Increasing β-Cell Mass Requires Additional Stimulation for Adaptation to Secretory Demand
| العنوان: | Increasing β-Cell Mass Requires Additional Stimulation for Adaptation to Secretory Demand |
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| المؤلفون: | Woo Jin Song, Yuan-Yuan Li, Prosenjit Mondal, Mehboob A. Hussain, Kil S. Yang |
| المصدر: | Molecular Endocrinology. 29:108-120 |
| بيانات النشر: | The Endocrine Society, 2015. |
| سنة النشر: | 2015 |
| مصطلحات موضوعية: | Agonist, medicine.medical_specialty, medicine.drug_class, medicine.medical_treatment, Incretin, Cell Count, Mice, Transgenic, Carbohydrate metabolism, Biology, Diet, High-Fat, Glucagon-Like Peptide-1 Receptor, Mice, Endocrinology, Insulin-Secreting Cells, Diabetes mellitus, Internal medicine, Glucose Intolerance, medicine, Animals, Insulin, Receptor, Pancreas, Molecular Biology, Cell Proliferation, Original Research, Glucose tolerance test, medicine.diagnostic_test, Type 2 Diabetes Mellitus, General Medicine, Glucose Tolerance Test, medicine.disease, Mice, Inbred C57BL, Glucose, Diabetes Mellitus, Type 2, Cyclin A2 |
| الوصف: | Type 2 diabetes mellitus (T2DM) is caused by relative insulin deficiency, subsequent to both reduced β-cell mass and insufficient insulin secretion, and both augmenting β-cell mass and β-cell function are therapeutic strategies for treating T2DM. However, the relative significance of increasing β-cell mass vs improving β-cell stimulus secretion coupling remains unclear. We have developed a mouse model that allows proliferation of β-cells in adult mice without affecting β-cell function by inducible expression of the positive cell cycle regulator cyclin A2 specifically in β-cells. In these mice, when kept on a standard diet, doubling of β-cell mass does not result in altered glucose tolerance or glucose-stimulated circulating insulin levels. Notably, a doubling of β-cell mass also does not confer improved glycemic control and ability of β-cells to respond to diabetogenic high-fat diet-induced glucose intolerance. However, in high-fat diet-exposed mice, an increase in endogenous β-cell mass confers increased potentiation of in vivo glucose-stimulated rise in circulating insulin in response to acute pharmacologic treatment with the incretin glucagon-like peptide-1 receptor agonist exendin-4. These observations indicate that increasing endogenous β-cell mass may not be sufficient to improve glycemic control in T2DM without additional strategies to increase β-cell stimulus secretion coupling. |
| تدمد: | 1944-9917 0888-8809 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::59742d7091c7ca084659f5ef8331bcecTest https://doi.org/10.1210/me.2014-1265Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....59742d7091c7ca084659f5ef8331bcec |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 19449917 08888809 |
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