Vildagliptin: an anti-diabetes agent ameliorates cognitive deficits and pathology observed in streptozotocin-induced Alzheimer's disease

Kosaraju, Jayasankar; Murthy, Vishakantha; Khatwal, Rizwan Basha; Dubala, Anil; Chinni, Santhivardhan; Nataraj, Satish Kumar Muthureddy; Basavan, Duraiswamy

doi:10.1111/jphp.12148

Cited by 125 publications

(82 citation statements)

References 51 publications

(91 reference statements)

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“…Peripherally‐administered exenatide and liraglutide prevented or improved memory performance in various rodent models of AD72, 73, 74, including in one late stage AD model75, and one diabetes‐related AD model76. Peripherally‐administered DPP‐4 inhibitors sitagliptin, vildagliptin and saxagliptin improved memory impairment in AD rodents77, 78, 79. In addition to these cognitive effects, incretins have beneficial effects on synaptic plasticity in rodent models of AD.…”

Section: Type 2 Diabetes Mellitus Dementia and Incretin‐based Therapiesmentioning

confidence: 99%

“…Peripherally‐administered liraglutide reduced both Aβ and APP levels72, even in a late‐stage AD rodent model75. Furthermore, peripherally‐administered sitagliptin, saxagliptin and vildagliptin lowered the levels of Aβ77, 78, 79. With regard to tau metabolism, studies in AD rodents showed that centrally‐administered (Val 8 )GLP‐168 and geniposide71, as well as peripherally‐administered exendin‐4 and liraglutide74, 76, reduced tau phosphorylation68, 71.…”

Section: Type 2 Diabetes Mellitus Dementia and Incretin‐based Therapiesmentioning

confidence: 99%

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Potentials of incretin‐based therapies in dementia and stroke in type 2 diabetes mellitus

Groeneveld

Kappelle

Biessels

2015

J of Diabetes Invest

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Patients with type 2 diabetes mellitus are at risk for accelerated cognitive decline and dementia. Furthermore, their risk of stroke is increased and their outcome after stroke is worse than in those without diabetes. Incretin‐based therapies are a class of antidiabetic agents that are of interest in relation to these cerebral complications of diabetes. Two classes of incretin‐based therapies are currently available: the glucagon‐like‐peptide‐1 agonists and the dipeptidyl peptidase‐4 ‐inhibitors. Independent of their glucose‐lowering effects, incretin‐based therapies might also have direct or indirect beneficial effects on the brain. In the present review, we discuss the potential of incretin‐based therapies in relation to dementia, in particular Alzheimer's disease, and stroke in patients with type 2 diabetes. Experimental studies on Alzheimer's disease have found beneficial effects of incretin‐based therapies on cognition, synaptic plasticity and metabolism of amyloid‐β and microtubule‐associated protein tau. Preclinical studies on incretin‐based therapies in stroke have shown an improved functional outcome, a reduction of infarct volume as well as neuroprotective and neurotrophic properties. Both with regard to the treatment of Alzheimer's disease, and with regard to prevention and treatment of stroke, randomized controlled trials in patients with or without diabetes are underway. In conclusion, experimental studies show promising results of incretin‐based therapies at improving the outcome of Alzheimer's disease and stroke through glucose‐independent pleiotropic effects on the brain. If these findings would indeed be confirmed in large clinical randomized controlled trials, this would have substantial impact.

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Section: Type 2 Diabetes Mellitus Dementia and Incretin‐based Therapiesmentioning

confidence: 99%

Section: Type 2 Diabetes Mellitus Dementia and Incretin‐based Therapiesmentioning

confidence: 99%

Potentials of incretin‐based therapies in dementia and stroke in type 2 diabetes mellitus

Groeneveld

Kappelle

Biessels

2015

J of Diabetes Invest

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“…As with GLP-1 analogues, DPP4 inhibitors have also shown promise in treatment of other conditions. Linagliptin has been shown to protect against stroke in animal models and both vildagliptin and saxagliptin attenuates the effects of steptozotocin induced-AD in rats [71][72][73].…”

Section: The Role Of Gip Glp-1 and Dpp4mentioning

confidence: 99%

Parkinson';s Disease, Diabetes and Cognitive Impairment

Ashraghi¹,

Pagano²,

Polychronis³

et al. 2016

EMI

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Patents published in the last 5 years could be used in novel approaches to Parkinson's treatment by targeting specific pathophysiology proteins, such as Nurr1, PINK1 and NrF2, while patents to improve penetration of the blood brain barrier could allow improved efficacy of existing treatments. Conclusion:Further studies using GLP-1 agonists and DPP-4 inhibitors to treat PD are warranted as they have shown promise.

