients with new-onset type 2 diabetes.

ABSTRACT: BackgroundThe prevalence of type 2 diabetes in youth is escalating rapidly. We aimed to evaluate the effects of liraglutide on beta-cell function, metabolic productions of oxidative stress, low grade inflammation compared with metformin in young patients with recent onset type 2 diabetes mellitus.MethodsSixty patients were randomly assigned to receive 8-week liraglutide or metformin treatment. Beta-cell function was assessed by modified beta cell function index (MBCI), early phase of insulin secretion index (?I30/?G30), proinsuin to insulin ratio (P/I) and the insulin area under the curve (AUCins). The expression of 8-OH-dG and 8-iso-PGF2? and hs-C-reactive protein (hs-CRP) were measured as indications of oxidative stress and low grade inflammation.ResultsAfter 8 weeks liraglutide treatment, MBCI, ?I30/?G30, AUCins significantly increased, 8-OH-dG, 8-iso-PGF2?, P/I and hs-CRP remarkably reduced. The differences before and after 8-week liraglutide treatment in ?MBCI (11.1 [2.81, 43.08] vs 0.00 [??8.16, 10.47], P?=?0.017), ?LN?I30/?G30 (0.44 [0.04, 0.85] vs ??0.09 [??0.33, 0.36], P?=?0.049), ?AUCins (117 [??8, 376] vs ??21 [??314, 109] mIU/L, P?=?0.013), ?P/I (??0.05 [??0.09, ??0.03] vs ??0.02 [??0.04, 0.01], P?=?0.026)were remarkably enhanced compared to those of the metformin therapy. The expression of 8-OH-dG, 8-iso-PGF2? and hs-CRP also decreased after 8-week metformin treatment.ConclusionsThese data demonstrated that liraglutide administration was more effective on ameliorating beta-cell function than metformin treatment in young patients with new-onset type 2 diabetes mellitus. Both liraglutide and metformin could alleviate the level of oxidative stress and attenuate low grade inflammatory, we speculate this effect may not the main mechanism of beta-cell function improvement by liraglutide in diabetic patients.Trial registration Chinese Clinical Trials registry, chiCTR1800018008, Registered 27 August 2018—retrospectively registered.Electronic supplementary materialThe online version of this article (10.1186/s13098-018-0392-8) contains supplementary material, which is available to authorized users.

SUBMITTER: Zhang W

PROVIDER: S-EPMC6296090 | biostudies-other | 2018

REPOSITORIES: biostudies-other

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Project description:Background:Erectile dysfunction (ED) occurs more frequently and causes a worse response to the first-line therapies in diabetics compared with nondiabetic men. Corpus cavernosum vascular dysfunction plays a pivotal role in the occurrence of diabetes mellitus ED (DMED). The aim of this study was to investigate the protective effects of glucagon-like peptide-1 (GLP-1) analog liraglutide on ED and explore the underlying mechanisms in vivo and in vitro. Methods:Type 1 diabetes was induced in rats by streptozotocin, and the apomorphine test was for screening the DMED model in diabetic rats. Then they were randomly treated with subcutaneous injections of liraglutide (0.3 mg/kg/12 h) for 4 weeks. Erectile function was assessed by cavernous nerve electrostimulation. The corpus cavernosum was used for further study. In vitro, effects of liraglutide were evaluated by primary corpus cavernosum smooth muscle cells (CCSMCs) exposed to low or high glucose (HG)-containing medium with or without liraglutide and GLP-1 receptor (GLP-1R) inhibitor. Western blotting, fluorescent probe, immunohistochemistry, and relevant assay kits were performed to measure the levels of target proteins. Results:Administration of liraglutide did not significantly affect plasma glucose and body weights in diabetic rats, but improved erectile function, reduced levels of NADPH oxidases and ROS production, downregulated expression of Ras homolog gene family (RhoA) and Rho-associated protein kinase (ROCK) 2 in the DMED group dramatically. The liraglutide treatment promoted autophagy further and restored expression of GLP-1R in the DMED group. Besides, cultured CCSMCs with liraglutide exhibited a lower level of oxidative stress accompanied by inhibition of the RhoA/ROCK pathway and a higher level of autophagy compared with HG treatment. These beneficial effects of liraglutide effectively reversed by GLP-1R inhibitor. Conclusion:Liraglutide exerts protective effects on ED associated with the regulation of smooth muscle dysfunction, oxidative stress and autophagy, independently of a glucose- lowering effect. It provides new insight into the extrapancreatic actions of liraglutide and preclinical evidence for a potential treatment for DMED.

Project description:BackgroundSterculia tragacantha is a medicinal plant commonly used in the western part of Nigeria, for managing diabetes mellitus. However, there is a dearth of scientific information on the antidiabetic and neuroprotective properties of the plant.MethodsThe in silico, in vitro and in vivo models were used to evaluate the antioxidants, antidiabetic, anti-inflammatory and neuroprotective potential of aqueous extract of Sterculia tragacantha leaf (AESTL) in streptozotocin (STZ)-induced diabetic rats. Thirty (30) male albino rats (155.34±6.33 g) were intraperitoneal injected with 40 mg/kg of freshly prepared streptozotocin and were divided into 5 groups (A-E) of 6 animals each. Groups A-D were treated with 0, 150 and 300 mg/kg of AESTL, and 200 mg/kg body weight of metformin respectively, while group E serve as the normal control.ResultsThe results of in vitro analysis revealed dose-dependent antioxidant activities; ABTS (IC50 = 63.03±2.57 μg/mL), DPPH (117.49±2.35 μg/mL), FRAP (15.19±0.98 mmol/100g), TAC (43.38±0.96 mg/100g), hypoglycaemic effect; α-amylase (IC50 = 77.21±4.35 μg/mL) and α-glucosidase (IC50 = 443.25±12.35), and anti-cholinesterase; AChE (IC50 = 113.07±3.42 μg/mL) and BChE (IC50 = 87.50±4.32 μg/mL) activities of AESTL. In vivo study revealed dose-dependent hypoglycemic effect and body weight improvement in rats treated with the AESTL. In addition, AESTL improved the antioxidant status and attenuated STZ-induced dysregulations of Na+-K+-ATPase, cholinesterases and neurotransmitters in the brain tissue of experimental rats. The results also demonstrated that AESTL could regulate anti-inflammatory response via inhibition of COX-2/NO signaling axis in the brain of diabetic rats. Molecular docking analysis revealed that epicatechin and procyanidin B2, the bioactive compounds from AESTL, docked well to the binding cavities of acetylcholinesterase, butyrylcholinesterase, α-amylase and α-glucosidase with binding affinities ranges between -8.0 and -11.4 kcal/mol, suggesting that these compounds are the bioactive component that could be responsible for the antidiabetic and neuroprotective activities of AESTL.ConclusionThe results of the present study strongly suggested that the AESTL extract could be very useful for halting diabetes progression and its associated neuroinflammation complications.

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Liraglutide ameliorates beta-cell function, alleviates oxidative stress and inhibits low grade inflammation in young patients with new-onset type 2 diabetes.

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