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Excess adiposity is the most important risk in the development of insulin resistance and type 2 diabetes mellitus (T2DM). Adipose tissue produces several proteins (adipocytokines) such as leptin, adiponectin, resistin, tumor necrosis factor-?, and IL-6, that modulate insulin sensitivity and appear to play an important role in the pathogenesis of insulin resistance, diabetes, dyslipidemia, inflammation, and atherosclerosis. However, the mechanisms by which fat tissue induces insulin resistance and the role of adipocytokines in the pathogenesis of T2DM have not been well established.
Visfatin, also known as pre-B cell colony-enhancing factor (PBEF), is a cytokine that is highly expressed in visceral fat and was originally isolated as a secreted factor that synergizes with IL-7 and stem cell factors to promote the growth of B cell precursors. Visfatin homologs have been identified in carp, invertebrate mollusks, and bacteria, as well as in vertebrates, including humans and the mouse. It has been postulated to play a role in innate immunity.
Visfatin exerts insulin-mimetic effects that are dose-dependent and quantitatively similar to those of insulin in stimulating muscle and adipocyte glucose transport, and in inhibiting hepatocyte glucose production. Intravenous injection of recombinant visfatin in mice decreased plasma glucose in a dose-dependent fashion. In keeping with its insulin-mimetic effects, visfatin was as effective as insulin in reducing hyperglycemia in insulin-deficient diabetic mice. Visfatin was also found to be bound to and activate insulin receptor, causing receptor phosphorylation and the activation of downstream signaling molecules. However, visfatin and insulin did not compete for binding to the insulin receptor, indicating that the two proteins were recognized by different regions of the receptor. Thus, visfatin might play a role in glucose homeostasis and dysregulation in biosynthesis or signal transduction, and might contribute to the pathogenesis of diabetes.

Folate Receptor 1, also known as FOLR1, is a part of the folate receptor family whose members bind folic acid. FOLR1 binds to folate and reduced folic acid derivatives and facilitates transfer of 5-methyltetrahydrofolate and folate analogs into the cells. FOLR1 is either attaches to membranes through a glycosyl-phosphatidylinositol linkage or exists in a soluble form. FOLR1 is also needed for embryonic development and normal cell proliferation.

A 16-kDa peptide hormone secreted from white adipocytes and implicated in the regulation of food intake and energy balance. Leptin provides the key afferent signal from fat cells in the feedback system that controls body fat stores.

"Epiregulin is part of the EGF family. Epiregulin functions as a ligand of EGFR, as well as a ligand of most members of the ERBB (v-erb-b2 oncogene homolog) family of tyrosine-kinase receptors.Epiregulin is expressed mostly in the placenta and peripheral blood leukocytes and in specific carcinomas of the bladder, lung, kidney and colon. Epiregulin stimulates the proliferation of keratinocytes, hepatocytes, fibroblasts and vascular smooth muscle cells. Epiregulin inhibits the growth of several tumor-derived epithelial cell lines. Human Epiregulin is initially synthesized as a glycosylated 19.0 kDa transmembrane precursor protein, which is processed by proteolytic cleavage to produce a 6.0 kDa mature secreted sequence."

NELL2 is expressed in large quantities in neural tissues and has a significant role in the development of neural tissues. In addition, NELL protein has six epidermal growth factor (EGF)-like repeat domains which plays a part in calcium binding.

PGK1 is an X-linked enzyme that has a major role in the glycolytic pathway. PGK1 is a glycolytic enzyme which catalyzes the conversion of 1,3-diphosphoglycerate to 3-phosphoglycerate, generating an ATP molecule. PGK1 may also act as a cofactor for polymerase alpha. Defects in the PGK1 gene are usually associated with chronic hemolytic anemia, though it can be accompanied by either mental retardation or muscular disease (rhabdomyolysis). Overexpression of PGK1 and its signalling targets are possibly an expression-pathway in diffuse primary gastric carcinomas promoting peritoneal dissemination. It was shown that PGK1 is differentially expressed in the dorsolateral prefrontal cortex from patients with schizophrenia.

