Neuronal human BACE1 knockin induces systemic diabetes in mice

Kaja Pluci??ska; Ruta Dekeryte; David Koss; Kirsty Shearer; Nimesh Mody; Phillip D. Whitfield; Mary K. Doherty; Marco Mingarelli; Andy Welch; Gernot Riedel; Mirela Delibegovic; Bettina Platt; Phillip Whitfield

doi:10.1007/s00125-016-3960-1

Neuronal human BACE1 knockin induces systemic diabetes in mice

Kaja Pluci??ska, Ruta Dekeryte, David Koss, Kirsty Shearer, Nimesh Mody, Phillip D. Whitfield, Mary K. Doherty, Marco Mingarelli, Andy Welch, Gernot Riedel, Mirela Delibegovic, Bettina Platt, Phillip Whitfield

Research output: Contribution to journal › Article › peer-review

52 Citations (Scopus)

256 Downloads (Pure)

Abstract

Aims
β-Secretase 1 (BACE1) is a key enzyme in Alzheimer’s disease pathogenesis that catalyses the amyloidogenic cleavage of amyloid precursor protein (APP). Recently, global Bace1 deletion was shown to protect against diet-induced obesity and diabetes, suggesting that BACE1 is a potential regulator of glucose homeostasis. Here, we investigated whether increased neuronal BACE1 is sufficient to alter systemic glucose metabolism, using a neuron-specific human BACE1 knockin mouse model (PLB4).
Methods
Glucose homeostasis and adiposity were determined by glucose tolerance tests and EchoMRI, lipid species were measured by quantitative lipidomics, and biochemical and molecular alterations were assessed by western blotting, quantitative PCR and ELISAs. Glucose uptake in the brain and upper body was measured via 18FDG-PET imaging.
Conclusions/interpretation
Our data reveal that neuronal BACE1 is a key regulator of metabolic homeostasis and provide a potential mechanism for the high prevalence of metabolic disturbance in Alzheimer’s disease.

Original language	English
Pages (from-to)	1513–1523
Number of pages	10
Journal	Diabetologia
Volume	59
DOIs	https://doi.org/10.1007/s00125-016-3960-1
Publication status	Published - 2 May 2016

Keywords

3ref2021

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1007/s00125-016-3960-1Licence: CC BY-ND

Plucinska_et_al_Diabetologia_2016Final published version, 1.43 MBLicence: CC BY-ND

http://link.springer.com/10.1007/s00125-016-3960-1

Cite this

@article{61b1cb02db2f4bb497590d15b422ef14,

title = "Neuronal human BACE1 knockin induces systemic diabetes in mice",

abstract = "Aimsβ-Secretase 1 (BACE1) is a key enzyme in Alzheimer{\textquoteright}s disease pathogenesis that catalyses the amyloidogenic cleavage of amyloid precursor protein (APP). Recently, global Bace1 deletion was shown to protect against diet-induced obesity and diabetes, suggesting that BACE1 is a potential regulator of glucose homeostasis. Here, we investigated whether increased neuronal BACE1 is sufficient to alter systemic glucose metabolism, using a neuron-specific human BACE1 knockin mouse model (PLB4).MethodsGlucose homeostasis and adiposity were determined by glucose tolerance tests and EchoMRI, lipid species were measured by quantitative lipidomics, and biochemical and molecular alterations were assessed by western blotting, quantitative PCR and ELISAs. Glucose uptake in the brain and upper body was measured via 18FDG-PET imaging.Conclusions/interpretationOur data reveal that neuronal BACE1 is a key regulator of metabolic homeostasis and provide a potential mechanism for the high prevalence of metabolic disturbance in Alzheimer{\textquoteright}s disease.",

keywords = "3ref2021",

author = "Kaja Pluci??ska and Ruta Dekeryte and David Koss and Kirsty Shearer and Nimesh Mody and Whitfield, {Phillip D.} and Doherty, {Mary K.} and Marco Mingarelli and Andy Welch and Gernot Riedel and Mirela Delibegovic and Bettina Platt and Phillip Whitfield",

year = "2016",

month = may,

day = "2",

doi = "10.1007/s00125-016-3960-1",

language = "English",

volume = "59",

pages = "1513–1523",

journal = "Diabetologia",

issn = "0012-186X",

publisher = "Springer Science and Business Media Deutschland GmbH",

}

TY - JOUR

T1 - Neuronal human BACE1 knockin induces systemic diabetes in mice

AU - Pluci??ska, Kaja

AU - Dekeryte, Ruta

AU - Koss, David

AU - Shearer, Kirsty

AU - Mody, Nimesh

AU - Whitfield, Phillip D.

AU - Doherty, Mary K.

AU - Mingarelli, Marco

AU - Welch, Andy

AU - Riedel, Gernot

AU - Delibegovic, Mirela

AU - Platt, Bettina

AU - Whitfield, Phillip

PY - 2016/5/2

Y1 - 2016/5/2

N2 - Aimsβ-Secretase 1 (BACE1) is a key enzyme in Alzheimer’s disease pathogenesis that catalyses the amyloidogenic cleavage of amyloid precursor protein (APP). Recently, global Bace1 deletion was shown to protect against diet-induced obesity and diabetes, suggesting that BACE1 is a potential regulator of glucose homeostasis. Here, we investigated whether increased neuronal BACE1 is sufficient to alter systemic glucose metabolism, using a neuron-specific human BACE1 knockin mouse model (PLB4).MethodsGlucose homeostasis and adiposity were determined by glucose tolerance tests and EchoMRI, lipid species were measured by quantitative lipidomics, and biochemical and molecular alterations were assessed by western blotting, quantitative PCR and ELISAs. Glucose uptake in the brain and upper body was measured via 18FDG-PET imaging.Conclusions/interpretationOur data reveal that neuronal BACE1 is a key regulator of metabolic homeostasis and provide a potential mechanism for the high prevalence of metabolic disturbance in Alzheimer’s disease.

AB - Aimsβ-Secretase 1 (BACE1) is a key enzyme in Alzheimer’s disease pathogenesis that catalyses the amyloidogenic cleavage of amyloid precursor protein (APP). Recently, global Bace1 deletion was shown to protect against diet-induced obesity and diabetes, suggesting that BACE1 is a potential regulator of glucose homeostasis. Here, we investigated whether increased neuronal BACE1 is sufficient to alter systemic glucose metabolism, using a neuron-specific human BACE1 knockin mouse model (PLB4).MethodsGlucose homeostasis and adiposity were determined by glucose tolerance tests and EchoMRI, lipid species were measured by quantitative lipidomics, and biochemical and molecular alterations were assessed by western blotting, quantitative PCR and ELISAs. Glucose uptake in the brain and upper body was measured via 18FDG-PET imaging.Conclusions/interpretationOur data reveal that neuronal BACE1 is a key regulator of metabolic homeostasis and provide a potential mechanism for the high prevalence of metabolic disturbance in Alzheimer’s disease.

KW - 3ref2021

U2 - 10.1007/s00125-016-3960-1

DO - 10.1007/s00125-016-3960-1

M3 - Article

SN - 0012-186X

VL - 59

SP - 1513

EP - 1523

JO - Diabetologia

JF - Diabetologia

ER -

Neuronal human BACE1 knockin induces systemic diabetes in mice

Abstract

Keywords

UN SDGs

Access to Document

Fingerprint

Cite this