High Prevalence of Undiagnosed Insulin Resistance in Non-Diabetic Subjects with Parkinson’s Disease

Hogg, Elliot; Athreya, Kishore; Basile, Christina; Tan, Echo; Kamiński, Jan P.; Tagliati, Michele

doi:10.3233/jpd-181305

Cited by 61 publications

(40 citation statements)

References 47 publications

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“…Insulin signaling impairment and insulin resistance have been observed in neurodegenerative diseases such as AD (Talbot et al, 2012) and PD (Hogg et al, 2018) (Figure 2). Diabetes mellitus, FIGURE 2 | The connection between insulin signaling and neurodegenerative disease.…”

Section: Insulin In Neurodegenerative Diseasementioning

confidence: 99%

Role of Insulin in Neurotrauma and Neurodegeneration: A Review

et al. 2020

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Insulin is a hormone typically associated with pancreatic release and blood sugar regulation. The brain was long thought to be "insulin-independent," but research has shown that insulin receptors (IR) are expressed on neurons, microglia and astrocytes, among other cells. The effects of insulin on cells within the central nervous system are varied, and can include both metabolic and non-metabolic functions. Emerging data suggests that insulin can improve neuronal survival or recovery after trauma or during neurodegenerative diseases. Further, data suggests a strong antiinflammatory component of insulin, which may also play a role in both neurotrauma and neurodegeneration. As a result, administration of exogenous insulin, either via systemic or intranasal routes, is an increasing area of focus in research in neurotrauma and neurodegenerative disorders. This review will explore the literature to date on the role of insulin in neurotrauma and neurodegeneration, with a focus on traumatic brain injury (TBI), spinal cord injury (SCI), Alzheimer's disease (AD) and Parkinson's disease (PD).

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Section: Insulin In Neurodegenerative Diseasementioning

confidence: 99%

Role of Insulin in Neurotrauma and Neurodegeneration: A Review

et al. 2020

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“…The PD network module associated with insulin resistance is not preserved in HCs. Insulin resistance is increasingly being shown to be important in PD as a potential therapeutic target [29] and has a high prevalence in non-diabetic PD patients [30], additionally insulin receptor signaling pathways are disturbed in PD [11]. Within this module we identified HDAC6 as a hub gene which promotes the formation of inclusions from α-synuclein toxic oligomers [31].…”

Section: Discussionmentioning

confidence: 99%

Genetic networks in Parkinson’s and Alzheimer’s disease

Kelly

Moyeed

Carroll

et al. 2020

Aging

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Parkinson's disease (PD) and Alzheimer's disease (AD) are the most common neurodegenerative diseases and there is increasing evidence that they share common physiological and pathological links. Here we have conducted the largest network analysis of PD and AD based on their gene expressions in blood to date. We identified modules that were not preserved between disease and healthy control (HC) networks, and important hub genes and transcription factors (TFs) in these modules. We highlighted that the PD module not preserved in HCs was associated with insulin resistance, and HDAC6 was identified as a hub gene in this module which may have the role of influencing tau phosphorylation and autophagic flux in neurodegenerative disease. The AD module associated with regulation of lipolysis in adipocytes and neuroactive ligand-receptor interaction was not preserved in healthy and mild cognitive impairment networks and the key hubs TRPC5 and BRAP identified as potential targets for therapeutic treatments of AD. Our study demonstrated that PD and AD share common disrupted genetics and identified novel pathways, hub genes and TFs that may be new areas for mechanistic study and important targets in both diseases.

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“…Among the seven phenotypes in this subcluster, several were known to be correlated based on previous epidemiological studies. For example, in addition to the connection between fasting insulin and breast cancer discussed above, insulin was linked to several phenotypes in this cluster: 1) there is a high prevalence of insulin resistance in non-diabetic Parkinson's disease patients [67] ; 2) it was suggested that abnormal insulin signaling underlies increased autism risk based on the evidence that mutations that hyperactivate PI3K pathway cause autism [68]; 3) insulin resistance co-occurs with hypertension [69]; 4) insulin may work to stimulate osteoblast differentiation, and diabetes have a higher risk of bone fracture [70]. These evidences suggest that insulin signaling may be one of the physiological processes that connect these phenotypes together.…”

Section: Two Way Bi-clustering Detects Subsets Of Genes Co-associatedmentioning

confidence: 93%

An integrative analysis of GWAS and intermediate molecular trait data reveals common molecular mechanisms supporting genetic similarity between seemingly unrelated complex traits

J¹,

Fuller²,

Zheng³

et al. 2019

Preprint

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The rapid accumulation of Genome Wide Association Studies (GWAS) and association studies of intermediate molecular traits provides new opportunities for comparative analysis of the genetic basis of complex human phenotypes. Using a newly developed statistical framework called Sherlock-II that integrates GWAS with eQTL (expression Quantitative Trait Loci) and metabolite-QTL data, we systematically analyzed 445 GWAS datasets, and identified 1371 significant gene-phenotype associations and 308 metabolites-phenotype associations (passing a Q value cutoff of 1/3). This integrative analysis allows us to translate SNP-phenotype associations into functionally informative gene-phenotype association profiles. Genetic similarity analyses based on these profiles clustered phenotypes into sub-trees that reveal both expected and unexpected relationships. We employed a statistical approach to delineate sets of functionally related genes that contribute to the similarity between their association profiles. This approach suggested common molecular mechanisms that connect the phenotypes in a subtree.For example, we found that fasting insulin, fasting glucose, breast cancer, prostate cancer, and lung cancer clustered into a subtree, and identified cyclic AMP/GMP signaling that connects breast cancer and insulin, NAPDH oxidase/ROS generation that connects the three cancers, and apoptosis that connects all five phenotypes. Our approach can be used to assess genetic similarity and suggest mechanistic connections between phenotypes. It has the potential to improve the diagnosis and treatment of a disease by mapping mechanistic insights from one phenotype onto others based on common molecular underpinnings.

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High Prevalence of Undiagnosed Insulin Resistance in Non-Diabetic Subjects with Parkinson’s Disease

Abstract: IR is prevalent in PD and it correlates with BMI. A correlation between IR with cognitive and QoL measures cannot be determined on the basis of this sample.

Cited by 61 publications

References 47 publications

Role of Insulin in Neurotrauma and Neurodegeneration: A Review

Role of Insulin in Neurotrauma and Neurodegeneration: A Review

Genetic networks in Parkinson’s and Alzheimer’s disease

An integrative analysis of GWAS and intermediate molecular trait data reveals common molecular mechanisms supporting genetic similarity between seemingly unrelated complex traits

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