TNFR1 belongs to the TNF-receptor superfamily. TNFR1 is a receptor for TNFSF2/TNF-alpha and homotrimeric TNFSF1/lymphotoxin-alpha.
There are 2 types of soluble TNF receptors: sTNFR-I and sTNFR-II, which act to neutralize the biological activities of TNF alpha and TNF beta. The levels of these soluble receptors seem to increase as a result of shedding of the extracellular domains of the membrane bound receptors. TNF-a, TNFR1 and TNFR2 have roles in cellular differentiation. TNFR1 and TNFR2 function in cell type-specific renal injury.
TNFR1 is capable of signaling both cell survival and apoptosis. TNFR1-induced apoptosis requires 2 sequential signaling complexes. TNFR1 is capable of activating NF-kappaB, mediate apoptosis, and function as a regulator of inflammation. Oxidative stress promotes TNFR1 and TNFR2 self-interaction, ligand-independent and enhanced ligand-dependent TNF signaling. TNFR1 contributes to the induction of non-cytocidal TNF effects including anti-viral state and activation of the acid sphingomyelinase. Human TNFR1 has a major region which controls cell surface expression. High levels of soluble TNF receptors are found in the amniotic fluid of pregnant women.
Germline mutations of the extracellular domains of TNFR1 are linked to the autosomal dominant periodic fever syndrome. The impaired receptor clearance is believed to be a mechanism of the disease. Familial hibernian fever (FHF) is caused by defects in TNFRSF1A gene.

Chemokine (C-X-C motif) ligand (CXCL7) is a small cytokine belonging to the CXC chemokine family. It is a protein that is released in large amounts from platelets following their activation. It stimulates various processes including mitogenesis, synthesis of extracellular matrix, glucose metabolism and synthesis of plasminogen activator.

Limb Bud And Heart Development, (LBH) belongs to the LBH family.LBH is highly expressed in the heart, and expressed at low levels in placenta, lung, skeletal muscle, kidney and liver. In addition, LBH protein is a transcriptional activator which may act in mitogen-activated protein kinase signaling pathway. Among the diseases associated with LBH are celiac disease, and rheumatoid arthritis.

Chemokine (C-X-C motif) ligand 2 (CXCL2) is a small cytokine belonging to the CXC chemokine family that is also called macrophage inflammatory protein 2-alpha (MIP2-alpha), Growth-regulated protein beta (Gro-beta) and Gro oncogene-2 (Gro-2). CXCL2 is 90% identical in amino acid sequence as a related chemokine, CXCL1. This chemokine is secreted by monocytes and macrophages and is chemotactic for polymorphonuclear leukocytes and hematopoietic stem cells. The gene for CXCL2 is located on human chromosome 4 in a cluster of other CXC chemokines. CXCL2 mobilizes cells by interacting with a cell surface chemokine receptor called CXCR2.

GH is a member of the somatotropin/prolactin family of hormones which play an important role in growth control. The gene, along with four other related genes, is located at the growth hormone locus on chromosome 17 where they are interspersed in the same transcriptional orientation; an arrangement which is thought to have evolved by a series of gene duplications. The five genes share a remarkably high degree of sequence identity. Alternative splicing generates additional isoforms of each of the five growth hormones, leading to further diversity and potential for specialization. This particular family member is expressed in the pituitary but not in placental tissue as is the case for the other four genes in the growth hormone locus. Mutations in or deletions of the gene lead to growth hormone deficiency and short stature.

SF3B14 is a 125 amino acid nuclear protein which is a component of the splicing factor 3b complex. Splicing factor 3b is involved with s with both the U2 and U11/U12 small nuclear ribonucleoprotein complexes (U2 snRNP) of spliceosomes. SF3B14 which is required for the splicing of pre-mRNA enters the spliceosome and connect with the pre-mRNA branch site facilitating the interaction of snRNP with the branch sites of U2 and U12 of the 17S U2 and the 18S U11/U12 snRNP complex.

Pre-mRNA-splicing factor SYF2 (SYF2) may be involved in pre-mRNA splicing. The SYF2 protein interacts with cyclin D-type binding-protein 1, which is believed to be a cell cycle regulator at the G1/S transition. SYF2 is amply expressed in the heart, skeletal muscle and kidney and is expressed at lower levels in other tissues.

EIF5A2 is part of the eukaryotic initiation factor 5A subfamily, is an vital protein strongly linked to cellular polyamine homeostasis. EIF5A2 promotes the formation of the first peptide bond during the initial stage of protein synthesis. EIF5A2 is the single eukaryotic protein to have a hypusine residue, which is a post-translational modification of a lysine by the addition of a butylamino group.

RUNX3 is part of the RUNX family that mediates the expression of genes which participate in cellular differentiation and cell cycle progression. RUNX3 heterodimer and the beta subunit form a complex that binds to the core DNA sequence 5''-PYGPYGGT-3'' found in several enhancers and promoters, and can either activate or suppress transcription. RUNX3 interacts with additional transcription factors. RUNX3 is a good candidate for gastric cancer tumor suppressor diagnosis.

