| First Author | Lu G | Year | 2016 |
| Journal | Gene Ther | Volume | 23 |
| Issue | 4 | Pages | 323-9 |
| PubMed ID | 26752353 | Mgi Jnum | J:325920 |
| Mgi Id | MGI:6878082 | Doi | 10.1038/gt.2016.1 |
| Citation | Lu G, et al. (2016) Overexpression of a glucokinase point mutant in the treatment of diabetes mellitus. Gene Ther 23(4):323-9 |
| abstractText | Glucokinase (GCK) is an important enzyme critical for glucose metabolism, and has been targeted as such in the pursuit of a cure for diabetes mellitus. We show that streptozotocin (STZ)-induced diabetic murine model exhibits low GCK expression with high blood glucose levels; moreover, aggravated glomerulonephritis is observed in the model when there is IL10 deficiency. Although T cells infiltrate into the liver and pancreas in STZ-induced diabetes mice, T helper 1 (Th1) and T helper 17 (Th17) cells decrease significantly with STZ addition in in vitro polarization. Using a mutant GCK gene (GCK 262) with a knocked out cytosine at position 2643 results in lower protein expression and more ubiquitination-led protein degradation compared with wild-type GCK (GCK 261). We further observed that hsa-mir-1302 can bind to 3'-untranslated region of mutant GCK, which can decrease GCK mRNA translation. Finally, delivery of mutant GCK by subcutaneous injection is more effective at decreasing blood glucose in the STZ-treated (STZ) murine diabetes model than insulin treatment alone. Similarly, mutant GCK consistently and moderately decreases blood glucose levels in GK rats over a period of 12 and 70 days without inducing hypoglycemia, whereas insulin is only effective over 12 h. These results suggest that mutant GCK may be a future cure for diabetes. |
