Postnatal knockout of beta cell insulin receptor impaired insulin secretion in male mice exposed to high-fat diet stress
| Autor: | Sydney Rivers, Christy Cheung, Jinming Li, Rennian Wang, Liangyi Zhou, Amanda Oakie |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Male medicine.medical_specialty Normal diet medicine.medical_treatment 030209 endocrinology & metabolism Diet High-Fat Biochemistry 03 medical and health sciences Mice 0302 clinical medicine Endocrinology Internal medicine Insulin-Secreting Cells Glucose Intolerance Insulin Secretion medicine Animals Autocrine signalling Receptor Promoter Regions Genetic Molecular Biology Cells Cultured Mice Knockout biology Chemistry Insulin Receptor Insulin Insulin receptor Tamoxifen 030104 developmental biology Animals Newborn Knockout mouse biology.protein GLUT2 Beta cell Signal Transduction |
| Zdroj: | Molecular and cellular endocrinology. 499 |
| ISSN: | 1872-8057 |
| Popis: | The presence of insulin receptor (IR) on insulin-secreting beta cells suggests an autocrine regulatory role for insulin in its own signalling. Congenital beta cell-specific IR knockout (βIRKO) mouse studies have demonstrated the development of age-dependent glucose intolerance. We investigated the role of beta cell IR signalling specifically during postnatal life following undisturbed prenatal pancreatic development and maturation. We utilized a tamoxifen-inducible mouse insulin 1 promoter (MIP) driven Cre recombinase IR knockout mouse model (MIP-βIRKO) to achieve partial knockout of IR in islets and determine the functional role of beta cell IR in adult mice fed a control normal diet (ND) or 60% high-fat diet (HFD). At 24 weeks of age, MIP-βIRKO ND mice maintained glucose tolerance, insulin release, and unchanged beta cell mass when compared to control ND mice. In contrast, 24-week-old MIP-βIRKO mice demonstrated significant glucose intolerance and lower insulin release after 18 weeks of HFD feeding. A reduction in beta cell soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) protein expression, phosphorylated AktS473 and P70S6K1T389, and glucose transporter 2 (GLUT2) expression were also identified in MIP-βIRKO HFD islets. Overall, the postnatal knockout of beta cell IR in HFD-fed mice resulted in decreased expression of beta cell glucose-sensing and exocytotic proteins and a reduction in intracellular signalling. These findings highlight that IR expression in the adult islet is required to maintain beta cell function under hyperglycemic stress. |
| Databáze: | OpenAIRE |
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