Table 1.
Ref.
|
Disease/ syndrome
|
iPSC models
|
Main findings
|
Iovino et al[69] | DS with severe insulin resistance | Three different INSR mutations (patient-derived iPSCs): (1) Compound heterozygous A897X, exon 14; (2) Homozygous A2G, exon 1; (3) Homozygous L233P, exon 3 | iPSCs generated from patients with severe IR showed defects in the self-renewal of the patient-derived iPSCs |
Balhara et al[67] | Patient-derived iPSCs with a compound heterozygous mutation in exon 14 of INSR (A897X) | Mesenchymal progenitor cells (MPCs) generated from patient-derived iPSCs showed defects in the insulin signaling pathway and the cellular oxidative metabolism | |
Burkart et al[68] | Four different INSR mutations (patient-derived iPSCs): (1) Compound heterozygous A897X, exon 14; (2) Homozygous (A2G), exon 1; (3) Homozygous (L233P), exon 3; (4) Homozygous (E124X), exon2 | INSR-Mut hiPSCs have an impairment in the energy homeostasis as well as dysregulation of oxidative metabolism | |
Iovino et al[66] | Skeletal myotubes derived from INSR-Mut hiPSCs exhibit defects in insulin signaling, glucose uptake, and glycogen accumulation and altered insulin signaling gene expression | ||
Mori et al[74] | Congenital generalized lipodystrophy(CGL) | Two different BSCL2 mutations (patient-derived iPSCs): (1) Homozygous (E189X), exon 5; (2) Homozygous (R275X), exon 8 | The adipose tissue derived from BSCL2-Mut hiPSCs exhibit notably a decrease in the lipid droplet formation as well as diffuse cytoplasmic distribution of ADRP |
Friesen et al[75] | Familial partial lipodystrophy type 2 (FPLD2) | Heterozygous mutation in exon 1 of LMNA gene (R28W) (patient-derived iPSCs) | FPLD2-iPSCs recapitulate insulin resistance phenotypes and have lower capability for adipogenic differentiation with functional deficiency |
Jozefczuk et al[78] | Insulin resistant patients with liver steatosis | Patient-derived iPSCs | iPSCs derived from IR patients recapitulate insulin resistance and showed a decrease in AKT/mTOR signaling pathway and perturbed various cellular networks |
Ali et al[79] | Patients with psoriasis and insulin resistance | Patient-derived iPSCs | iPSCs-derived keratinocytes showed genetic alterations in the transcripts associated with IR, including IRS2 and GDF15 and glucose transporters, GLUT10 and GLUT14 |
Carcamo-Orive et al[82] | Insulin resistant patients | Patient-derived iPSCs | iPSCs derived from IR and IS individuals uncovered several IR relevant networks and identified a set of IR related driver genes |
iPSCs: Induced pluripotent stem cells; DS: Donohue syndrome; INSR: Insulin receptor; IR: Insulin resistance; MPCs: Mesenchymal progenitor cells; CGL: Congenital generalized lipodystrophy; ADRP: Adipose differentiated related protein.