Table 1.
miRNAs implicated in regulating components of glucose-stimulated insulin secretion.
GSIS Process | miRNA–mRNA Interactions 1 | Model System 2 | Ref. |
---|---|---|---|
Glucose or fuel uptake and glucose metabolism | miR-29 a/b, miR-124 --| Mct1 | MIN6 | [59] |
miR-195-5p --| Glut3 | T24 | [56] | |
miR-143/145 --| HK2 | 293T, RCC | [62,63] | |
Membrane depolarization and Ca2+ influx | miR-124a2 → Kcnj11, Abcc8 | MIN6 | [46] |
miR-145 → Cacna1c | mouse smooth muscle | [64] | |
miR-103 --| Cacna1c/2d1, Cacnb1 | COS-7, rat neurons | [65] | |
miR-328 --| Cacna1c, Cacnb1 | HEK293, atrial tissues rat, mouse, dog | [66] | |
Exocytotic process | miR-375 --| Mtpn | MIN6 | [67] |
miR-7a --| Snca, Cspa, Cplx1 | MIN6, mouse islets | [68] | |
miR-335 --| Stxbp1 | INS-1 832/13 | [35] | |
miR-9 → Slp4 | MIN6 | [69] | |
miR-29a/b/c → Slp4 | MIN6, mouse islets | [70] | |
miR-124a → Snap25, Stx1a, Rab3A | MIN6B1 | [71] | |
miR-96 → Slp4 | MIN6B1 | [71] | |
miR-124a --| Rab27A | MIN6B1 | [71] | |
miR-124a, miR-96 -?-| Noc2 | MIN6B1 | [71] | |
miR-34a --| Vamp-2 | MIN6B1 | [72] | |
miR-29a --| Stx1a | INS-1E | [73] | |
Insulin gene regulation 3 | miR-30d --| Map4k4 | MIN6 | [74] |
miR-15a --| Ucp2 | MIN6 | [75] | |
miR-375 --| PDK1 | INS-1E | [76] | |
miR-24, miR-148a --| Sox6 | mouse islets | [37] | |
miR-182 --| Bhlhe22 | mouse islets | [37] |
1 Direct negative regulatory targeting denoted by miRNA --| mRNA; indirect targeting with positive effect, miRNA → mRNA; indirect targeting with negative effect, miRNA -?-| mRNA. Interactions are experimentally validated by reporter assays, and/or modulation of miRNA levels. Gene nomenclature according to HGNC guidelines, e.g., human gene: MTPN, ortholog rodent gene: Mtpn [77]. In some studies, rodent cell lines have been used to validate miRNA targeting of human gene 3'UTR in plasmid vectors. 2 Included also are studies on non-beta cell model systems where miRNA-dependent regulation of known components of GSIS has been demonstrated. 3 Insulin gene regulation is not a process of GSIS per se but an important factor in determining the amount of insulin available for subsequent release.