General Information:

Id: 462
Diseases: Diabetes mellitus, type II - [OMIM]
Fatty liver disease, nonalcoholic
Insulin resistance
Mus musculus
male
short-term overexpression of AMPK specifically in the liver by adenovirus-mediated transfer of a gene encoding a constitutively active form of AMPKalpha2 (AMPKalpha2-CA)
article
Reference: Foretz M et al.(2005) Short-term overexpression of a constitutively active form of AMP-activated protein kinase in the liver leads to mild hypoglycemia and fatty liver. Diabetes 54: 1331-1339 [PMID: 15855317]

Interaction Information:

Comment The effect of a short-term overexpression of AMPK specifically in the liver by adenovirus-mediated transfer of a gene encoding a constitutively active form of AMPKalpha2 (AMPKalpha2-CA) was investigated. Hepatic AMPKalpha2-CA expression significantly decreased blood glucose levels and gluconeogenic gene expression (PEPCK and G6Pase).
Formal Description
Interaction-ID: 2089

complex/PPI

AMPK

affects_activity of

process

gluconeogenesis

Comment In normal mouse liver, AMPKalpha2-CA considerably decreased the refeeding-induced transcriptional activation of genes encoding proteins involved in glycolysis and lipogenesis and their upstream regulators, SREBP-1 (sterol regulatory element-binding protein-1) and ChREBP (carbohydrate response element-binding protein). This resulted in decreases in hepatic glycogen synthesis and circulating lipid levels. Surprisingly, despite the inhibition of hepatic lipogenesis, expression of AMPKalpha2-CA led to fatty liver due to the accumulation of lipids released from adipose tissue.
Formal Description
Interaction-ID: 2093

gene/protein

PRKAA2

decreases_activity of

Comment The relative scarcity of glucose due to AMPKalpha2-CA expression led to an increase in hepatic fatty acid oxidation and ketone bodies production as an alternative source of energy for peripheral tissues. Thus, short-term AMPK activation in the liver reduces blood glucose levels and results in a switch from glucose to fatty acid utilization to supply energy needs.
Formal Description
Interaction-ID: 2094

gene/protein

PRKAA2

increases_activity of

Comment Ad AMPKalpha2-CA injection triggered a decrease in plasma glucose concentration in the fasted and fed states, 24 and 48 h after infection. This effect on blood glucose levels was associated with a physiological response of the pancreatic hormones, a decrease in plasma insulin, and an increase in plasma glucagon concentrations.
Formal Description
Interaction-ID: 2095

gene/protein

PRKAA2

decreases_quantity of

complex/PPI

Insulin

in blood
Comment The activation of SREBP-1 and ChREBP was considerably reduced in refed AMPKalpha2-CA infected mice. This resulted in a lower level of transcriptional activation of downstream target genes, including the genes encoding GLUT2, GK, L-PK, ACC1, ACC2, FAS, S14, and GPAT in response to refeeding.
Formal Description
Interaction-ID: 2096

gene/protein

PRKAA2

affects_expression of

gene/protein

SLC2A2

in response to refeeding, via SREBP-1 and ChREBP
Drugbank entries Show/Hide entries for SLC2A2
Comment The genes encoding the LDLr and HMG-CoA synthase, involved in cholesterol uptake and synthesis, were downregulated in fasted and refed AMPKalpha2-CA infected mice.
Formal Description
Interaction-ID: 2097

gene/protein

PRKAA2

decreases_expression of

gene/protein

LDLR

Drugbank entries Show/Hide entries for LDLR
Comment The abundance of HKII and GAPDH mRNAs was higher in fasted and refed AMPKalpha2-CA animals.
Formal Description
Interaction-ID: 2100

gene/protein

PRKAA2

increases_expression of

gene/protein

HK2

Comment The effect of a short-term overexpression of AMPK specifically in the liver by adenovirus-mediated transfer of a gene encoding a constitutively active form of AMPKalpha2 (AMPKalpha2-CA) was investigated. Hepatic AMPKalpha2-CA expression significantly decreased blood glucose levels and gluconeogenic gene expression (PEPCK and G6Pase).
Formal Description
Interaction-ID: 12364

complex/PPI

AMPK

affects_expression of

gene/protein

PCK1

Drugbank entries Show/Hide entries for PCK1
Comment The effect of a short-term overexpression of AMPK specifically in the liver by adenovirus-mediated transfer of a gene encoding a constitutively active form of AMPKalpha2 (AMPKalpha2-CA) was investigated. Hepatic AMPKalpha2-CA expression significantly decreased blood glucose levels and gluconeogenic gene expression (PEPCK and G6Pase).
Formal Description
Interaction-ID: 12365

