A novel GIP-oxyntomodulin hybrid peptide acting through GIP, glucagon and GLP-1 receptors exhibits weight reducing and anti-diabetic properties

Bhat, Vikas K.; Kerr, Barry D.; Flatt, Peter R.; Gault, Victor

doi:10.1016/j.bcp.2013.03.009

Cited by 70 publications

(45 citation statements)

References 31 publications

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“…The novel GIP-OXM hybrid peptide also acts through GIP, glucagon, and GLP-1Rs. Acute administration of d-Ala 2 GIP-OXM to HFD mice resulted in reduced plasma glucose, increased insulin concentrations, and reduced body weight (Bhat et al, 2013a). In addition, others (Gault et al, 2013) also have constructed a series of novel GLP-1/ GIP/glucagon hybrid peptides through the fusion of the key amino acid sequences of GLP-1, GIP, and glucagon known to be important for biological activity.…”

Section: Triagonists For Glp-1 Gip and Gcgr Triagonists And T2dmmentioning

confidence: 98%

Incretin-based therapy for type 2 diabetes mellitus is promising for treating neurodegenerative diseases

Hölscher

2016

Reviews in the Neurosciences

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AbstractIncretin hormones include glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP). Due to their promising action on insulinotropic secretion and improving insulin resistance (IR), incretin-based therapies have become a new class of antidiabetic agents for the treatment of type 2 diabetes mellitus (T2DM). Recently, the links between neurodegenerative diseases and T2DM have been identified in a number of studies, which suggested that shared mechanisms, such as insulin dysregulation or IR, may underlie these conditions. Therefore, the effects of incretins in neurodegenerative diseases have been extensively investigated. Protease-resistant long-lasting GLP-1 mimetics such as lixisenatide, liraglutide, and exenatide not only have demonstrated promising effects for treating neurodegenerative diseases in preclinical studies but also have shown first positive results in Alzheimer’s disease (AD) and Parkinson’s disease (PD) patients in clinical trials. Furthermore, the effects of other related incretin-based therapies such as GIP agonists, dipeptidyl peptidase-IV (DPP-IV) inhibitors, oxyntomodulin (OXM), dual GLP-1/GIP, and triple GLP-1/GIP/glucagon receptor agonists on neurodegenerative diseases have been tested in preclinical studies. Incretin-based therapies are a promising approach for treating neurodegenerative diseases.

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Section: Triagonists For Glp-1 Gip and Gcgr Triagonists And T2dmmentioning

confidence: 98%

Incretin-based therapy for type 2 diabetes mellitus is promising for treating neurodegenerative diseases

Hölscher

2016

Reviews in the Neurosciences

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“…These benefits of GLP‐1 have led to widespread clinical use of incretin mimetics, such as exenatide (Byetta) and the GLP‐1 receptor (GLP‐1R) agonist liraglutide (Victoza) . Coupled with this, there may be further therapeutic benefits from simultaneous activation of two or more receptor signalling pathways for the glucagon‐secretin family of peptides, including glucagon, glucose‐dependent insulinotropic polypeptide (GIP) as well as CCK‐8 . This has resulted in a growing interest in the use of dual or triple co‐agonist peptides that could enhance multiple metabolic pathways and provide better and more physiological treatment options …”

Section: Introductionmentioning

confidence: 99%

Dogfish glucagon analogues counter hyperglycaemia and enhance both insulin secretion and action in diet‐induced obese diabetic mice

O’Harte

Lynch

et al. 2016

Diabetes Obesity Metabolism

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“…Thus, combinatorial hormone therapies [90] or protease-resistant peptides able to interact with multiple receptors have been designed. Among these coagonists, glucagon (GCGR)-GLP-1R coagonists [91][92][93], GLP-1R/gastrin receptor dual agonist (ZP-3022) [94], GIP/GLP-1/glucagon triple receptoragonists [95][96][97], GLP-1/amilyn dual agonists [98,99] were shown to be active in animal models of obesity. Among these, a protease resistant dual GLP-1R/GCGR agonist showed to be active in obese, nondiabetic rhesus monkeys, without a concomitant diabetogenic effect that could be caused by GCGR agonist activity [100].…”

Section: Combination Therapymentioning

confidence: 99%

New Perspectives on the Development of Antiobesity Drugs

Costantino

Barlocco

2015

Future Med. Chem.

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After many years of research, obesity is still a disease with an unmet medical need. Very few compounds have been approved, acting mainly on neuromediators; researches, in recent years, pointed toward compounds potentially safer than first-generation antiobesity drugs, able to interact with one or more (multitarget therapy) receptors for substances produced by the gut, adipose tissue and other targets outside CNS. Other holistic approaches, such as those involving gut microbiota and plant extracts, appeared recently in the literature, and undoubtedly will contribute to the discovery of a valuable therapy for this disease. This review deals with the positive results and the pitfalls obtained following these approaches, with a view on their clinical trial studies.

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A novel GIP-oxyntomodulin hybrid peptide acting through GIP, glucagon and GLP-1 receptors exhibits weight reducing and anti-diabetic properties

Cited by 70 publications

References 31 publications

Incretin-based therapy for type 2 diabetes mellitus is promising for treating neurodegenerative diseases

Incretin-based therapy for type 2 diabetes mellitus is promising for treating neurodegenerative diseases

Dogfish glucagon analogues counter hyperglycaemia and enhance both insulin secretion and action in diet‐induced obese diabetic mice

New Perspectives on the Development of Antiobesity Drugs

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