‘Type 3’ diabetes: a brain insulin‐resistant state linked to Alzheimer's disease

Shaw, Ken

doi:10.1002/pdi.2115

Cited by 7 publications

(4 citation statements)

References 9 publications

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“…It has also recently been proposed that a common pathogenetic pathway connecting diabetes, subchronic inflammation, and AD may rely on the activation of the common pathogenetic pathway consisting of PTN-MK-RPTPβ/ζ Axis [9]. Strengthening the causal link between deregulated glycaemic homeostasis, including insulin secretion and resistance and AD, is the recent identification of a newly indicated form of diabetes named "type 3" diabetes that is characterized as a brain-insulin resistant state linked to AD [10]. Although the precise cellular type that develops insulin resistance in the brain has not yet been identified, recent studies suggest that cortical neurons develop resistance to insulin after prolonged exposure to high insulin concentrations.…”

Section: Pathogenetic Conceptsmentioning

confidence: 99%

The Role of Macrophage Migration Inhibitory Factor in Alzheimer′s Disease: Conventionally Pathogenetic or Unconventionally Protective?

et al. 2020

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Recent preclinical and clinical observations have offered relevant insights on the etiopathogenesis of late onset Alzheimer′s disease (AD) and upregulated immunoinflammatory events have been described as underlying mechanisms involved in the development of AD. Macrophage migration inhibitory factor (MIF) is a pleiotropic cytokine produced by several cells of the innate and adaptive immune system, as well as non-immune cells. In the present review, we highlight experimental, genetic, and clinical studies on MIF in rodent models of AD and AD patients, and we discuss emerging therapeutic opportunities for tailored modulation of the activity of MIF, that may potentially be applied to AD patients. Dismantling the exact role of MIF and its receptors in AD may offer novel diagnostic and therapeutic opportunities in AD.

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Section: Pathogenetic Conceptsmentioning

confidence: 99%

The Role of Macrophage Migration Inhibitory Factor in Alzheimer′s Disease: Conventionally Pathogenetic or Unconventionally Protective?

et al. 2020

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“…Each condition is treated by either agonists or replacement of the appropriate agent. A Practical Diabetes editorial leader has reviewed the emerging evidence of central metabolic dysfunction in T2DM, noting potentially pathogenic processes of chronic neuroinflammation, increased oxidative stress, and accumulation of toxic amyloid beta protein aggregates, seemingly associated with an underlying brain insulin‐resistant state. In comparison, PD is a neurodegenerative disorder, also associated with similar central pathogenic metabolic dysfunction, leading to loss of dopaminergic neurons in the substantia nigra.…”

Section: Shared Pathogenic Processesmentioning

confidence: 99%

Type 2 diabetes and Parkinson's disease

Shaw

2019

Practical Diabetes

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B y definition, common conditions commonly occur, and so the occurrence together of two relatively prevalent conditions, type 2 diabetes (T2DM) and Parkinson's disease (PD), might be considered simply by chance. Although the prevalence of T2DM (5% of UK population) is greater than that of PD (0.2% overall), both conditions increase with age, particularly PD (1% over 60 years; 5% over 85 years). Moreover, each shares some similarity in generally being as of later, slow onset and progressive in nature. As to causation, these two conditions, again, share similar concepts of genetic predisposition interacting with environmental factors in line with current understanding. So, by the laws of probability, it would be expected that these two conditions are likely to arise together in a proportion of either diabetes or Parkinson's disease clinics. But, when the two occur together, is it indeed a chance observation or is there a more significant association? With this in mind, it should be remembered that an association does not necessarily indicate a causal link in either direction, but it does raise interesting issues to consider in terms of respective relationships between the two conditions. Diabetes in Parkinson's diseaseFirstly, is there evidence that patients with PD have an increased risk of developing diabetes? Remarkably, in 1974 it was reported 1 that a large percentage of patients with PD had impaired glucose tolerance, and that 52.4% actually fulfilled criteria for the diagnosis of diabetes. However, a number of subsequent published studies, relatively few and small scale, proved inconclusive with no clear confirmation that diabetes occurred more frequently with PD. A US prospective study 2 of 1565 'older adults' (mean age 62 years!) with known PD identified diabetes in 12% of self-reported responders, but with a greater proportion of those with PD and diabetes duration over 10 years to indicate the complexity of the relationship.To date, the largest observational study 3 derived from the UK General Practice Research Database (1994)(1995)(1996)(1997)(1998)(1999)(2000)(2001)(2002)(2003)(2004)(2005) has found the prevalence of diabetes (all T2DM) to be similar for those with newly-diagnosed PD (8%; 90% aged over 60 years) compared to matched control patients without PD (8.5%). In a second part to the study, the risk of developing incident diabetes during follow-up was found to be lower with PD (relative risk [RR] 0.55). Although the time-scale for diagnosing diabetes following diagnosis of PD is not provided, the reduced risk appeared restricted to those using levodopa, the main treatment for PD. In our own prospective study 4 (1969-1979) of a cohort of 178 patients with idiopathic PD, we observed that life expectancy over a period of six years was normal in those able to tolerate sustained levodopa therapy. We observed a number of comorbidities, but did not identify diabetes as then of particular note. The evidence that diabetes occurs more frequently in people with PD remains inconclusive. Parkinson's disease ...

