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

Abstract

Insulin resistance (IR) is associated with several metabolic disorders, including type 2 diabetes (T2D). The development of IR in insulin target tissues involves genetic and acquired factors. Persons at genetic risk for T2D tend to develop IR several years before glucose intolerance. Several rodent models for both IR and T2D are being used to study the disease pathogenesis; however, these models cannot recapitulate all the aspects of this complex disorder as seen in each individual. Human pluripotent stem cells (hPSCs) can overcome the hurdles faced with the classical mouse models for studying IR. Human induced pluripotent stem cells (hiPSCs) can be generated from the somatic cells of the patients without the need to destroy a human embryo. Therefore, patient-specific hiPSCs can generate cells genetically identical to IR individuals, which can help in distinguishing between genetic and acquired defects in insulin sensitivity. Combining the technologies of genome editing and hiPSCs may provide important information about the genetic factors underlying the development of different forms of IR. Further studies are required to fill the gaps in understanding the pathogenesis of IR and diabetes. In this review, we summarize the factors involved in the development of IR in the insulin-target tissues leading to diabetes. Also, we highlight the use of hPSCs to understand the mechanisms underlying the development of IR.