GR-Targeted Drug Development for Diabetes
Drug development targeting the glucocorticoid receptor (GR) has brought more treatment options for diabetes. Ace Therapeutics focuses on the diabetes field and provides strong support for our clients' antidiabetic drug discovery and development through professional animal models and preclinical testing services.
Introduction of Glucocorticoid Receptors
The glucocorticoid receptor (GR) is a member of the nuclear receptor superfamily. The glucocorticoid receptor has a marked effect on the insulin action of both endogenous and exogenous synthetic glucocorticoids. The role of GR in diabetes includes:
- Regulation of blood glucose levels: GR modulates hepatic glucose production by regulating genes involved in gluconeogenesis, such as Pck1 and G6pc.
- Insulin resistance: Excessive GR activation may lead to insulin resistance, further exacerbating the development of diabetes.
- Regulation of lipid metabolism: GR is involved in fatty acid catabolism and storage, affecting insulin sensitivity.
- Inflammatory response regulation: GR attenuates pancreatic β-cell damage by inhibiting the expression of inflammatory factors.
Antidiabetic Drug Development Services Targeting the GR at Ace Therapeutics
Ace Therapeutics offers a full range of solutions from early-stage discovery to preclinical studies. With our deep experience in diabetes metabolism research, we are able to provide our clients with specialized GR-targeted drug development services, including target validation, candidate molecule screening, in vitro and ex vivo efficacy evaluation and safety studies.
GR target validation and molecular screening services
- In vitro models: GR transcriptional activity assays (reporter gene assays).
- Receptor binding assay (competitive binding assay).
- Cellular models: Characterization of glycolipid metabolism in hepatocytes (e.g., HepG2) and adipocytes (e.g., 3T3-L1).
In vivo pharmacodynamic evaluation services
We evaluated the improvement of obesity-related insulin resistance by GR antagonists in DIO-STZ rats as well as in Db/db mice. Our key evaluation metrics included:
- Glucose tolerance test-GTT
- Insulin tolerance test-ITT
- Euglycemic hyperinsulinemic clamp
- Hyperglycemic clamp
- Whole body glucose turnover
- In vivo individual tissue glucose uptake
- Lipid tolerance test
- Whole body FFA turnover
- In vivo individual tissue FFA storage rate
- In vivo lipogenesis
Preclinical safety evaluation services
- HPA axis effects: detection of plasma ACTH, corticosterone levels.
- Tissue-specific toxicity: adrenal, hepatic pathological analysis.
Advantages of Our GR-Targeted Antidiabetic Drug Development Services
- Ace Therapeutics offers customized strategies to meet the needs of clients at different stages of antidiabetic drug development targeting GR.
- We have a wealth of in vivo and in vitro diabetes models and select appropriate ones for GR-targeted antidiabetic drug development based on our clients’ program needs.
- We offer a comprehensive range of in vivo and in vitro testing services to ensure a holistic assessment of GR-targeted antidiabetic drugs.
Ace Therapeutics is committed to helping our clients overcome key scientific challenges in diabetes drug discovery and development with our advanced diabetes animal modelling platform and diverse analytical technologies. Please contact us for more details and we will be happy to assist you.
References
- Li, J. X.; et al. Fresh insights into glucocorticoid-induced diabetes mellitus and new therapeutic directions. Nature Reviews Endocrinology. 2022, 18(9): 540-557.
- Dhankhar, S.; et al. Novel targets for potential therapeutic use in Diabetes mellitus. Diabetology & Metabolic Syndrome. 2023, 15(1): 17.
- Ciato, D. & Albani, A. Molecular mechanisms of glucocorticoid resistance in corticotropinomas: new developments and drug targets. Frontiers in Endocrinology. 2020, 11: 21.
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products are intended for preclinical research use only and cannot be used to diagnose, treat or
manage patients.
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