| First Author | Kuo T | Year | 2016 |
| Journal | J Biol Chem | Volume | 291 |
| Issue | 18 | Pages | 9648-56 |
| PubMed ID | 26917725 | Mgi Jnum | J:233713 |
| Mgi Id | MGI:5787885 | Doi | 10.1074/jbc.M115.702183 |
| Citation | Kuo T, et al. (2016) Altered Plasma Profile of Antioxidant Proteins as an Early Correlate of Pancreatic beta Cell Dysfunction. J Biol Chem 291(18):9648-56 |
| abstractText | Insulin resistance and beta cell dysfunction contribute to the pathogenesis of type 2 diabetes. Unlike insulin resistance, beta cell dysfunction remains difficult to predict and monitor, because of the inaccessibility of the endocrine pancreas, the integrated relationship with insulin sensitivity, and the paracrine effects of incretins. The goal of our study was to survey the plasma response to a metabolic challenge in order to identify factors predictive of beta cell dysfunction. To this end, we combined (i) the power of unbiased iTRAQ (isobaric tag for relative and absolute quantification) mass spectrometry with (ii) direct sampling of the portal vein following an intravenous glucose/arginine challenge (IVGATT) in (iii) mice with a genetic beta cell defect. By so doing, we excluded the effects of peripheral insulin sensitivity as well as those of incretins on beta cells, and focused on the first phase of insulin secretion to capture the early pathophysiology of beta cell dysfunction. We compared plasma protein profiles with ex vivo islet secretome and transcriptome analyses. We detected changes to 418 plasma proteins in vivo, and detected changes to 262 proteins ex vivo The impairment of insulin secretion was associated with greater overall changes in the plasma response to IVGATT, possibly reflecting metabolic instability. Reduced levels of proteins regulating redox state and neuronal stress markers, as well as increased levels of coagulation factors, antedated the loss of insulin secretion in diabetic mice. These results suggest that a reduced complement of antioxidants in response to a mixed secretagogue challenge is an early correlate of future beta cell failure. |