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“…Vildagliptin, a DPP-4 inhibitor which increases circulating GLP-1 levels, has been shown to ameliorate the deposition of amyloid beta and tau phosphorylation in a streptozotosin induced animal model of diabetes [93] . A study by Omar et al [94] using a high fat diet induced obesity model in mice of advanced age has demonstrated that Vildagliptin confirms other rodent models of diabetes in preserving beta cell mass mainly through inducing beta cell proliferation and reducing beta cell apoptosis [94][95][96] .…”

Section: Dpp-4 Inhibitorsmentioning

confidence: 99%

“…Hypoglycaemia was significantly less in the patients taking DPP-4 inhibitors. These patients had significantly less transitory cerebral ischaemic attacks whereas other cardiovascular events were of borderline significance.There are 6 DPP-4 inhibitors (e.g., Sitigliptin, Linagliptin, Vildagliptin, Alogliptin, Saxagliptin, Teneligliptin) on the market minor variation in their chemical composition have not been translated to particular benefit although it should be noted that linagliptin is mostly excreted in pathways other than the kidney and hence dosage does not have to be reduced in moderate renal failure.Vildagliptin, a DPP-4 inhibitor which increases circulating GLP-1 levels, has been shown to ameliorate the deposition of amyloid beta and tau phosphorylation in a streptozotosin induced animal model of diabetes [93] . A study by Omar et al [94] using a high fat diet induced obesity model in mice of advanced age has demonstrated that Vildagliptin confirms other rodent models of diabetes in preserving beta cell mass mainly through inducing beta cell proliferation and reducing beta cell apoptosis [94][95][96] .…”

mentioning

confidence: 99%

Treatment of type 2 diabetes, lifestyle, GLP1 agonists and DPP4 inhibitors

Tomkin¹

2014

WJD

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Core tip: Treatment of diabetes is difficult. Initial success in achieving treatment goals is followed by deterioration and the necessity for additional treatments. Exciting new drugs with new modes of action, have stimulated diabetologists to strive for improved control in the knowledge that complications will be reduced or prevented. Obese patients, who loose weight on glucagon-like peptide-1 agonists are usually delighted with these drugs but for those who fail to loose weight changing to oral dipeptidyl peptidase-4 inhibitors would seem a good choice. sodium-glucose transporter-2 inhibitors have the added benefit of being effective even if blood sugar is near to target but uro-genital infection is a concern.Tomkin GH. Treatment of type 2 diabetes, lifestyle, GLP1 agonists and DPP4 inhibitors. World J Diabetes 2014; 5(5): 636-650 Available from: URL: http://www.wjgnet.com/1948-9358/full/ v5/i5/636.htm DOI: http://dx.doi.org/10. 4239/wjd.v5.i5.636 INTRODUCTIONReaders interested in diabetes must be sick and tired reading that diabetes is a global problem of immense size and getting worse by the day with predictions that we will all have the disease one day! I exaggerate of course but it is sad to realise that although we know so much more about the condition we have made little progress in reducing or conquering the disease. A recent history of diabetes in the past 200 years by Polonsky [1] gives an excellent review of the history of discovery of so many mechanisms that are faulty in diabetes and the number of Nobel prize winners who have contributed to such wonderful success, yet more and more people are being diagnosed with the condition/disease and the consequences are immense in terms of suffering and financial cost. One should not forget that before the discovery of insulin 90 years ago AbstractIn recent years the treatment focus for type 2 diabetes has shifted to prevention by lifestyle change and to more aggressive reduction of blood sugars during the early stage of treatment. Weight reduction is an important goal for many people with type 2 diabetes. Bariatric surgery is no longer considered a last resort treatment. Glucagon-like peptide-1 agonists given by injection are emerging as a useful treatment since they not only lower blood sugar but are associated with a modest weight reduction. The role of the oral dipeptidyl peptidase 4 inhibitors is emerging as second line treatment ahead of sulphonylureas due to a possible beneficial effect on the beta cell and weight neutrality. Drugs which inhibit glucose re-absorption in the kidney, sodium/glucose co-transport 2 inhibitors, may have a role in the treatment of diabetes. Insulin treatment still remains the cornerstone of treatment in many patients with type 2 diabetes.© 2014 Baishideng Publishing Group Inc. All rights reserved. 636October 15, 2014|Volume 5|Issue 5| WJD|www.wjgnet.com diabetes was a rapidly fatal disease and there was little interest in what we now term type 2 diabetes. Type 2 diabetes now makes up 90% of all diabetes. Insulin resist...

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Vildagliptin: an anti-diabetes agent ameliorates cognitive deficits and pathology observed in streptozotocin-induced Alzheimer's disease

Abstract: These robust therapeutic effects of vildagliptin demonstrate a unique mechanism for Aβ and tau clearance and reverse the cognitive deficits and pathology observed in AD.

Cited by 125 publications

References 51 publications

Potentials of incretin‐based therapies in dementia and stroke in type 2 diabetes mellitus

Potentials of incretin‐based therapies in dementia and stroke in type 2 diabetes mellitus

Parkinson';s Disease, Diabetes and Cognitive Impairment

Treatment of type 2 diabetes, lifestyle, GLP1 agonists and DPP4 inhibitors

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