Antibody Therapy Development Service for T2DM

Antibody Therapy Development Service for T2DM

Non-insulin-dependent or T2DM is a metabolic disease characterized by an elevated blood glucose concentration that results from inadequate insulin action in insulin-sensitive tissues and from abnormal insulin secretion. Increasing comprehension of the cellular and biochemical defects underlying insulin resistance and T2DM has to develop new therapeutic approaches. Ace Metabolism provides a complete set of antibody therapy development service for T2DM.

Targets for T2DM

Type 2 diabetes mellitus (T2DM), is a heterogeneous disorder characterized by multiple defects in insulin action in tissues (muscle, adipose, and liver) and defects in pancreatic insulin secretion. There are molecule targets and their main function.

Target Function
GLP-1 Enhance insulin secretion from pancreatic β-cells, promote islet proliferation and suppress glucagon release
Resistin Potential inhibitor of insulin sensitivity
PTP-1B Negative regulator of insulin signaling through dephosphorylation of IR
SHIP2 Negative regulator of insulin signaling
IKKb Negative regulator of insulin signaling
Glucagon Enhances hepatic glucose output
GCK Catalyzes the first step of glycolysis
6PF-2-K/F-2,6-P2ase Regulator of glycolytic and gluconeogenic rates through production of F-2,6-P2
G-6-Pase Catalyzes the last step of gluconeogenesis
F-1,6-P2ase Regulates gluconeogenic rates
Glycogen phosphorylase Catalyzes the conversion of glycogen to glucose-1-phosphate monomers
GSK3 Inhibits glycogen synthase
Adiponectin Enhances fatty acid oxidation and inhibits hepatic glucose output
AMPK Enhances fatty acid oxidation in liver and skeletal muscle, enhances translocation of GLUT4
Insulin expression in adipose tissue Enhances insulin action in adipose tissue
11βHSD-1 Regenerates active glucocorticoids

Receptors and Cytokines Associated with T2DM

  • Insulin Receptor
    Insulin acts by binding to the insulin receptor (INSR) on the cell surface, a process that activates cell signaling. Antibodies can activate the INSR, including both spontaneously occurring human autoantibodies and mouse monoclonal antibodies. In humans, autoantibodies to the INSR typically bind at the insulin binding site. In most cases, these antibodies block insulin binding, causing severe insulin resistance and T2DM. The allosteric antibodies, antibodies that do not bind at the ligand binding site of receptors, can activate cell signaling.
  • Leptin Receptor
    Mice homozygous for the Leprdb mutation (db/db) lack the leptin receptor and display hyperphagia, obesity and T2DM. The glucose-stimulated insulin secretion (GSIS) was increased with Calcitonin Gene-Related Peptide (CGRP) mAb antibody treatment in the db/db animals (C57BL/6J strain).
  • Adipokines
    The lipid chaperone aP2/FABP4 has been implicated in the pathology of many immunometabolic diseases, including T2DM. The aP2 is not only an intracellular protein but also an active adipokine that contributes to hyperglycemia by promoting hepatic gluconeogenesis and interfering with peripheral insulin action. The secreted form of aP2 acts as an adipokine-a peptide that is secreted by adipose tissue and acts on distant organs-and regulates HGP and systemic glucose homeostasis, and contributes to insulin resistance. Serum aP2 levels are significantly elevated in obese mice, and blocking aP2 in these mice with a polyclonal antibody attenuates T2DM.
  • Cytokines
    The link between the action of cytokines, such as IL-18, and IR has a mechanistic basis involving the activation of c-Jun N-terminal kinase 1(JNK1)/signal transducer and activator of transcription (STAT) kinase pathway and phosphorylation of the serine/threonine IRS1, which is required for efficient signaling of insulin through its cognate receptor. GSK1070806 is a humanized IgG1 antibody that binds to human IL-18 with a high affinity. It can achieve the purpose of reducing inflammatory factors and improving T2DM.

Metabolic Staging of T2DMMetabolic Staging of T2DM (Chatterjee, S.; et al. The lancet, 2017)

Our Services

With years of experience in therapy development, Ace Metabolism can provide our clients with therapy development services. Our services include but not limited to the followings.

Developing Antibodies for Targeted of Intracellular

Developing Antibodies for Targets of Interest

  • Monoclonal Antibody Development
  • Antibody Drug Conjugate (ADC) Development
  • Bispecific Antibody Development
  • Allosteric Antibody Development

Antibody Drug Evaluation Services

Antibody Drug Evaluation Services

  • Pharmacokinetics of Antibodies
  • Bioavailability of Antibodies
  • Efficacy of Antibodies
  • Application Stability and Security

Features of Our Services

Highly CustomizableHighly Customizable

One-stop ServicesOne-stop Services

High QualitysHigh Quality

Professional TeamProfessional Team

With years of translational research and therapy discovery experience, Ace Metabolism can accelerate the therapeutic development and drug discovery process about T2DM for our clients worldwide. Our assays are developed and processed with the highest standard and the results are delivered on time without compromising quality. Please feel free to contact us.

References

  1. Burak, M. F.; et al. Development of a therapeutic monoclonal antibody that targets secreted fatty acid–binding protein aP2 to treat type 2 diabetes. Science translational medicine. 2015, 7(319).
  2. Riera, C. E. Can Monoclonal Antibodies against CGRP Offer New Treatment Options for Type 2 Diabetes? Journal of diabetes and clinical research. 2020, 2(4), 114.
  3. Chatterjee, S.; et al. Type 2 diabetes. The lancet. 2017, 389(10085), 2239-2251.
All of our services and products are intended for preclinical research use only and cannot be used to diagnose, treat or manage patients.
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