Effect of D-Ala 2 GIP, a stable GIP receptor agonist on MPTP-induced neuronal impairments in mice

Glucose-Dependent Insulinotropic Polypeptide Mitigates 6-OHDA-Induced Behavioral Impairments in Parkinsonian Rats

“…In relation to PD, preclinically available long-acting GIP analogues have been evaluated in acute and chronic MPTP challenged mice. In these studies, they significantly ameliorated MPTP-induced neuroinflammation, oxidative stress and lipid peroxidation, elevated the expression of BDNF [ 26 , 27 ], reduced markers of dopaminergic loss in striatum and substantia nigra and, in accordance with our 6-OHDA rat study, improved behavioral measures [ 26 , 27 , 33 ].…”

“…This was achieved at a plasma active GIP concentration that is achievable in humans by use of a DPP-4 inhibitor [ 24 , 25 ]. To our knowledge, our study is the first to evaluate the action of GIP in a 6-OHDA PD animal model and adds to the growing literature that GIP may be of value as a treatment strategy for PD [ 26 , 27 ].…”

“…The progressive increase in apomorphine-induced rotations with repeated weekly tests evident within the saline group in our 6-OHDA MFB study likely is due to increasing sensitization of the denervated dopaminergic receptors. Notably, this sensitization was not seen in the GIP treated group ( Figure 5 ), likely reflecting an augmented dopaminergic input on the lesioned side [ 27 ]. In a number of studies involving dopaminergic grafts, an apomorphine challenge showed decreased rotation with repeated tests over time [ 39 ].…”

“…We assume that the GIP effects seen herein to mitigate behavioral deficits associated with dopaminergic lesioning were centrally mediated. Although several previous studies have reported favorable neurotrophic and neuroprotective actions of systemically administered, long-acting preclinical GIP analogues of similar amino acid size to GIP across multiple rodent models of neurodegeneration [ 6 , 23 , 26 , 27 , 33 , 37 , 44 ], the proportion of systemic GIP that enters the brain remains unclear. Our recent study of the 39 amino acid GLP-1 incretin mimetic, Exenatide, demonstrated that some 2% of plasma levels reach the brain [ 16 ].…”

Neuroprotective Effects and Treatment Potential of Incretin Mimetics in a Murine Model of Mild Traumatic Brain Injury

“…The pathophysiology of mTBI is complex and characterized especially by neuronal cell death and axonal damage induced primarily by the direct physical impact itself and secondarily by oxidative stress, neuroinflammation, mitochondrial dysfunction, DNA damage, and other pathological processes (Maas et al, 2008;Choe, 2016;McInnes et al, 2017). Since incretins have the capability to intervene in more than one of these pathological events (Perry et al, 2002;Nyberg et al, 2005;Iwai et al, 2006;Li et al, 2010b;Paratore et al, 2011;Yu et al, 2016;Verma et al, 2017), incretin mimetics have the potential to serve as neuroprotective agents following mTBI.…”