| First Author | Zhu S | Year | 2016 |
| Journal | Diabetes | Volume | 65 |
| Issue | 3 | Pages | 699-709 |
| PubMed ID | 26647386 | Mgi Jnum | J:252954 |
| Mgi Id | MGI:5924692 | Doi | 10.2337/db15-1264 |
| Citation | Zhu S, et al. (2016) Monitoring C-Peptide Storage and Secretion in Islet beta-Cells In Vitro and In Vivo. Diabetes 65(3):699-709 |
| abstractText | Human proinsulin with C-peptide-bearing Superfolder Green Fluorescent Protein (CpepSfGFP) has been expressed in transgenic mice, driven by the Ins1 promoter. The protein, expressed exclusively in beta-cells, is processed and stored as CpepSfGFP and human insulin comprising only approximately 0.04% of total islet proinsulin plus insulin, exerting no metabolic impact. The kinetics of the release of insulin and CpepSfGFP from isolated islets appear identical. Upon a single acute stimulatory challenge in vitro, fractional release of insulin does not detectably deplete islet fluorescence. In vivo, fluorescence imaging of the pancreatic surface allows, for the first time, visual assessment of pancreatic islet insulin content, and we demonstrate that CpepSfGFP visibly declines upon diabetes progression in live lepR(db/db) mice. In anesthetized mice, after intragastric or intravenous saline delivery, pancreatic CpepSfGFP (insulin) content remains undiminished. Remarkably, however, within 20 min after acute intragastric or intravenous glucose delivery (with blood glucose concentrations reaching >15 mmol/L), a small subset of islets shows rapid dispossession of a major fraction of their stored CpepSfGFP (insulin) content, whereas most islets exhibit no demonstrable loss of CpepSfGFP (insulin). These studies strongly suggest that there are "first responder" islets to an in vivo glycemic challenge, which cannot be replicated by islets in vitro. |
