General Information:

Id: 613
Diseases: Diabetes mellitus, type II - [OMIM]
Insulin resistance
Mammalia
article
Reference: Chen Y et al.(2009) Antidiabetic drug metformin (GlucophageR) increases biogenesis of Alzheimers amyloid peptides via up-regulating BACE1 transcription Proc Natl Acad Sci U S A 106: 3907-3912 [PMID: 19237574]

Interaction Information:

Comment In N2a neuroblastoma cells stably expressing human APP (N2a695) metformin treatment increased the levels of both intracellular and extracellular A-beta-40/42 in a dose-dependent manner, similar effects were seen in primary cortical neurons.
Formal Description
Interaction-ID: 3245

drug/chemical compound

Metformin

increases_quantity of

in a dose-dependent manner
Drugbank entries Show/Hide entries for Metformin
Comment In N2a neuroblastoma cells stably expressing human APP (N2a695) metformin treatment increased the levels of both intracellular and extracellular A-beta-40/42 in a dose-dependent manner, similar effects were seen in primary cortical neurons.
Formal Description
Interaction-ID: 3253

drug/chemical compound

Metformin

increases_quantity of

in a dose-dependent manner
Drugbank entries Show/Hide entries for Metformin
Comment Metformin reduced alpha-cleavage and promoted beta-cleavage, as evidenced by decreased sAPP-alpha and increased APP C-terminal fragment, CTF-beta (the upper CTF band that resulted from cleavage by BACE1).
Formal Description
Interaction-ID: 3254

drug/chemical compound

Metformin

decreases_quantity of

gene/protein

sAPP-alpha

Drugbank entries Show/Hide entries for Metformin
Comment Metformin reduced alpha-cleavage and promoted beta-cleavage, as evidenced by decreased sAPP-alpha and increased APP C-terminal fragment, CTF-beta (the upper CTF band that resulted from cleavage by BACE1).
Formal Description
Interaction-ID: 3255

drug/chemical compound

Metformin

increases_quantity of

Drugbank entries Show/Hide entries for Metformin
Comment Metformin reduced alpha-cleavage and promoted beta-cleavage, as evidenced by decreased sAPP-alpha and increased APP C-terminal fragment, CTF-beta (the upper CTF band that resulted from cleavage by BACE1).
Formal Description
Interaction-ID: 3256

drug/chemical compound

Metformin

increases_quantity of

gene/protein

CTF-beta

Drugbank entries Show/Hide entries for Metformin
Comment Metformin did not change the levels of full-length PS1 (presenilin 1, the core component of gamma-secretase) or its N-terminal fragment.
Formal Description
Interaction-ID: 3257

drug/chemical compound

Metformin

NOT affects_quantity of

gene/protein

PSEN1

Drugbank entries Show/Hide entries for Metformin
Comment Metformin did not change the levels of full-length PS1 (presenilin 1, the core component of gamma-secretase) or its N-terminal fragment.
Formal Description
Interaction-ID: 3258

drug/chemical compound

Metformin

NOT affects_quantity of

Drugbank entries Show/Hide entries for Metformin
Comment Metformin had no effect on two enzymes known to degrade A-beta, neprilysin and insulin-degrading enzyme (IDE), including protein levels and their activities.
Formal Description
Interaction-ID: 3261

drug/chemical compound

Metformin

NOT affects_activity of

gene/protein

MME

Drugbank entries Show/Hide entries for Metformin or MME
Comment Metformin had no effect on two enzymes known to degrade A-beta, neprilysin and insulin-degrading enzyme (IDE), including protein levels and their activities.
Formal Description
Interaction-ID: 3262

drug/chemical compound

Metformin

NOT affects_quantity of

gene/protein

MME

Drugbank entries Show/Hide entries for Metformin or MME
Comment Metformin had no effect on two enzymes known to degrade A-beta, neprilysin and insulin-degrading enzyme (IDE), including protein levels and their activities.
Formal Description
Interaction-ID: 3263

drug/chemical compound

Metformin

NOT affects_activity of

gene/protein

IDE

Drugbank entries Show/Hide entries for Metformin or IDE
Comment Metformin had no effect on two enzymes known to degrade A-beta, neprilysin and insulin-degrading enzyme (IDE), including protein levels and their activities.
Formal Description
Interaction-ID: 3264

