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Disruption of Growth Factor Receptor–Binding Protein 10 in the Pancreas Enhances β-Cell Proliferation and Protects Mice From Streptozotocin-Induced β-Cell Apoptosis
- Source :
- Diabetes. 61:3189-3198
- Publication Year :
- 2012
- Publisher :
- American Diabetes Association, 2012.
-
Abstract
- Defects in insulin secretion and reduction in β-cell mass are associated with type 2 diabetes in humans, and understanding the basis for these dysfunctions may reveal strategies for diabetes therapy. In this study, we show that pancreas-specific knockout of growth factor receptor–binding protein 10 (Grb10), which is highly expressed in pancreas and islets, leads to elevated insulin/IGF-1 signaling in islets, enhanced β-cell mass and insulin content, and increased insulin secretion in mice. Pancreas-specific disruption of Grb10 expression also improved glucose tolerance in mice fed with a high-fat diet and protected mice from streptozotocin-induced β-cell apoptosis and body weight loss. Our study has identified Grb10 as an important regulator of β-cell proliferation and demonstrated that reducing the expression level of Grb10 could provide a novel means to increase β-cell mass and reduce β-cell apoptosis. This is critical for effective therapeutic treatment of both type 1 and 2 diabetes.
- Subjects :
- 0303 health sciences
medicine.medical_specialty
biology
Cell growth
Endocrinology, Diabetes and Metabolism
Growth factor
medicine.medical_treatment
GRB10
Insulin
030209 endocrinology & metabolism
Type 2 diabetes
Streptozotocin
medicine.disease
3. Good health
03 medical and health sciences
Growth factor receptor binding
0302 clinical medicine
Endocrinology
Internal medicine
Diabetes mellitus
Internal Medicine
medicine
biology.protein
030304 developmental biology
medicine.drug
Subjects
Details
- ISSN :
- 1939327X and 00121797
- Volume :
- 61
- Database :
- OpenAIRE
- Journal :
- Diabetes
- Accession number :
- edsair.doi...........f30e2a4b1c502df63325edb8990be185
- Full Text :
- https://doi.org/10.2337/db12-0249