Elusive liver factor that causes pancreatic α cell hyperplasia: A review of literature

Table 1 Genes significantly overexpressed in the Gcgr^-/- mouse liver

Gene symbol	mRNA description	GO biological process term	Fold increase
Cdkn1a	Cyclin-dependent kinase inhibitor 1A (P21), transcript variant 1	Response to DNA damage stimulus/cell cycle/cell cycle arrest/negative regulation of cell proliferation	5.6
Igfbp1	Insulin-like growth factor binding protein 1	Regulation of cell growth	5.5
Defb1	Defensin beta 1	Defense response/response to bacterium/defense response to bacterium/innate immune response	5.2
Gpr64	G protein-coupled receptor 64, transcript variant 1	Signal transduction/cell surface receptor linked signaling pathway/G-protein coupled receptor protein signaling pathway/neuropeptide signaling pathway	5.1
Serpina7	Serine (or cysteine) peptidase inhibitor, clade A (alpha-1 antiproteinase, antitrypsin), member 7	Post-embryonic development/response to vitamin A/response to drug	4.9
Cpt1b	Carnitine palmitoyltransferase 1b, muscle, nuclear gene encoding mitochondrial protein	Lipid metabolic process/fatty acid metabolic process/transport/long-chain fatty acid transport/long-chain fatty acid transport	4.6
Chac1	ChaC, cation transport regulator-like 1 (E. coli)	Apoptosis/response to unfolded protein/biological_process	4.3
Npas2	Neuronal PAS domain protein 2	Transcription/regulation of transcription, DNA-dependent/signal transduction/circadian sleep/wake cycle/regulation of transcription/locomotor rhythm/positive regulation of transcription from RNA polymerase II promoter/rhythmic process	3.9
Slc34a2	Solute carrier family 34 (sodium phosphate), member 2	In utero embryonic development/transport/ion transport/sodium ion transport/phosphate transport/phosphate transport/phosphate transport	3.6
Fabp5	Fatty acid binding protein 5, epidermal	Glucose metabolic process/lipid metabolic process/phosphatidylcholine biosynthetic process/transport/glucose transport	3.5
BC023105	cDNA sequence BC023105	Unknown	3.1
Cav1	Caveolin 1, caveolae protein	MAPKKK cascade/inactivation of MAPK activity/vasculogenesis/response to hypoxia/negative regulation of endothelial cell proliferation/negative regulation of cytokine-mediated signaling pathway/triglyceride metabolic process/calcium ion transport/cellular calcium ion homeostasis/cellular calcium ion homeostasis/endocytosis/regulation of smooth muscle contraction	2.8
Lpl	Lipoprotein lipase	Lipid metabolic process/positive regulation of macrophage derived foam cell differentiation/lipid catabolic process/triglyceride biosynthetic process/triglyceride catabolic process	2.7
Il22ra1	Interleukin 22 receptor, alpha 1	Blood coagulation	2.6
Acaca	Acetyl-Coenzyme A carboxylase alpha	Tissue homeostasis/acetyl-CoA metabolic process/lipid metabolic process/fatty acid biosynthetic process/metabolic process/lipid biosynthetic process/response to organic cyclic substance/multicellular organismal protein metabolic process	2.6
Inhba	Inhibin beta-A	Mesoderm formation/hemopoietic progenitor cell differentiation/growth/positive regulation of transcription from RNA polymerase II promoter/mesodermal cell differentiation/negative regulation of hair follicle development	2.6
Gadd45b	Growth arrest and DNA-damage-inducible 45 beta	Activation of MAPKK activity/negative regulation of protein kinase activity/apoptosis/multicellular organismal development/cell differentiation/regulation of cell cycle	2.4
Tgtp1	T-cell specific GTPase 1	Immune response/response to virus	2.4
Rassf4	Ras association (RalGDS/AF-6) domain family member 4	Cell cycle/signal transduction	2.4
Cxcl13	Chemokine (C-X-C motif) ligand 13	Chemotaxis/inflammatory response/immune response/lymph node development	2.4
Il1b	Interleukin 1 beta	Angiogenesis/fever/inflammatory response/immune response/elevation of cytosolic calcium ion concentration/aging	2.4
Tgtp1	T-cell specific GTPase 1	Immune response/response to virus	2.3
Asns	Asparagine synthetase	Asparagine biosynthetic process/glutamine metabolic process/metabolic process/cellular amino acid biosynthetic process	2.3
Socs2	Suppressor of cytokine signaling 2, transcript variant 1	Lactation/regulation of growth/regulation of multicellular organism growth/negative regulation of multicellular organism growth/negative regulation of multicellular organism growth/positive regulation of neuron differentiation/negative regulation of JAK-STAT cascade/mammary gland alveolus development	2.3
Meig1	Meiosis expressed gene 1	Meiosis	2.3
Cxcl9	Chemokine (C-X-C motif) ligand 9	Inflammatory response/immune response	2.2
Vtcn1	V-set domain containing T cell activation inhibitor 1	Negative regulation of T cell activation	2.2
H2-Ab1	Histocompatibility 2, class II antigen A, beta 1	Antigen processing and presentation of peptide or polysaccharide antigen via MHC class II/immune response/antigen processing and presentation/antigen processing and presentation of exogenous peptide antigen via MHC class II	2.2
Spon2	Spondin 2, extracellular matrix protein	Cell adhesion/innate immune response	2.2
Rgs16	Regulator of G-protein signaling 16	G-protein coupled receptor protein signaling pathway/negative regulation of signal transduction	2.1
Il2rg	Interleukin 2 receptor, gamma chain	Regulation of gene expression/positive regulation of CD4-positive, CD25-positive, alpha-beta regulatory T cell differentiation/positive regulation of T cell differentiation in the thymus/positive regulation of B cell differentiation	2.1
Wdr67	WD repeat domain 67, transcript variant 1	Regulation of Rab GTPase activity	2.1
Prss8	Protease, serine, 8 (prostasin)	Hair follicle development/proteolysis	2.1
Bach2	BTB and CNC homology 2	Transcription/regulation of transcription, DNA-dependent/regulation of transcription	2.0
Serpina12	Serine (or cysteine) peptidase inhibitor, clade A (alpha-1 antiproteinase, antitrypsin), member 12	Unknown	2.0

