Sustained expression of GLP-1 receptor differentially modulates β-cell functions in diabetic and nondiabetic mice
| Autor: | Shugo Sasaki, Hirotaka Watada, Maureen Gannon, Mitsuyoshi Takahara, Hideaki Kaneto, Taka-aki Matsuoka, Takeshi Miyatsuka, Yuichi Yamamoto, Fumiyo Kubo, Iichiro Shimomura, Naoki Shimo |
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| Rok vydání: | 2016 |
| Předmět: |
Male
0301 basic medicine Genetically modified mouse Aging medicine.medical_specialty medicine.medical_treatment Biophysics Mice Transgenic 030209 endocrinology & metabolism Biology Biochemistry Glucagon-Like Peptide-1 Receptor Article Mice 03 medical and health sciences 0302 clinical medicine Downregulation and upregulation Insulin-Secreting Cells Internal medicine Diabetes mellitus Insulin Secretion Diabetes Mellitus medicine Animals Insulin Receptor Molecular Biology Cells Cultured Glucagon-like peptide 1 receptor geography geography.geographical_feature_category Cell Biology medicine.disease Islet Mice Inbred C57BL Glucose 030104 developmental biology Endocrinology Gene Expression Regulation PDX1 |
| Zdroj: | Biochemical and Biophysical Research Communications. 471:68-74 |
| ISSN: | 0006-291X |
| DOI: | 10.1016/j.bbrc.2016.01.177 |
| Popis: | Glucagon-like peptide 1 (GLP-1) has been shown to play important roles in maintaining β-cell functions, such as insulin secretion and proliferation. While expression levels of GLP-1 receptor (Glp1r) are compromised in the islets of diabetic rodents, it remains unclear when and to what degree Glp1r mRNA levels are decreased during the progression of diabetes. In this study, we performed real-time PCR with the islets of db/db diabetic mice at different ages, and found that the expression levels of Glp1r were comparable to those of the islets of nondiabetic db/misty controls at the age of four weeks, and were significantly decreased at the age of eight and 12 weeks. To investigate whether restored expression of Glp1r affects the diabetic phenotypes, we generated the transgenic mouse model Pdx1(PB)-CreER(TM); CAG-CAT-Glp1r (βGlp1r) that allows for induction of Glp1r expression specifically in β cells. Whereas the expression of exogenous Glp1r had no measurable effect on glucose tolerance in nondiabetic βGlp1r;db/misty mice, βGlp1r;db/db mice exhibited higher glucose and lower insulin levels in blood on glucose challenge test than control db/db littermates. In contrast, four weeks of treatment with exendin-4 improved the glucose profiles and increased serum insulin levels in βGlp1r;db/db mice, to significantly higher levels than those in control db/db mice. These differential effects of exogenous Glp1r in nondiabetic and diabetic mice suggest that downregulation of Glp1r might be required to slow the progression of β-cell failure under diabetic conditions. |
| Databáze: | OpenAIRE |
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