Follicle stimulating hormone (FSH) is a hormone synthesised and secreted by gonadotropes in the anterior pituitary gland. FSH and LH act synergistically in reproduction: In women, in the ovary FSH stimulates the growth of immature Graafian follicles to maturation. As the follicle grows it releases inhibin, which shuts off the FSH production. In men, FSH enhances the production of androgen-binding protein by the Sertoli cells of the testes and is critical for spermatogenesis. In both males and females, FSH stimulates the maturation of germ cells. In females, FSH initiates follicular growth, specifically affecting granulosa cells. With the concomitant rise in inhibin B FSH levels then decline in the late follicular phase. This seems to be critical in selecting only the most advanced follicle to proceed to ovulation. At the end of the luteal phase, there is a slight rise in FSH that seems to be of importance to start the next ovulatory cycle. Like its partner, LH, FSH release at the pituitary gland is controlled by pulses of gonadotropin-releasing hormone (GnRH). Those pulses, in turn, are subject to the estrogen feed-back from the gonads.

Eukaryotic Translation Initiation Factor 4E-Binding Protein 3 (EIF4EBP3) belongs to the EIF4EBP family whose proteins bind to eukaryotic initiation factor 4E and regulate its assembly into EIF4F, the multi-subunit translation initiation factor that identifies the mRNA cap structure.

SUMF1 is a member of the SUMF family. SUMF1 catalyzes the hydrolysis of sulfate esters by oxidizing a cysteine residue in the substrate sulfatase to an active site 3-oxoalanine residue called C-alpha-formylglycine. Alterations in this gene result in multiple sulfatase deficiency which is a lysosomal storage disorder.

Krueppel-like factor 12 (KLF12) belongs to the Kruppel-like zinc finger protein family and can repress expression of the AP-2 alpha gene by binding to a particular site in the AP-2 alpha gene promoter. AP-2 alpha (Activator protein-2 alpha) is a developmentally-regulated transcription factor and vital regulator of gene expression during vertebrate development and carcinogenesis. KLF12 gene repression entails binding with a corepressor, CtBP1.

ASF1A is part of the H3/H4 family of histone chaperone proteins corresponding to the anti-silencing function-1 gene in yeast. ASF1A is an important element of the histone donor complex that functions in nucleosome assembly. ASF1A interacts with histones H3 and H4, and functions together with a chromatin assembly factor during DNA replication and repair. Deletion of ASF1A in yeast and Drosophila confers sensitivity to various DNA damaging agents and inhibitors of DNA replication, increases genomic instability and sister chromatid exchange, and activates the DNA damage checkpoint.

The bone morphogenetic proteins (BMPs) are a family of secreted signaling molecules that can induce ectopic bone growth. Many BMPs are part of the transforming growth factor-beta (TGFB) superfamily. BMPs were originally identified by an ability of demineralized bone extract to induce endochondral osteogenesis in vivo in an extraskeletal site. Based on its expression early in embryogenesis, the BMP encoded by this gene has a proposed role in early development. In addition, the fact that this BMP is closely related to BMP5 and BMP7 has lead to speculation of possible bone inductive activity.

Osteopontin is a glycoprotein that was first identified in osteoblasts and is involved in bone remodeling, immune functions in fibroblasts, macrophages, and lymphocytes during inflammation and wound healing. SPP1 binds tightly to hydroxyapatite. SPP1 forms an integral part of the mineralized matrix. SPP1 is vital to cell-matrix interaction.
Secreted Phosphoprotein-1 protects against cardiac ischemia-reperfusion injury via late preconditioning. Expression of both Ostepontin and CD44 in hepatocellular carcinoma is linked with advanced tumor stage and contributes to prognosis information. SPP1 is the most over-expressed gene in intrahepatic cholangiocarcinoma. Secreted Phosphoprotein-1 overexpression is related with interstitial lung diseases.

The cytokine Macrophage migration inhibitory factor (MIF) has been identified to be secreted by the pituitary gland and the monocyte/macrophage and to play an important role in endotoxic shock. MIF has the unique property of being released from macrophages and T cells in response to physiological concentrations of glucocorticoids. The secretion of MIF is tightly regulated and decreases at high, anti-inflammatory steroid concentration.

TAF10 is a small subunit of TFIID which is related to a subdivision of TFIID complexes. Studies with human and mammalian cells verified that this subunit is mandatory for transcriptional activation by the estrogen receptor, for progression through the cell cycle, and is essential for several cellular differentiation programs.