Related Experiment Video
Updated: Apr 27, 2026
Modeling and Evaluation of Murine Diabetic Cardiomyopathy Model
Published on: November 29, 2024
Mig6 haploinsufficiency protects mice against streptozotocin-induced diabetes
Yi-Chun Chen1, E Scott Colvin, Katherine E Griffin
1Department of Cellular & Integrative Physiology, Indiana University School of Medicine, Indianapolis, IN, 46202, USA.
Aims/Hypothesis:
EGF and gastrin co-administration reverses type 1 diabetes in rodent models. However, the failure of this to translate into a clinical treatment suggests that EGF-mediated tissue repair is a complicated process and warrants further investigation. Thus, we aimed to determine whether EGF receptor (EGFR) feedback inhibition by mitogen-inducible gene 6 protein (MIG6) limits the effectiveness of EGF therapy and promotes type 1 diabetes development.
Methods:
We treated Mig6 (also known as Errfi1) haploinsufficient mice (Mig6 (+/-)) and their wild-type littermates (Mig6 (+/+)) with multiple low doses of streptozotocin (STZ), and monitored diabetes development via glucose homeostasis tests and histological analyses. We also investigated MIG6-mediated cytokine-induced desensitisation of EGFR signalling and the DNA damage repair response in 832/13 INS-1 beta cells.
Results:
Whereas STZ-treated Mig6 (+/+) mice became diabetic, STZ-treated Mig6 (+/-) mice remained glucose tolerant. In addition, STZ-treated Mig6 (+/-) mice exhibited preserved circulating insulin levels following a glucose challenge. As insulin sensitivity was similar between Mig6 (+/-) and Mig6 (+/+) mice, the preserved glucose tolerance in STZ-treated Mig6 (+/-) mice probably results from preserved beta cell function. This is supported by elevated Pdx1 and Irs2 mRNA levels in islets isolated from STZ-treated Mig6 (+/-) mice. Conversely, MIG6 overexpression in isolated islets compromises glucose-stimulated insulin secretion. Studies in 832/13 cells suggested that cytokine-induced MIG6 hinders EGFR activation and inhibits DNA damage repair. STZ-treated Mig6 (+/-) mice also have increased beta cell mass recovery.
Conclusions/Interpretation:
Reducing Mig6 expression promotes beta cell repair and abates the development of experimental diabetes, suggesting that MIG6 may be a novel therapeutic target for preserving beta cells.
Insights
Reducing MIG6 protein levels protected mice from developing type 1 diabetes by promoting beta cell repair and function. This suggests MIG6 is a potential therapeutic target for diabetes treatment.
Area of Science:
- Endocrinology
- Immunology
- Molecular Biology
Background:
- Epidermal Growth Factor (EGF) and gastrin co-administration showed promise in reversing type 1 diabetes in rodent models.
- The clinical translation of EGF therapy has been limited, indicating a complex tissue repair process.
- The role of Epidermal Growth Factor Receptor (EGFR) feedback inhibition by mitogen-inducible gene 6 protein (MIG6) in limiting EGF therapy effectiveness and promoting type 1 diabetes warrants investigation.
Purpose of the Study:
- To determine if EGFR feedback inhibition by MIG6 limits EGF therapy effectiveness.
- To investigate if MIG6 promotes type 1 diabetes development.
Main Methods:
- Mice with reduced Mig6 expression (haploinsufficient) and wild-type littermates were treated with streptozotocin (STZ) to induce diabetes.
- Diabetes development was monitored using glucose homeostasis tests and histological analyses.
- MIG6-mediated cytokine-induced desensitization of EGFR signaling and DNA damage repair were studied in 832/13 INS-1 beta cells.
Main Results:
- STZ-treated Mig6 haploinsufficient mice remained glucose tolerant and preserved insulin levels, unlike diabetic wild-type mice.
- Preserved beta cell function in Mig6 haploinsufficient mice was evidenced by elevated Pdx1 and Irs2 mRNA levels.
- MIG6 overexpression compromised glucose-stimulated insulin secretion, and cytokine-induced MIG6 hindered EGFR activation and DNA repair in beta cells.
Conclusions:
- Reducing Mig6 expression enhances beta cell repair and mitigates experimental diabetes development.
- MIG6 acts as a negative regulator of beta cell function and repair.
- MIG6 inhibition presents a potential therapeutic strategy for preserving beta cells in diabetes.