drug/chemical compound

Metformin

NOT affects_quantity of

gene/protein

IDE

Drugbank entries Show/Hide entries for Metformin or IDE
Comment Metformin had no effect on A-beta degradation.
Formal Description
Interaction-ID: 3265

drug/chemical compound

Metformin

NOT affects_activity of

process

beta-amyloid catabolic process

Drugbank entries Show/Hide entries for Metformin
Comment The increased A-beta production caused by metformin was not due to increased APP expression, because the total APP level was unaltered.
Formal Description
Interaction-ID: 3266

drug/chemical compound

Metformin

NOT affects_expression of

gene/protein

APP

Drugbank entries Show/Hide entries for Metformin or APP
Comment The increased A-beta production caused by metformin was not due to increased APP expression, because the total APP level was unaltered.
Formal Description
Interaction-ID: 3268

drug/chemical compound

Metformin

affects_quantity of

gene/protein

APP

Drugbank entries Show/Hide entries for Metformin or APP
Comment Metformins effect on A-beta production is mediated by activation of the AMP kinase (AMPK) in vitro and in vivo. E.g. in wild-type C57B6 mice treated with metformin for 6 days AMPK/ACC and BACE1 showed increased activity in the brains (frontal region).
Formal Description
Interaction-ID: 3274

drug/chemical compound

Metformin

increases_activity of

complex/PPI

AMPK

in vitro and in vivo
Drugbank entries Show/Hide entries for Metformin
Comment In wild-type C57B6 mice treated with metformin for 6 days AMPK/ACC and BACE1 showed increased activity in the brains (frontal region).
Formal Description
Interaction-ID: 3295

drug/chemical compound

Metformin

increases_activity of

gene/protein

ACACA

in brain frontal region; in wild-type C57B6 mice; in vivo
Drugbank entries Show/Hide entries for Metformin or ACACA
Comment In wild-type C57B6 mice treated with metformin for 6 days AMPK/ACC and BACE1 showed increased activity in the brains (frontal region).
Formal Description
Interaction-ID: 3296

drug/chemical compound

Metformin

increases_activity of

gene/protein

BACE1

in brain frontal region; in wild-type C57B6 mice; in vivo
Drugbank entries Show/Hide entries for Metformin or BACE1
Comment Intracellular beta-amyloid peptides were reduced in the presence of 1 microM, but not 0.25 microM, insulin.
Formal Description
Interaction-ID: 3297

complex/PPI

Insulin

affects_quantity of

gene/protein

Amyloid beta peptide

in the cell; depending on insulin concentration
Comment Metformin potentiated insulin's beta-amyloid lowering effect, with a significant inhibition of intracellular beta-amyloid peptides at 0.25 microM insulin, when both insulin and metformin were present.
Formal Description
Interaction-ID: 3298

drug/chemical compound

Metformin

increases_activity of

complex/PPI

Insulin

insulin's beta-amyloid lowering effect
Drugbank entries Show/Hide entries for Metformin
Comment Inhibition of AMP-activated protein kinase (AMPK) by the pharmacological inhibitor Compound C largely suppresses metformin's effect on beta-amyloid generation and BACE1 transcription, suggesting an AMPK-dependent mechanism.
Formal Description
Interaction-ID: 3303

drug/chemical compound

Compound C

decreases_activity of

complex/PPI

AMPK

Comment The antidiabetic drug metformin (Glucophage) increases biogenesis of Alzheimer's amyloid peptides via up-regulating BACE1 transcription, which raises the concern of possible side-effects, of accelerating Alzheimer's disease clinical manifestation in elderly patients with type 2 diabetes.
Formal Description
Interaction-ID: 3304

drug/chemical compound

Metformin

affects_activity of

via BACE1 expression
Drugbank entries Show/Hide entries for Metformin
Comment Inhibition of AMP-activated protein kinase (AMPK) by the pharmacological inhibitor Compound C largely suppresses metformin's effect on beta-amyloid generation and BACE1 transcription, suggesting an AMPK-dependent mechanism.
Formal Description
Interaction-ID: 12924

drug/chemical compound

Compound C

affects_activity of

drug/chemical compound

Metformin

via AMPK
Drugbank entries Show/Hide entries for