complex/PPI

AMPK

affects_expression of

gene/protein

G6PC

Comment The effect of a short-term overexpression of AMPK specifically in the liver by adenovirus-mediated transfer of a gene encoding a constitutively active form of AMPKalpha2 (AMPKalpha2-CA) was investigated. Hepatic AMPKalpha2-CA expression significantly decreased blood glucose levels and gluconeogenic gene expression (PEPCK and G6Pase).
Formal Description
Interaction-ID: 12366

complex/PPI

AMPK

affects_quantity of

drug/chemical compound

Glucose

in blood
Comment In normal mouse liver, AMPKalpha2-CA considerably decreased the refeeding-induced transcriptional activation of genes encoding proteins involved in glycolysis and lipogenesis and their upstream regulators, SREBP-1 (sterol regulatory element-binding protein-1) and ChREBP (carbohydrate response element-binding protein). This resulted in decreases in hepatic glycogen synthesis and circulating lipid levels. Surprisingly, despite the inhibition of hepatic lipogenesis, expression of AMPKalpha2-CA led to fatty liver due to the accumulation of lipids released from adipose tissue.
Formal Description
Interaction-ID: 12367

gene/protein

PRKAA2

decreases_activity of

Comment In normal mouse liver, AMPKalpha2-CA considerably decreased the refeeding-induced transcriptional activation of genes encoding proteins involved in glycolysis and lipogenesis and their upstream regulators, SREBP-1 (sterol regulatory element-binding protein-1) and ChREBP (carbohydrate response element-binding protein). This resulted in decreases in hepatic glycogen synthesis and circulating lipid levels. Surprisingly, despite the inhibition of hepatic lipogenesis, expression of AMPKalpha2-CA led to fatty liver due to the accumulation of lipids released from adipose tissue.
Formal Description
Interaction-ID: 12368

gene/protein

PRKAA2

decreases_expression of

gene/protein

SREBF1

Comment In normal mouse liver, AMPKalpha2-CA considerably decreased the refeeding-induced transcriptional activation of genes encoding proteins involved in glycolysis and lipogenesis and their upstream regulators, SREBP-1 (sterol regulatory element-binding protein-1) and ChREBP (carbohydrate response element-binding protein). This resulted in decreases in hepatic glycogen synthesis and circulating lipid levels. Surprisingly, despite the inhibition of hepatic lipogenesis, expression of AMPKalpha2-CA led to fatty liver due to the accumulation of lipids released from adipose tissue.
Formal Description
Interaction-ID: 12369

gene/protein

PRKAA2

decreases_expression of

gene/protein

MLXIPL

Comment In normal mouse liver, AMPKalpha2-CA considerably decreased the refeeding-induced transcriptional activation of genes encoding proteins involved in glycolysis and lipogenesis and their upstream regulators, SREBP-1 (sterol regulatory element-binding protein-1) and ChREBP (carbohydrate response element-binding protein). This resulted in decreases in hepatic glycogen synthesis and circulating lipid levels. Surprisingly, despite the inhibition of hepatic lipogenesis, expression of AMPKalpha2-CA led to fatty liver due to the accumulation of lipids released from adipose tissue.
Formal Description
Interaction-ID: 12370

gene/protein

PRKAA2

decreases_activity of

in liver
Comment In normal mouse liver, AMPKalpha2-CA considerably decreased the refeeding-induced transcriptional activation of genes encoding proteins involved in glycolysis and lipogenesis and their upstream regulators, SREBP-1 (sterol regulatory element-binding protein-1) and ChREBP (carbohydrate response element-binding protein). This resulted in decreases in hepatic glycogen synthesis and circulating lipid levels. Surprisingly, despite the inhibition of hepatic lipogenesis, expression of AMPKalpha2-CA led to fatty liver due to the accumulation of lipids released from adipose tissue.
Formal Description
Interaction-ID: 12371

gene/protein

PRKAA2

increases_activity of

disease

Fatty liver disease, nonalcoholic

in liver
Comment The relative scarcity of glucose due to AMPKalpha2-CA expression led to an increase in hepatic fatty acid oxidation and ketone bodies production as an alternative source of energy for peripheral tissues. Thus, short-term AMPK activation in the liver reduces blood glucose levels and results in a switch from glucose to fatty acid utilization to supply energy needs.
Formal Description
Interaction-ID: 12372

gene/protein

PRKAA2

increases_activity of

Comment Ad AMPKalpha2-CA injection triggered a decrease in plasma glucose concentration in the fasted and fed states, 24 and 48 h after infection. This effect on blood glucose levels was associated with a physiological response of the pancreatic hormones, a decrease in plasma insulin, and an increase in plasma glucagon concentrations.
Formal Description
Interaction-ID: 12373

