Effect of amylin on memory and central insulin resistance in a rat model of Alzheimer’s disease

Nassar, Seham Zakaria; Badae, Noha Mohamed; Issa, Yasmine Amr

doi:10.1080/13813455.2018.1534244

Cited by 20 publications

(15 citation statements)

References 62 publications

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“…Accordingly, exogenous administration of amylin analog or pharmacological activator of amylin receptors may be potentially employed as therapeutic agents in alleviating the increased tendency of ischemia-reperfusion-induced myocardial injury in diabetic patients. There have been studies showing the beneficial effects of pramlintide in improving learning and memory in an animal model of Alzheimer's disease [16]. To best of our knowledge, it is the first study showing the potential of pramlintide in preventing vascular dysfunction and exaggerated form of ischemia-reperfusion-induced myocardial injury in diabetic rats.…”

Section: Discussionmentioning

confidence: 94%

“…The ELISA kits employed in the present study included connexin 43 (LifeSpan BioSciences, U.S.A.) and amylin (LifeSpan BioSciences, U.S.A.). The doses of water-soluble, non-peptide amylin agonist, pramlintide [16], H 2 S donor, NaHS [34], and gap-junctional blocker, carbenoxolone (20 mg and 40 mg/kg) [35] were selected on the basis of previous studies.…”

Section: Animals Drugs and Chemicalsmentioning

confidence: 99%

“…Apart from regulating the glucose levels, amylin has also been proposed to reduce the β-amyloid burden and improve cognitive functions [15]. A recent study has shown that pramlintide improves learning and memory in an animal model of dementia [16]. It may be possible that the excessive circulating amylin (associated with hyperinsulinemia) may produce deleterious effects by depositing on the tissues/organs.…”

Section: Introductionmentioning

confidence: 99%

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Involvement of amylin B-H2S-connexin 43 signaling pathway in vascular dysfunction and enhanced ischemia–reperfusion-induced myocardial injury in diabetic rats

et al. 2020

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The present study was designed to investigate the role of amylin, H2S, and connexin 43 in vascular dysfunction and enhanced ischemia–reperfusion (I/R)-induced myocardial injury in diabetic rats. A single dose of streptozotocin (65 mg/kg) was employed to induce diabetes mellitus. After 8 weeks, there was a significant decrease in the plasma levels of amylin, an increase in I/R injury to isolated hearts (increase in CK-MB and cardiac troponin release) on the Langendorff apparatus. Moreover, there was a significant impairment in vascular endothelium function as assessed by quantifying acetylcholine-induced relaxation in norepinephrine-precontracted mesenteric arteries. There was also a marked decrease in the expression of H2S and connexin 43 in the hearts following I/R injury in diabetic rats. Treatment with amylin agonist, pramlintide (100 and 200 µg/kg), and H2S donor, NaHS (10 and 20 μmol/kg) for 2 weeks improved the vascular endothelium function, abolished enhanced myocardial injury and restored the levels of H2S along with connexin 43 in diabetic animals. However, pramlintide and NaHS failed to produce these effects the presence of gap junction blocker, carbenoxolone (20 and 40 mg/kg). Carbenoxolone also abolished the myocardial levels of connexin 43 without affecting the plasma levels of amylin and myocardial levels of H2S. The decrease in the amylin levels with a consequent reduction in H2S and connexin 43 may contribute to inducing vascular dysfunction and enhancing I/R-induced myocardial injury in diabetic rats.

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Section: Discussionmentioning

confidence: 94%

Section: Animals Drugs and Chemicalsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Involvement of amylin B-H2S-connexin 43 signaling pathway in vascular dysfunction and enhanced ischemia–reperfusion-induced myocardial injury in diabetic rats

et al. 2020

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“…Such a comparison is not possible in PD models since insulin signalling in the brain has not been explored earlier than 7 days following 6-OHDA/MPTP treatment (Wilcox et al 1989). Additionally, from that time-point onward, impaired insulin and dopaminergic signalling in the brain (and in the striatum and hippocampus in particular) have been detected both in AD and PD models Lester-Coll et al 2006;Grünblatt et al 2007;Morris et al 2008;Deng et al 2009;Agrawal et al 2010;Shonesy et al 2012;Lee et al 2014;Barilar et al 2015;Knezovic et al 2015Knezovic et al , 2017Hu et al 2018;Rabie et al 2018;Gupta et al 2018;Wang et al 2018a, b;Nassar et al 2018). On one side, there is decreased IR expression in astrocytes and neurons already 1 h after STZ application, and STZ-induced mitochondrial damage manifested during 24 h following STZ-icv treatment (Amiri et al 2017;Knezovic et al 2017).…”

