General Information:

Id: 346
Diseases: Diabetes mellitus, type II - [OMIM]
Fatty liver disease, nonalcoholic
Insulin resistance
Rattus norvegicus
BTO:0000759 liver
article
Reference: Zhou G et al.(2001) Role of AMP-activated protein kinase in mechanism of metformin action J. Clin. Invest. 108: 1167-1174 [PMID: 11602624]

Interaction Information:

Comment Metformin promotes AMPK activation in primary rat hepatocytes.
Formal Description
Interaction-ID: 1396

drug/chemical compound

Metformin

increases_activity of

complex/PPI

AMPK

in liver; via phosphorylation of Thr172 of AMPK alpha chain
Drugbank entries Show/Hide entries for Metformin
Comment Both metformin and AICAR treatment induced AMPK Thr172 phosphorylation.
Formal Description
Interaction-ID: 1398

drug/chemical compound

Metformin

increases_phosphorylation of

complex/PPI

AMPK

in liver; at Thr172 of AMPK alpha chain
Drugbank entries Show/Hide entries for Metformin
Comment Both metformin and AICAR treatment induced AMPK Thr172 phosphorylation.
Formal Description
Interaction-ID: 1400

drug/chemical compound

AICAR

increases_phosphorylation of

complex/PPI

AMPK

in liver; at Thr172 of AMPK alpha chain
Drugbank entries Show/Hide entries for AICAR
Comment Metformin induces ACC inactivation in primary hepatocytes.
Formal Description
Interaction-ID: 1406

drug/chemical compound

Metformin

decreases_activity of

gene/protein

ACACA

in liver
Drugbank entries Show/Hide entries for Metformin or ACACA
Comment Both AICAR and metformin treatment stimulated fatty acid oxidation in isolated rat hepatocytes.
Formal Description
Interaction-ID: 1408

drug/chemical compound

AICAR

increases_activity of

in liver
Drugbank entries Show/Hide entries for AICAR
Comment Both AICAR and metformin treatment stimulated fatty acid oxidation in isolated rat hepatocytes.
Formal Description
Interaction-ID: 1410

drug/chemical compound

Metformin

increases_activity of

in liver
Drugbank entries Show/Hide entries for Metformin
Comment Increasing concentrations of metformin resulted in progressive inhibition of glucose-induced expression of FAS and S14 in hepatocytes.
Formal Description
Interaction-ID: 1435

drug/chemical compound

Metformin

decreases_expression of

gene/protein

FASN

in liver
Drugbank entries Show/Hide entries for Metformin or FASN
Comment Increasing concentrations of metformin resulted in progressive inhibition of glucose-induced expression of FAS and S14 in hepatocytes.
Formal Description
Interaction-ID: 1436

drug/chemical compound

Metformin

decreases_expression of

gene/protein

THRSP

in liver
Drugbank entries Show/Hide entries for Metformin
Comment Expression of HMG-CoA reductase was not affected by metformin.
Formal Description
Interaction-ID: 1437

drug/chemical compound

Metformin

NOT affects_activity of

gene/protein

HMGCR

in liver
Drugbank entries Show/Hide entries for Metformin or HMGCR
Comment Compound C is a potent reversible inhibitor of AMPK. Both metformin and AICAR were able to inhibit cumulative glucose production in primary cultured rat hepatocytes stimulated with glucagon. Coincubation of hepatocytes with compound C was able to attenuate the effects of metformin to decrease glucose production in these cells, demostrating that AMPK activation was required for metfomin's inhibitory effect on hepatocyte glucose production.
Formal Description
Interaction-ID: 1442

drug/chemical compound

Metformin

decreases_activity of

process

hepatic glucose production

in liver; via AMPK activation
Drugbank entries Show/Hide entries for Metformin
Comment Metformin-induced activation of AMPK in rat hepatocytes leads to decreased mRNA expression of SREBP-1c.
Formal Description
Interaction-ID: 1464

complex/PPI

AMPK

decreases_expression of

mRNA/protein variant

SREBF1c

in liver
Comment In vivo effects of metformin were examined in rats starved for 20 hours and then re-fed for 2 hours. Along with modest decreases in plasma insulin and triglycerides, a small, but significant increase in beta-hydroxybutyrate was present, suggesting that hepatic fatty acid oxidation was induced in metformin-treatet rats. Furthermore, metformin treatment produced significant decreases in hepatic expression of mRNAs for SREBP-1, FAS and S14 that were consistent with effects documented in cells.
Formal Description
Interaction-ID: 1466

drug/chemical compound

Metformin

increases_quantity of

drug/chemical compound

(R)-3-Hydroxybutanoate

in liver
Drugbank entries Show/Hide entries for Metformin
Comment In vivo effects of metformin were examined in rats starved for 20 hours and then re-fed for 2 hours. Along with modest decreases in plasma insulin and triglycerides, a small, but significant increase in beta-hydroxybutyrate was present, suggesting that hepatic fatty acid oxidation was induced in metformin-treatet rats. Furthermore, metformin treatment produced significant decreases in hepatic expression of mRNAs for SREBP-1, FAS and S14 that were consistent with effects documented in cells.
Formal Description
Interaction-ID: 12346

drug/chemical compound

Metformin

decreases_expression of

gene/protein

SREBF1

in liver
Drugbank entries Show/Hide entries for Metformin
Comment In vivo effects of metformin were examined in rats starved for 20 hours and then re-fed for 2 hours. Along with modest decreases in plasma insulin and triglycerides, a small, but significant increase in beta-hydroxybutyrate was present, suggesting that hepatic fatty acid oxidation was induced in metformin-treatet rats. Furthermore, metformin treatment produced significant decreases in hepatic expression of mRNAs for SREBP-1, FAS and S14 that were consistent with effects documented in cells.
Formal Description
Interaction-ID: 12347

drug/chemical compound

Metformin

decreases_expression of

gene/protein

FASN

in liver
Drugbank entries Show/Hide entries for Metformin or FASN
Comment In vivo effects of metformin were examined in rats starved for 20 hours and then re-fed for 2 hours. Along with modest decreases in plasma insulin and triglycerides, a small, but significant increase in beta-hydroxybutyrate was present, suggesting that hepatic fatty acid oxidation was induced in metformin-treatet rats. Furthermore, metformin treatment produced significant decreases in hepatic expression of mRNAs for SREBP-1, FAS and S14 that were consistent with effects documented in cells.
Formal Description
Interaction-ID: 12348

drug/chemical compound

Metformin

decreases_expression of

gene/protein

THRSP

in liver
Drugbank entries Show/Hide entries for Metformin