E. coli: Escherichia coli.

Table 2 Genes significantly underexpressed in the Gcgr^-/- mouse liver

Gene symbol	mRNA description	GO biological process term	Fold decrease
Mmd2	Monocyte to macrophage differentiation-associated 2	Cytolysis	9.7
Nnmt	Nicotinamide N-methyltransferase	Unknown	6.2
Gcgr	Glucagon receptor	Exocytosis/signal transduction/cell surface receptor linked signaling pathway/G-protein coupled receptor protein signaling pathway/G-protein signaling, coupled to cAMP nucleotide second messenger/activation of adenylate cyclase activity by G-protein signaling pathway	5.3
Mfsd2a	Major facilitator superfamily domain containing 2A	Transport/transmembrane transport	4.2
Oat	Ornithine aminotransferase, nuclear gene encoding mitochondrial protein	Unknown	4.1
Slc10a2	Solute carrier family 10, member 2	Transport/ion transport/sodium ion transport/organic anion transport/bile acid and bile salt transport	3.9
A1bg	Alpha-1-B glycoprotein	Unknown	3.5
Gm129	Gene model 129 (NCBI)	Unknown	3.3
Sds	Serine dehydratase	Gluconeogenesis/cellular amino acid metabolic process/metabolic process	3.1
Pck1	Phosphoenolpyruvate carboxykinase 1, cytosolic	Gluconeogenesis/gluconeogenesis/oxaloacetate metabolic process/lipid metabolic process/glycerol biosynthetic process from pyruvate	3.0
Lrtm1	Leucine-rich repeats and transmembrane domains 1	Unknown	3.0
Ntrk2	Neurotrophic tyrosine kinase, receptor, type 2, transcript variant 1	Vasculogenesis/protein amino acid phosphorylation/transmembrane receptor protein tyrosine kinase signaling pathway/multicellular organismal development/nervous system development/feeding behavior/glutamate secretion/regulation of metabolic process/cell differentiation/brain-derived neurotrophic factor receptor signaling pathway/mechanoreceptor differentiation	3.0
Gls2	Glutaminase 2 (liver, mitochondrial), nuclear gene encoding mitochondrial protein	Gutamine metabolic process	3.0
Susd4	Sushi domain containing 4	Unknown	2.9
Slc16a5	Solute carrier family 16 (monocarboxylic acid transporters), member 5	Unknown	2.9
Ccrn4l	CCR4 carbon catabolite repression 4-like (S. cerevisiae)	Rhythmic process	2.9
Lhpp	Phospholysine phosphohistidine inorganic pyrophosphate phosphatase	Metabolic process	2.7
Neb	Nebulin	Regulation of actin filament length/sarcomere organization	2.6
Got1	Glutamate oxaloacetate transaminase 1, soluble	Oxaloacetate metabolic process/glycerol biosynthetic process/cellular amino acid metabolic process/aspartate metabolic process/aspartate biosynthetic process/biosynthetic process/glutamate catabolic process to aspartate/glutamate catabolic process to 2-oxoglutarate/dicarboxylic acid metabolic process/fatty acid homeostasis	2.6
Sult5a1	Sulfotransferase family 5A, member 1	Unknown	2.6
Hapln1	Hyaluronan and proteoglycan link protein 1	Cell adhesion	2.5
Mt2	Metallothionein 2	Cellular zinc ion homeostasis/nitric oxide mediated signal transduction/detoxification of copper ion	2.5
Mt1	Metallothionein 1	Cellular metal ion homeostasis/cellular zinc ion homeostasis/nitric oxide mediated signal transduction/detoxification of copper ion	2.4