Section: Insulin and Dopamine Signalling Interplay In Non-transgenic mentioning

confidence: 99%

“…Considering the elements downstream the IR signalling cascade in the STZicv model, dysfunctionality was observed rather consistently across the studies of different research groups and at different time-points from 1 week up to 9 months post-STZicv treatment (Table 1). Different parameters ranging from decreased tyrosine phosphorylation of IR, through serine phosphorylation of IRS1, decreased PI3K and AKT phosphorylation, to consequently increased GSK3 activity, were explored and demonstrated starting from 1 week onward following STZ-icv treatment (Table 1) Deng et al 2009;Shonesy et al 2012;Barilar et al 2015;Gupta et al 2018;Nassar et al 2018;Wang et al 2018a, b). A 9-month follow up study indicated that neurochemical changes related to insulinergic signalling in the hippocampus, including the alterations in IDE and gene expression, seem to follow a biphasic pattern Barilar et al 2015); an acute response emphasized up to 1 month post-treatment, followed by a slow progressive chronic phase seen at > 3 month time-points, which positively correlated with cognitive impairment .…”

Section: Time Course Of the Appearance Of Insulin Signalling Dysfunctmentioning

confidence: 99%

Shared cerebral metabolic pathology in non-transgenic animal models of Alzheimer's and Parkinson's disease

et al. 2020

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Parkinson's disease (PD) and Alzheimer's disease (AD) are the most common chronic neurodegenerative disorders, characterized by motoric dysfunction or cognitive decline in the early stage, respectively, but often by both symptoms in the advanced stage. Among underlying molecular pathologies that PD and AD patients have in common, more attention is recently paid to the central metabolic dysfunction presented as insulin resistant brain state (IRBS) and altered cerebral glucose metabolism, both also explored in animal models of these diseases. This review aims to compare IRBS and alterations in cerebral glucose metabolism in representative non-transgenic animal PD and AD models. The comparison is based on the selectivity of the neurotoxins which cause experimental PD and AD, towards the cellular membrane and intracellular molecular targets as well as towards the selective neurons/non-neuronal cells, and the particular brain regions. Mitochondrial damage and coexpression of insulin receptors, glucose transporter-2 and dopamine transporter on the membrane of particular neurons as well as astrocytes seem to be the key points which are further discussed in a context of alterations in insulin signalling in the brain and its interaction with dopaminergic transmission, particularly regarding the time frame of the experimental AD/ PD pathology appearance and the correlation with cognitive and motor symptoms. Such a perspective provides evidence on IRBS being a common underlying metabolic pathology and a contributor to neurodegenerative processes in representative non-transgenic animal PD and AD models, instead of being a direct cause of a particular neurodegenerative disorder.Publisher's Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

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Neurodegeneration in type 2 diabetes: Alzheimer's as a case study

2020

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Introduction Rigorous research in the last few years has shown that in addition to the classical mechanism of neurodegeneration, certain unconventional mechanisms may also lead to neurodegenerative disease. One of them is a widely studied metabolic disorder: type 2 diabetes mellitus (T2DM). We now have a clear understanding of glucose‐mediated neurodegeneration, mostly from studies in Alzheimer's disease (AD) models. AD is recognized to be significantly associated with hyperglycemia, even earning the term “type 3 diabetes.” Here, we review first the pathophysiology of AD, both from the perspective of classical protein accumulation, as well as the newer T2DM‐dependent mechanisms supported by findings from patients with T2DM. Secondly, we review the different pathways through which neurodegeneration is aggravated in hyperglycemic conditions taking AD as a case study. Finally, some of the current advances in AD management as a result of recent research developments in metabolic disorders‐driven neurodegeneration are also discussed. Methods Relevant literatures found from PubMed search were reviewed. Results Apart from the known causes of AD, type 2 diabetes opens a new window to the AD pathology in several ways. It is a bidirectional interaction, of which, the molecular and signaling mechanisms are recently studied. This is our attempt to connect all of them to draw a complete mechanistic explanation for the neurodegeneration in T2DM. Refer to Figure 3. Conclusion The perspective of AD as a classical neurodegenerative disease is changing, and it is now being looked at from a zoomed‐out perspective. The correlation between T2DM and AD is something observed and studied extensively. It is promising to know that there are certain advances in AD management following these studies.

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Effect of amylin on memory and central insulin resistance in a rat model of Alzheimer’s disease

Cited by 20 publications

References 62 publications

Involvement of amylin B-H2S-connexin 43 signaling pathway in vascular dysfunction and enhanced ischemia–reperfusion-induced myocardial injury in diabetic rats

Involvement of amylin B-H2S-connexin 43 signaling pathway in vascular dysfunction and enhanced ischemia–reperfusion-induced myocardial injury in diabetic rats

Shared cerebral metabolic pathology in non-transgenic animal models of Alzheimer's and Parkinson's disease

Neurodegeneration in type 2 diabetes: Alzheimer's as a case study

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