Mechanism | β cell feature mimicked | Description | Reference |
Glucose-inducible response elements (GIREs) | Glucose-regulatable transcription | Motifs (CACGTG) that are bound by carbohydrate response element binding protein (ChREBP) in response to elevated glucose levels | [46] - [51] |
Glucose-responsive promoters | Glucose-regulatable transcription | Promoters with enhanced activity under conditions of elevated glucose (i.e. G6Pase, L-PK, GLUT2, S14) | [47] [48] [51] [109] - [112] |
Rapamycin-inducible transcription | Glucose-regulatable transcription | Dimerizer-inducible transcription system that is only active upon administration of rapamycin | [52] |
Insulin-responsive promoters | Insulin-regulatable transcription | Promoters with altered activity in the presence of insulin (i.e. G6Pase, IGFBP-1, L-PK, PEPCK, GLUT2, S14) | [47] [48] [51] [109] - [111] |
ER-aggregating insulin analogue | Regulated secretory pathway | Insulin analogue accumulates as aggregates in ER until exposure to small molecule that induces protein disaggregation and rapid secretion | [42] |
Furin-cleavable mutation | Proinsulin processing | Replacement of two basic pairs of amino acids with furin-cleavable site to allow processing of proinsulin in any cell type | [38] [39] |
Single-chain insulin analogue | Proinsulin processing | Replacement of C-peptide with short turn-forming heptapeptide to bypass the necessity for processing by PC1/3 and PC2 | [40] |
B10 mutation | Insulin stability/bioactivity | Naturally-occurring mutation (His B10 to Asp) on the B-chain of insulin that accumulates 10 - 100-fold more than wild-type insulin | [38] [41] |
PTB binding sites | Glucose-regulated control of insulin mRNA stability/translation | Pyrimidine-rich stretch found in the 3’ UTR of insulin mRNA | [23] [24] [53] |