Insulin resistance in diabetes: The promise of using induced pluripotent stem cell technology

Table 1 Human induced pluripotent stem cells models used to study insulin resistance

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.