Fig. 1: An animal model to examine the role of abundant Insr in β-cells.

a INSR protein (isoform A and B) and INSR mRNA expression across human tissues. Left 3 columns show INSR isoform A and B protein abundance expressed as normalized median intensity (NMI; www.proteomicsdb.org). Right 3 columns show total INSR mRNA expression in the same tissues (where available) extracted from three databases. Left to right, mRNA data from human proteome atlas (HPA) and genotype tissue expression project (GTEX) are shown in reads per kilobase million (RPKM). Data from the FAMTOMS database is shown as transcripts per kilobase million (TMP). High and low expression levels within a dataset are indicated by red and blue cells, respectively. b Human INSR expression in islet cell subtypes extracted from an integrated dataset of human single cell RNA seq data (see “Methods” and “Data availability” sections). Normalized expression levels are shown in UMAP space (top) and as a ridge plot on a log scale (bottom). The height of the ridge indicates the frequency of cells at a given expression level. c Breeding strategy for generating β-cell specific βInsr^KO, βInsr^HET, and littermate control Cre-only mice. d Robust Cre recombination verified by live cell imaging of the nTnG reporter allele (GFP = green; tdTomato = red) in an isolated islet from an Ins1^Cre/wt;nTnG mouse incubated with with CellMask™ Deep Red Plasma membrane stain (white). Similar recombination was observed across multiple independent experiments (n > 10). e Western blot of Insr protein in islets isolated from individual βInsr^KO (dark red), βInsr^HET (light pink), and littermate control mice (black). Similar results were observed in islets from individual mice (n = 5). f Insr mRNA expression across tissues in 16 week-old LFD-fed control (black bars), βInsr^HET(female = light pink bars, male = light blue bars) and βInsr^KO mice (female = dark red bars, male = dark blue bars) assessed by qPCR (n = tissues from 3 females, n = tissues 5–6 in males). Data were analysed by a mixed-effects model with correction for multiple comparisons using Dunnett’s method. All data are presented as mean values +/− SEM. All animals/samples were handled in a strictly blinded manner. Source data are provided as Source Data file.