| First Author | Oakie A | Year | 2020 |
| Journal | Mol Cell Endocrinol | Volume | 499 |
| Pages | 110588 | PubMed ID | 31541682 |
| Mgi Jnum | J:282939 | Mgi Id | MGI:6384190 |
| Doi | 10.1016/j.mce.2019.110588 | Citation | Oakie A, et al. (2020) Postnatal knockout of beta cell insulin receptor impaired insulin secretion in male mice exposed to high-fat diet stress. Mol Cell Endocrinol 499:110588 |
| abstractText | 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 (betaIRKO) 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-betaIRKO) 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-betaIRKO ND mice maintained glucose tolerance, insulin release, and unchanged beta cell mass when compared to control ND mice. In contrast, 24-week-old MIP-betaIRKO 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 Akt(S473) and P70S6K1(T389), and glucose transporter 2 (GLUT2) expression were also identified in MIP-betaIRKO 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. |
