Selected AMPK and IGF-IR signalling pathways relevant to this study in normal (A) and hyperglycaemic (B) conditions

Overview of selected AMPK and IGF-IR signalling pathways relevant to this study in normal (A) and hyperglycaemic (B) conditions. In normal conditions, metformin activates AMPKThr172 through the LKB1 signalling pathway. Activated AMPK inhibits cell growth by repressing mTOR activity through activation of TSC2 and phosphorylation of inhibitory serine residues on IRS-1. In addition, as demonstrated in the present study, metformin suppresses IGF-IR activation and reduces IRS-1 levels, which disable further signalling through the PI3K/Akt pathway. During hyperglycaemia, signalling through the IGF-IR pathway appears more robust, leading to phosphorylation of Akt and AMPKSer485. This inhibitory Ser485 site can inhibit activation of AMPKThr172, possibly contributing to the impaired growth inhibitory effect by metformin at high glucose conditions.
Selected AMPK and IGF-IR signalling pathways relevant to this study in normal (A) and hyperglycaemic (B) conditions
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Publication

Metformin-mediated growth inhibition involves suppression of the IGF-I receptor signalling pathway in human pancreatic cancer cells. (2013) Emelie Karnevi, et al. BMC Cancer. 2013;13:235-235. Figure: F7.

Gene mentions


Organism Group Word Match Source NCBI Symbol NCBI ID
Gallus gallus Vertebrates IGF-I IGF-I ncbigene_symbol IGF-I 100309514
Gallus gallus Vertebrates IGF-I IGF-I ncbigene_symbol IGF-I 100327329
Gallus gallus Vertebrates IGF-I IGF-I ncbigene_symbol IGF-I 100327342
Gallus gallus Vertebrates IGF-I IGF-I ncbigene_symbol IGF-I 100327692
Gallus gallus Vertebrates IGF-I IGF-I ncbigene_symbol IGF-I 100327695
Gallus gallus Vertebrates IGF-I IGF-I ncbigene_symbol IGF-I 100327731
Gallus gallus Vertebrates IGF-I IGF-I ncbigene_symbol IGF-I 100327808
Gallus gallus Vertebrates IGF-I IGF-I ncbigene_symbol IGF-I 100327816
Gallus gallus Vertebrates IGF-I IGF-I ncbigene_symbol IGF-I 100327844
Gallus gallus Vertebrates IGF-I IGF-I ncbigene_synonym IGF1 418090
Gallus gallus Vertebrates LKB1 LKB1 ncbigene_synonym STK11 420105
Gallus gallus Vertebrates TSC2 TSC2 ncbigene_symbol TSC2 416552
Gallus gallus Vertebrates mTor MTOR ncbigene_symbol MTOR 419455
Homo sapiens Primates IGF-I IGF-I ncbigene_synonym IGF1 3479
Homo sapiens Primates IGF-IR IGFIR ncbigene_synonym IGF1R 3480
Homo sapiens Primates PI3K PI3K ncbigene_synonym PIK3CA 5290
Homo sapiens Primates PI3K PI3K ncbigene_synonym PIK3CB 5291
Homo sapiens Primates PI3K PI3K ncbigene_synonym PIK3CD 5293
Homo sapiens Primates PI3K PI3K ncbigene_synonym PIK3CG 5294
Homo sapiens Primates PI3K PI3K famplex_relations PIK3R3 8503
Homo sapiens Primates PI3K PI3K famplex_relations PIK3R4 30849
Homo sapiens Primates PI3K PI3K famplex_relations PIK3R5 23533
Homo sapiens Primates PI3K PI3K famplex_relations PIK3R6 146850
Homo sapiens Primates PI3K PI3K famplex_relations PIK3R1 5295
Homo sapiens Primates PI3K PI3K famplex_relations PIK3R2 5296
Homo sapiens Primates LKB1 LKB1 ncbigene_synonym STK11 6794
Homo sapiens Primates IRS-1 IRS1 ncbigene_symbol IRS1 3667
Homo sapiens Primates Akt AKT ncbigene_synonym AKT1 207
Homo sapiens Primates Akt AKT famplex_relations AKT2 208
Homo sapiens Primates Akt AKT famplex_relations AKT3 10000
Homo sapiens Primates AMPK AMPK ncbigene_synonym PRKAA1 5562
Homo sapiens Primates AMPK AMPK ncbigene_synonym PRKAA2 5563
Homo sapiens Primates AMPK AMPK ncbigene_synonym PRKAB1 5564
Homo sapiens Primates AMPK AMPK famplex_relations PRKAB2 5565
Homo sapiens Primates AMPK AMPK famplex_relations PRKAG1 5571
Homo sapiens Primates AMPK AMPK famplex_relations PRKAG2 51422
Homo sapiens Primates AMPK AMPK famplex_relations PRKAG3 53632
Homo sapiens Primates TSC2 TSC2 ncbigene_symbol TSC2 7249
Homo sapiens Primates mTor MTOR ncbigene_symbol MTOR 2475
Bos taurus Mammals IGF-I IGF-I ncbigene_synonym IGF1 281239
Bos taurus Mammals PI3K PI3K ncbigene_synonym PIK3CB 517948
Bos taurus Mammals IRS-1 IRS1 ncbigene_symbol IRS1 538598
Bos taurus Mammals Akt AKT ncbigene_synonym AKT1 280991
Bos taurus Mammals TSC2 TSC2 ncbigene_symbol TSC2 504985
Bos taurus Mammals mTor MTOR ncbigene_symbol MTOR 100139219
Drosophila melanogaster Invertebrates PI3K PI3K ncbigene_synonym Pi3K21B 33203
Drosophila melanogaster Invertebrates PI3K PI3K ncbigene_synonym Pi3K59F 37733
Drosophila melanogaster Invertebrates PI3K PI3K ncbigene_synonym Pi3K68D 39329
Drosophila melanogaster Invertebrates PI3K PI3K ncbigene_synonym Pi3K92E 42446
Drosophila melanogaster Invertebrates LKB1 LKB1 ncbigene_symbol Lkb1 41673
Drosophila melanogaster Invertebrates Akt AKT ncbigene_symbol Akt 41957
Drosophila melanogaster Invertebrates AMPK AMPK ncbigene_synonym SNF4Agamma 42515
Drosophila melanogaster Invertebrates AMPK AMPK ncbigene_synonym AMPKalpha 43904
Drosophila melanogaster Invertebrates TSC2 TSC2 ncbigene_synonym gig 40201
Drosophila melanogaster Invertebrates mTor MTOR ncbigene_symbol Mtor 36264
Drosophila melanogaster Invertebrates mTor MTOR ncbigene_synonym Tor 47396
Danio rerio Vertebrates IGF-I IGF-I ncbigene_synonym igf1 114433
Danio rerio Vertebrates IGF-IR IGF-IR ncbigene_synonym igf1rb 245702
Danio rerio Vertebrates IRS-1 IRS1 ncbigene_symbol irs1 559281
Danio rerio Vertebrates TSC2 TSC2 ncbigene_symbol tsc2 567524
Danio rerio Vertebrates mTor MTOR ncbigene_symbol mtor 324254

Chemical mentions

Word Match MeSH Name ChEBI
Glucose Glucose mesh:D005947 D-glucopyranose chebi:4167
Metformin Metformin mesh:D008687 metformin chebi:6801

Disease mentions

Word Match MeSH Name DOID