1. Fig. 1. GLP-1 induces miR-132 and miR-212 expression in pancreatic β-cells in vitro and in vivo. (A) MiRNA expression profiling of GLP-1 treated INS-1 832/3 cells. MiRNA profiling was performed by real-time qRT-PCR. Data represent the average of three independent measurements with cells at different passages. The x-axis of the scatter plot represents the copy number of miRNAs per 10 pg total RNA (the approximate amount of RNA per cell), and the y-axis is the ratio of miRNA expression changes in response to 50 nM GLP-1 for 24 hours. (B,C) MiRNAs 132, 212 and 375 levels in GLP-1 treated rat (B) and mice (C) islets. Pancreatic islets were isolated from male Sprague-Dawley rats and from male C57Bl/6N mice and cultured in RPMI 1640 medium with or without 50 nM GLP-1 for 24 hrs and 48hrs respectively. Levels of the miRNAs were determined by TaqMan PCR and normalized to 4.5S RNA and U6 RNA respectively. (D) Pancreatic islets were isolated and total RNA extracted 48 hour post Exendin-4 infusion, MiRNAs 132, 212 and 375 were determined by Taqman PCR and normalized to U6 RNA. Data are mean ± SE of 5 mice per group. * p< 0.05, ** p < 0.01.

2. FIG. 2. MicroRNA-132 enhances glucose stimulated insulin secretion in INS-1 832/3 cells. INS-1 832/3 cells were transfected (by electroporation) with precursors for miR-132, miR-375, and a Pre-miR TM negative control. 48 hr post transfection insulin secretion was measured in response to 2, 8 or 16 mM glucose, or 30 mMKCl with 2 mM glucose. The y- axis is depicted as fractional insulin secretion (% of insulin content) in the experiments. Data is representative of 5 independent experiments

3. Fig. 3 CACT is the direct target of the miRNAs 132 & 212 in rat pancreatic β-cells. (A) Differential expression (DE) of mRNA resulting from miRNA-132 is plotted against DE resulting from miRNA-212, 24hr following introduction of miRNA oligonucleotides into Ins-1 β-cells (p<0.05). Larger symbols indicate greater statistical significance for DE. ~3 % of the depicted mRNA have a seed region (B) INS-1 832/3 cells were infected 24 hours after seeding with adeno-virus over expressing miRNA-132 or GFP (control), cells were harvested 48 hours post infection and 25µg protein was loaded per lane; VDAC was used as a loading control. This blot is a depiction of one of 3 western blots performed. (C) INS-1 832/3 cells were co-over-expressed by a dual luciferase construct from Promega with a CACT 3'UTR and a scrambled RNA or miRNA-132 or 375 24 hours post seeding. 48 hours after which, luminescence was measured in the cells using a dual luciferase assay kit. (n = 3) cAMP mediated knockdown of CACT

5. PC-ether enhances insulin secretion

6. Palmitoyl carnitine Palmitoyl carnitine ether analogs