(15) Variant K of butyrylcholinesterase and types 1 And 2 of diabetes mellitus

Lepienski, Luís M.; Alcântara, Vânia M.; Souza, Ricardo Lehtonen Rodrigues de; Réa, Rosângela Roginski; Chautard‐Freire‐Maia, Eleidi A.

doi:10.1016/j.cbi.2005.10.060

Cited by 2 publications

(1 citation statement)

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“…BChE‐K as a risk factor for AD and T2DM has been the subject of much discussion, with studies divided regarding the association between this variant and the diseases [24, 46–51]. In our study we observed a lower incidence of the K‐variant in T2DM patients compared to controls.…”

Section: Discussionsupporting

confidence: 52%

Butyrylcholinesterase interactions with amylin may protect pancreatic cells in metabolic syndrome

Shenhar‐Tsarfaty¹,

Bruck²,

Bennett³

et al. 2011

Journal of Cellular and Molecular Medicine

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The metabolic syndrome (MetS) is a risk factor for type 2 diabetes mellitus (T2DM). However, the mechanisms underlying the transition from MetS to T2DM are unknown. Our goal was to study the potential contribution of butyrylcholinesterase (BChE) to this process. We first determined the hydrolytic activity of BChE in serum from MetS, T2DM and healthy individuals. The ‘Kalow’ variant of BChE (BChE-K), which has been proposed to be a risk factor for T2DM, was genotyped in the last two groups. Our results show that in MetS patients serum BChE activity is elevated compared to T2DM patients and healthy controls (P < 0.001). The BChE-K genotype showed similar prevalence in T2DM and healthy individuals, excluding this genotype as a risk factor for T2DM. However, the activity differences remained unexplained. Previous results from our laboratory have shown BChE to attenuate the formation of β-amyloid fibrils, and protect cultured neurons from their cytotoxicity. Therefore, we next studied the in vitro interactions between recombinant human butyrylcholinesterase and amylin by surface plasmon resonance, Thioflavine T fluorescence assay and cross-linking, and used cultured pancreatic β cells to test protection by BChE from amylin cytotoxicity. We demonstrate that BChE interacts with amylin through its core domain and efficiently attenuates both amylin fibril and oligomer formation. Furthermore, application of BChE to cultured β cells protects them from amylin cytotoxicity. Taken together, our results suggest that MetS-associated BChE increases could protect pancreatic β-cells in vivo by decreasing the formation of toxic amylin oligomers.

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Section: Discussionsupporting

confidence: 52%

Butyrylcholinesterase interactions with amylin may protect pancreatic cells in metabolic syndrome

Shenhar‐Tsarfaty¹,

Bruck²,

Bennett³

et al. 2011

Journal of Cellular and Molecular Medicine

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Butyrylcholinesterase genotype and gender influence Alzheimer's disease phenotype

Lane

2012

Alzheimer's & Dementia

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Retrospective data are presented to support a spectrum of early Alzheimer's disease (AD) along a continuum defined by gender and genotype. The putative neurodegenerative mechanisms driving distinct phenotypes at each end of the spectrum are glial hypoactivity associated with early failure of synaptic cholinergic neurotransmission and glial overactivation associated with loss of neural network connectivity due to accelerated age-related breakdown of myelin. In early AD, male butyrylcholinesterase K-variant carriers with one or two apolipoprotein ɛ4 alleles have prominent medial temporal atrophy, synaptic failure, cognitive decline, and accumulation of aggregated beta-amyloid peptide. Increasing synaptic acetylcholine in damaged but still functional cholinergic synapses improves cognitive symptoms, whereas increasing the ability of glia to support synapses and to clear beta-amyloid peptide might be disease-modifying. Conversely, chronic glial overactivation can also drive degenerative processes and in butyrylcholinesterase K-variant negative females generalized glial overactivation may be the main driver from mild cognitive impairment to AD. Females are more likely than males to have accelerated age-related myelin breakdown, more widespread white matter loss, loss of neural network connectivity, whole brain atrophy, and functional decline. Increasing extracellular acetylcholine levels blocks glial activation, reduces myelin loss and damage to neural network connectivity, and is disease-modifying. Between extremes characterized by gender, genotype, and age, pathophysiology may be mixed and this spectrum may explain much of the heterogeneity of amnestic mild cognitive impairment. Preservation of the functional integrity of the neural network may be an important component of strengthening cognitive reserve and significantly delaying the onset and progression of dementia, particularly in females. Prospective confirmation of these hypotheses is required. Implications for future research and therapeutic opportunities are discussed.

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(15) Variant K of butyrylcholinesterase and types 1 And 2 of diabetes mellitus

Cited by 2 publications

References 1 publication

Butyrylcholinesterase interactions with amylin may protect pancreatic cells in metabolic syndrome

Butyrylcholinesterase interactions with amylin may protect pancreatic cells in metabolic syndrome

Butyrylcholinesterase genotype and gender influence Alzheimer's disease phenotype

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