gene/protein

PRKAA2

increases_quantity of

gene/protein

Glucagon

in blood
Comment The activation of SREBP-1 and ChREBP was considerably reduced in refed AMPKalpha2-CA infected mice. This resulted in a lower level of transcriptional activation of downstream target genes, including the genes encoding GLUT2, GK, L-PK, ACC1, ACC2, FAS, S14, and GPAT in response to refeeding.
Formal Description
Interaction-ID: 12374

gene/protein

PRKAA2

affects_expression of

gene/protein

GCK

in response to refeeding, via SREBP-1 and ChREBP
Drugbank entries Show/Hide entries for GCK
Comment The activation of SREBP-1 and ChREBP was considerably reduced in refed AMPKalpha2-CA infected mice. This resulted in a lower level of transcriptional activation of downstream target genes, including the genes encoding GLUT2, GK, L-PK, ACC1, ACC2, FAS, S14, and GPAT in response to refeeding.
Formal Description
Interaction-ID: 12375

gene/protein

PRKAA2

affects_expression of

gene/protein

PKLR

in response to refeeding, via SREBP-1 and ChREBP
Drugbank entries Show/Hide entries for PKLR
Comment The activation of SREBP-1 and ChREBP was considerably reduced in refed AMPKalpha2-CA infected mice. This resulted in a lower level of transcriptional activation of downstream target genes, including the genes encoding GLUT2, GK, L-PK, ACC1, ACC2, FAS, S14, and GPAT in response to refeeding.
Formal Description
Interaction-ID: 12376

gene/protein

PRKAA2

affects_expression of

gene/protein

ACACA

in response to refeeding, via SREBP-1 and ChREBP
Drugbank entries Show/Hide entries for ACACA
Comment The activation of SREBP-1 and ChREBP was considerably reduced in refed AMPKalpha2-CA infected mice. This resulted in a lower level of transcriptional activation of downstream target genes, including the genes encoding GLUT2, GK, L-PK, ACC1, ACC2, FAS, S14, and GPAT in response to refeeding.
Formal Description
Interaction-ID: 12377

gene/protein

PRKAA2

affects_expression of

gene/protein

FASN

in response to refeeding, via SREBP-1 and ChREBP
Drugbank entries Show/Hide entries for FASN
Comment The activation of SREBP-1 and ChREBP was considerably reduced in refed AMPKalpha2-CA infected mice. This resulted in a lower level of transcriptional activation of downstream target genes, including the genes encoding GLUT2, GK, L-PK, ACC1, ACC2, FAS, S14, and GPAT in response to refeeding.
Formal Description
Interaction-ID: 12378

gene/protein

PRKAA2

affects_expression of

gene/protein

THRSP

in response to refeeding, via SREBP-1 and ChREBP
Comment The activation of SREBP-1 and ChREBP was considerably reduced in refed AMPKalpha2-CA infected mice. This resulted in a lower level of transcriptional activation of downstream target genes, including the genes encoding GLUT2, GK, L-PK, ACC1, ACC2, FAS, S14, and GPAT in response to refeeding.
Formal Description
Interaction-ID: 12379

gene/protein

PRKAA2

affects_expression of

gene/protein

GPAM

in response to refeeding, via SREBP-1 and ChREBP
Comment The genes encoding the LDLr and HMG-CoA synthase, involved in cholesterol uptake and synthesis, were downregulated in fasted and refed AMPKalpha2-CA infected mice.
Formal Description
Interaction-ID: 12380

gene/protein

PRKAA2

decreases_expression of

gene/protein

HMGCS2

Comment The genes encoding the LDLr and HMG-CoA synthase, involved in cholesterol uptake and synthesis, were downregulated in fasted and refed AMPKalpha2-CA infected mice.
Formal Description
Interaction-ID: 12381

gene/protein

PRKAA2

decreases_activity of

Comment The genes encoding the LDLr and HMG-CoA synthase, involved in cholesterol uptake and synthesis, were downregulated in fasted and refed AMPKalpha2-CA infected mice.
Formal Description
Interaction-ID: 12382

gene/protein

PRKAA2

decreases_activity of

Comment The abundance of HKII and GAPDH mRNAs was higher in fasted and refed AMPKalpha2-CA animals.
Formal Description
Interaction-ID: 12383

gene/protein

PRKAA2

increases_expression of

gene/protein

GAPDH

Drugbank entries Show/Hide entries for GAPDH
Comment The activation of SREBP-1 and ChREBP was considerably reduced in refed AMPKalpha2-CA infected mice. This resulted in a lower level of transcriptional activation of downstream target genes, including the genes encoding GLUT2, GK, L-PK, ACC1, ACC2, FAS, S14, and GPAT in response to refeeding.
Formal Description
Interaction-ID: 15040

gene/protein

PRKAA2

affects_expression of

gene/protein

ACACB

in response to refeeding, via SREBP-1 and ChREBP
Drugbank entries Show/Hide entries for ACACB