Slc3a1	Solute carrier family 3, member 1	Amino acid transport	2.4
Trdn	Triadin	Cellular calcium ion homeostasis/regulation of release of sequestered calcium ion into cytosol by sarcoplasmic reticulum/negative regulation of calcium ion transport via store-operated calcium channel activity	2.4
Bhlhe41	Basic helix-loop-helix family, member e41	Negative regulation of transcription from RNA polymerase II promoter/transcription/regulation of transcription, DNA-dependent/circadian rhythm/entrainment of circadian clock/regulation of transcription	2.3
Usp2	Ubiquitin specific peptidase 2, transcript variant 3	Ubiquitin-dependent protein catabolic process	2.3
Derl3	Der1-like domain family, member 3	Unknown	2.3
Mrap2	Melanocortin 2 receptor accessory protein 2, transcript variant 1	Unknown	2.2
Ncam2	Neural cell adhesion molecule 2, transcript variant 1	Cell adhesion	2.2
S1pr5	Sphingosine-1-phosphate receptor 5	Signal transduction/G-protein coupled receptor protein signaling pathway	2.2
1810046K07Rik	RIKEN cDNA 1810046K07 gene	Unknown	2.2
Nrg4	Neuregulin 4	Unknown	2.2
Gas2	Growth arrest specific 2	Apoptosis/cell cycle/cell cycle arrest/regulation of cell shape	2.2
Ttc39b	Tetratricopeptide repeat domain 39B	Unknown	2.2
Cyp17a1	Cytochrome P450, family 17, subfamily a, polypeptide 1	Steroid biosynthetic process/glucocorticoid biosynthetic process/oxidation reduction	2.1
Creld2	cysteine-rich with EGF-like domains 2	Unknown	2.1
Upp2	Uridine phosphorylase 2	Nucleoside metabolic process/nucleotide catabolic process	2.1
Ar	Androgen receptor	In utero embryonic development/transcription/regulation of transcription, DNA-dependent/regulation of transcription from RNA polymerase II promoter/male gonad development/cellular process/regulation of gene expression/male somatic sex determination/androgen receptor signaling pathway/androgen receptor signaling pathway/positive regulation of estrogen receptor signaling pathway/positive regulation of MAPKKK cascade/positive regulation of insulin-like growth factor receptor signaling pathway	2.1
Gm10419	Lung RCB-0558 LLC cDNA, RIKEN full-length enriched library, clone:G730014J15 product: Hypothetical protein	Unknown	2.1
Sdf2l1	Stromal cell-derived factor 2-like 1	Unknown	2.0
Trdn	Triadin	Cellular calcium ion homeostasis/regulation of release of sequestered calcium ion into cytosol by sarcoplasmic reticulum/negative regulation of calcium ion transport via store-operated calcium channel activity	2.0
Antxr2	Anthrax toxin receptor 2	Unknown	2.0

S. cerevisiae: Saccharomyces cerevisiae.

Table 3 Pathway analysis of differentially expressed genes in the Gcgr^-/- mouse liver

	Glucose homeostasis	Inflammation	Cell proliferation	Metabolism
Underexpressed in Gcgr-/- mouse liver	Nnmt, Got1, Sds, Pck1		Gas2	Slc10a2, Ntrk2, Gls2, Lhpp, Sult5a1, Mt2, Mt1, Slc3a1, Trdn, Usp2, Cyp17a1, Upp2
Overexpressed in Gcgr-/- mouse liver		Il1b, Cxcl13, Tgtp1, Cxcl9, Defb1, Vtcn1, H2-Ab1, Spon2, Il2rg	Cdkn1a, Igfbp1, Chac1, Cav1, Inhba, Gadd45b, Rassf4, Socs2, Meig1	Serpina7, Cpt1b, Slc34a2, Fabp5, Lpl, Acaca, Asns