Is resveratrol a prospective therapeutic strategy in the co-association of glucose metabolism disorders and neurodegenerative diseases?

2021 ◽  
pp. 1-16
Author(s):  
R. Ribeiro ◽  
A. C. Santos ◽  
M. O. Calazans ◽  
A. C. P. De Oliveira ◽  
L. B . Vieira
2021 ◽  
Vol 7 (5) ◽  
pp. eabc5062
Author(s):  
Lei Cao ◽  
Siping Xiong ◽  
Zhiyuan Wu ◽  
Lei Ding ◽  
Yebo Zhou ◽  
...  

Na+/K+-ATPase (NKA) plays important roles in maintaining cellular homeostasis. Conversely, reduced NKA activity has been reported in aging and neurodegenerative diseases. However, little is known about the function of NKA in the pathogenesis of Parkinson’s disease (PD). Here, we report that reduction of NKA activity in NKAα1+/− mice aggravates α-synuclein–induced pathology, including a reduction in tyrosine hydroxylase (TH) and deficits in behavioral tests for memory, learning, and motor function. To reverse this effect, we generated an NKA-stabilizing monoclonal antibody, DR5-12D, against the DR region (897DVEDSYGQQWTYEQR911) of the NKAα1 subunit. We demonstrate that DR5-12D can ameliorate α-synuclein–induced TH loss and behavioral deficits by accelerating α-synuclein degradation in neurons. The underlying mechanism for the beneficial effects of DR5-12D involves activation of NKAα1-dependent autophagy via increased AMPK/mTOR/ULK1 pathway signaling. Cumulatively, this work demonstrates that NKA activity is neuroprotective and that pharmacological activation of this pathway represents a new therapeutic strategy for PD.


2018 ◽  
Vol 50 (05) ◽  
pp. 408-413 ◽  
Author(s):  
Sema Dogansen ◽  
Gulsah Yalin ◽  
Seher Tanrikulu ◽  
Sema Yarman

AbstractIn this study, we aimed to evaluate the presence of glucose metabolism abnormalities and their impact on IGF-1 levels in patients with acromegaly. Ninety-three patients with acromegaly (n=93; 52 males/41 females) were included in this study. Patients were separated into three groups such as; normal glucose tolerance (n=23, 25%), prediabetes (n=38, 41%), and diabetes mellitus (n=32, 34%). Insulin resistance was calculated with homeostasis model assessment (HOMA). HOMA-IR > 2.5 or ≤2.5 were defined as insulin resistant or noninsulin resistant groups, respectively. Groups were compared in terms of factors that may be associated with glucose metabolism abnormalities. IGF-1% ULN (upper limit of normal)/GH ratios were used to evaluate the impact of glucose metabolism abnormalities on IGF-1 levels. Patients with diabetes mellitus were significantly older with an increased frequency of hypertension (p<0.001, p=0.01, respectively). IGF-1% ULN/GH ratio was significantly lower in prediabetes group than in normal glucose tolerance group (p=0.04). Similarly IGF-1% ULN/GH ratio was significantly lower in insulin resistant group than in noninsulin resistant group (p=0.04). Baseline and suppressed GH levels were significantly higher in insulin resistant group than in noninsulin resistant group (p=0.024, p<0.001, respectively). IGF-1% ULN/GH ratio is a useful marker indicating glucose metabolism disorders and IGF-1 levels might be inappropriately lower in acromegalic patients with insulin resistance or prediabetes. We suggest that IGF-1 levels should be re-evaluated after the improvement of insulin resistance or glycemic regulation for the successful management of patients with acromegaly.


Author(s):  
Siqi Wu ◽  
Zhongli Chen ◽  
Li Yang ◽  
Yulin Zhang ◽  
Xiaohe Luo ◽  
...  

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Tian Yang ◽  
Xudan Yang ◽  
Luping Wang ◽  
Jun Mo

Abstract Background Agenesis of the dorsal pancreas (ADP) is clinically rare, and it is usually accompanied by abdominal pain. Various disorders of glucose metabolism associating with ADP have been reported, but there are only two studies reporting a correlation between ADP and DKA in English literature. Case presentation We present a case of a patient with ADP accompanied by abdominal pain and diabetic ketoacidosis as the initial clinical presentation. A 30-year-old man presented with a 3-month history of recurrent onset of persistent mild epigastric pain, which worsen when eating. Laboratory tests revealed metabolic acidosis, hyperglycemia, and ketonuria. Phase contrast CT and MRCP showed the absence of the body and tail of the pancreas, as well as the dorsal pancreatic duct. The C-peptide release test indicated β-cell dysfunction. A combination therapy of insulin, pancreatic enzyme supplements, and mosapride citrate were administrated and the pain gradually resolved. Conclusions As glucose metabolism disorders can vary across different individuals, we advise clinicians to consider the diagnosis of ADP for a patient who presents with a glucose metabolism disorder accompanied by abdominal pain, pancreatitis or steatorrhea.


HORMONES ◽  
2019 ◽  
Vol 19 (2) ◽  
pp. 135-143 ◽  
Author(s):  
Kalliopi J. Ioakim ◽  
Guy I. Sydney ◽  
Stavroula A. Paschou

2020 ◽  
Vol 21 (18) ◽  
pp. 6739
Author(s):  
Sharmeelavathi Krishnan ◽  
Yasaswi Shrestha ◽  
Dona P. W. Jayatunga ◽  
Sarah Rea ◽  
Ralph Martins ◽  
...  

Neurodegenerative diseases result in a range of conditions depending on the type of proteinopathy, genes affected or the location of the degeneration in the brain. Proteinopathies such as senile plaques and neurofibrillary tangles in the brain are prominent features of Alzheimer’s disease (AD). Autophagy is a highly regulated mechanism of eliminating dysfunctional organelles and proteins, and plays an important role in removing these pathogenic intracellular protein aggregates, not only in AD, but also in other neurodegenerative diseases. Activating autophagy is gaining interest as a potential therapeutic strategy for chronic diseases featuring protein aggregation and misfolding, including AD. Although autophagy activation is a promising intervention, over-activation of autophagy in neurodegenerative diseases that display impaired lysosomal clearance may accelerate pathology, suggesting that the success of any autophagy-based intervention is dependent on lysosomal clearance being functional. Additionally, the effects of autophagy activation may vary significantly depending on the physiological state of the cell, especially during proteotoxic stress and ageing. Growing evidence seems to favour a strategy of enhancing the efficacy of autophagy by preventing or reversing the impairments of the specific processes that are disrupted. Therefore, it is essential to understand the underlying causes of the autophagy defect in different neurodegenerative diseases to explore possible therapeutic approaches. This review will focus on the role of autophagy during stress and ageing, consequences that are linked to its activation and caveats in modulating this pathway as a treatment.


2020 ◽  
Vol 35 (4) ◽  
pp. 649-657 ◽  
Author(s):  
Toshiyuki Takahashi ◽  
Takayuki Okamoto ◽  
Yasuyuki Sato ◽  
Asako Hayashi ◽  
Yasuhiro Ueda ◽  
...  

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