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Butyrylcholinesterase interactions with amylin may protect pancreatic cells in metabolic syndrome.

Shenhar-Tsarfaty S, Bruck T, Bennett ER, Bravman T, Aassayag EB, Waiskopf N, Rogowski O, Bornstein N, Berliner S, Soreq H - J. Cell. Mol. Med. (2011)

Bottom Line: However, the activity differences remained unexplained.We demonstrate that BChE interacts with amylin through its core domain and efficiently attenuates both amylin fibril and oligomer formation.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurology and Internal Medicine, Tel Aviv Sourasky Medical Center, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.

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Cholinergic activity and risk factors in MetS patients. (A)–(D) Cholinergic activity (A–B, BChE; C–D, AChE) versus the number of MetS components, according to gender, represented as bar graphs ± S.E.M. (0 represents individuals with no components, >3 represents individuals with four or five components). One-way anova was used to compare groups, P < 0.001. (E) and (F) The interaction of triglyceride levels and waist circumference with cholinergic activity. Bar graphs represent mean cholinergic status ± S.E.M. for each combination of factors, by gender (E, men; F, women). (G) and (H) BChE activity in tertiles of C-reactive protein. Bar graphs represent the mean calculated BChE activity ± S.E.M., by gender (G, men; H, women).
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fig01: Cholinergic activity and risk factors in MetS patients. (A)–(D) Cholinergic activity (A–B, BChE; C–D, AChE) versus the number of MetS components, according to gender, represented as bar graphs ± S.E.M. (0 represents individuals with no components, >3 represents individuals with four or five components). One-way anova was used to compare groups, P < 0.001. (E) and (F) The interaction of triglyceride levels and waist circumference with cholinergic activity. Bar graphs represent mean cholinergic status ± S.E.M. for each combination of factors, by gender (E, men; F, women). (G) and (H) BChE activity in tertiles of C-reactive protein. Bar graphs represent the mean calculated BChE activity ± S.E.M., by gender (G, men; H, women).

Mentions: BChE activity was measured in sera from the first cohort (see ‘Materials and methods’), comprising 146 MetS patients and 429 healthy individuals. We observed considerably higher circulation BChE activity in the MetS patients in comparison to the controls: 1345.7 ± 368 nmol/min.*ml versus 1101.3 ± 348 nmol/min.*ml, respectively (P < 0.001, Table 1). This was compatible with the notion of impaired parasympathetic activity in MetS patients due to increased ACh degradation. We noted a gender difference regarding several of the known risk factors for T2DM in this cohort: Men presented higher serum cholinesterase activities than women, accompanied by higher BMI, CRP, systolic and diastolic blood pressure and frequencies of hypertension and dyslipidaemia, (Fig. 1G and H, and Tables S1 and S2). BChE activity, more than AChE activity, was correlated significantly with several dysmetabolism risk factors and tested biomarkers (Table S3). Moreover, patients with more components of the MetS showed significantly higher BChE activities in a component number-dependent manner, in both genders (Fig. 1A–D). This demonstrated the association of parasympathetic impairment with dysglycaemia, hyperlipidaemia, aging, obesity and hypertension. Significant interaction effects were also noted between waist circumference and triglyceride levels, and were shown to reflect increased BChE activity, also following adjustment for age and smoking status (Fig. 1E and F). Another explanation for the elevated BChE in the MetS patients could be an inadvertent bias in patient selection relating to BMI status: previous findings from our group show a positive correlation between BChE activity and BMI status [34, 35]. An additional possible bias is the difference in medication intake between the two groups. These potential biases were not evaluated in the current study, and further longitudinal studies would be needed to assess them.


Butyrylcholinesterase interactions with amylin may protect pancreatic cells in metabolic syndrome.

Shenhar-Tsarfaty S, Bruck T, Bennett ER, Bravman T, Aassayag EB, Waiskopf N, Rogowski O, Bornstein N, Berliner S, Soreq H - J. Cell. Mol. Med. (2011)

Cholinergic activity and risk factors in MetS patients. (A)–(D) Cholinergic activity (A–B, BChE; C–D, AChE) versus the number of MetS components, according to gender, represented as bar graphs ± S.E.M. (0 represents individuals with no components, >3 represents individuals with four or five components). One-way anova was used to compare groups, P < 0.001. (E) and (F) The interaction of triglyceride levels and waist circumference with cholinergic activity. Bar graphs represent mean cholinergic status ± S.E.M. for each combination of factors, by gender (E, men; F, women). (G) and (H) BChE activity in tertiles of C-reactive protein. Bar graphs represent the mean calculated BChE activity ± S.E.M., by gender (G, men; H, women).
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4373355&req=5

fig01: Cholinergic activity and risk factors in MetS patients. (A)–(D) Cholinergic activity (A–B, BChE; C–D, AChE) versus the number of MetS components, according to gender, represented as bar graphs ± S.E.M. (0 represents individuals with no components, >3 represents individuals with four or five components). One-way anova was used to compare groups, P < 0.001. (E) and (F) The interaction of triglyceride levels and waist circumference with cholinergic activity. Bar graphs represent mean cholinergic status ± S.E.M. for each combination of factors, by gender (E, men; F, women). (G) and (H) BChE activity in tertiles of C-reactive protein. Bar graphs represent the mean calculated BChE activity ± S.E.M., by gender (G, men; H, women).
Mentions: BChE activity was measured in sera from the first cohort (see ‘Materials and methods’), comprising 146 MetS patients and 429 healthy individuals. We observed considerably higher circulation BChE activity in the MetS patients in comparison to the controls: 1345.7 ± 368 nmol/min.*ml versus 1101.3 ± 348 nmol/min.*ml, respectively (P < 0.001, Table 1). This was compatible with the notion of impaired parasympathetic activity in MetS patients due to increased ACh degradation. We noted a gender difference regarding several of the known risk factors for T2DM in this cohort: Men presented higher serum cholinesterase activities than women, accompanied by higher BMI, CRP, systolic and diastolic blood pressure and frequencies of hypertension and dyslipidaemia, (Fig. 1G and H, and Tables S1 and S2). BChE activity, more than AChE activity, was correlated significantly with several dysmetabolism risk factors and tested biomarkers (Table S3). Moreover, patients with more components of the MetS showed significantly higher BChE activities in a component number-dependent manner, in both genders (Fig. 1A–D). This demonstrated the association of parasympathetic impairment with dysglycaemia, hyperlipidaemia, aging, obesity and hypertension. Significant interaction effects were also noted between waist circumference and triglyceride levels, and were shown to reflect increased BChE activity, also following adjustment for age and smoking status (Fig. 1E and F). Another explanation for the elevated BChE in the MetS patients could be an inadvertent bias in patient selection relating to BMI status: previous findings from our group show a positive correlation between BChE activity and BMI status [34, 35]. An additional possible bias is the difference in medication intake between the two groups. These potential biases were not evaluated in the current study, and further longitudinal studies would be needed to assess them.

Bottom Line: However, the activity differences remained unexplained.We demonstrate that BChE interacts with amylin through its core domain and efficiently attenuates both amylin fibril and oligomer formation.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurology and Internal Medicine, Tel Aviv Sourasky Medical Center, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.

Show MeSH
Related in: MedlinePlus