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“…Yet, the source of insulin in brain remains debated [30] . Streptozotocin (STZ), the nitrosamine-related compound was once injected ICV with a subdiabetogenic dose (3 mg/kg) in this work to simulate the environmental exposure to nitrosamines through smoking, diet and agriculture thus eliciting neurodegenerative changes and condition referred to as T3DM [31,32] . Since the available information about the histological changes of oral tissues in T3DM was very limited, this study aimed to investigate the T3DM-associated alterations of soft palatal mucosa in rats and to illustrate the effect of Zingiber extract oil on these alterations.…”

Section: Group IV (Zingiber)mentioning

confidence: 99%

The influence of Zingiber officinale Roscoe on the histological changes of soft palatal mucosa in streptozotocin-induced type 3 diabetes rat model

Saad

2019

Egyptian Journal of Histology

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Background: Zingiber officinale Roscoe presents valuable outcomes in some neurodegenerative diseases. Objective: This study aimed to evaluate Zingiber oil extract efficacy in the regression of Type3 diabetes mellitus (T3DM) induced in rat model. Methodology: 28 adult male albino rats were divided into four equal groups: Control-ve group received no injections; Control+ve group received a single bilateral intra-cerebroventricular (ICV) injection of sterile 0.9% saline, T3DM group received a single bilateral ICV injection of streptozotocin (3 mg/kg) dissolved in sterile 0.9% saline; Zingiber treated group five weeks after ICV-STZ, received orally 100 mg/kg/day Zingiber oil extract for two months. Soft palate oral mucosal sections were processed for H&E, fluorescence staining (using thioflavin-T dye) and immunohistochemical (using anticaspase-3 and anti-VEGF antibodies) examination. Results: Both control groups were almost identical. Some T3DM sections histopathologically displayed inflammatory signs represented by cloudy swelling of keratinocytes, nuclear degenerative signs, apparently increased apoptotic keratinocytes, subepithelial degeneration, chronic inflammatory infiltrates, congested dilated blood vessels, hyperplasia and dilatation of palatal glandular acini and excretory duct. Irregular and decreased palatal fungiform papillae with few vacuolated taste cells were illustrated. Comparing to control groups, significant strong diffuse thioflavin-T fluorescence in oral epithelium, palatal acini, endothelium of blood vessels along with subepithelial amyloid deposits in some T3DM specimens were detected. Likewise, caspase-3 immunoreactivity in oral epithelial and connective tissue cells significantly increased in T3DM group. Similarly, significant positivity to VEGF in oral epithelium and in the significantly increased blood vessels in wall thickness and distribution were exhibited in T3DM sections. All T3DM results were significantly restored in Zingiber group except for the low significant decrease of caspase-3 reactivity in this group. Conclusions: It was concluded that Zingiber oil extract was an appropriate selected approach to ameliorate the possible T3DM associated peripheral tissue insults but most probably in a higher dose or prolonged supplementation.

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‘Type 3’ diabetes: a brain insulin‐resistant state linked to Alzheimer's disease

Cited by 7 publications

References 9 publications

The Role of Macrophage Migration Inhibitory Factor in Alzheimer′s Disease: Conventionally Pathogenetic or Unconventionally Protective?

The Role of Macrophage Migration Inhibitory Factor in Alzheimer′s Disease: Conventionally Pathogenetic or Unconventionally Protective?

Type 2 diabetes and Parkinson's disease

The influence of Zingiber officinale Roscoe on the histological changes of soft palatal mucosa in streptozotocin-induced type 3 diabetes rat model

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