Type 2 diabetes mellitus (T2DM) is one of the major health concern among the world. Several treatment options for T2DM are in clinical use, including injecting
insulin, promoting insulin secretion by
insulin secretagogues, and improving
insulin sensitivity by
insulin sensitizers. However, increasing the amount of
insulin receptor in
insulin-target tissues has not been explored. In order to test the efficacy of
insulin receptor overexpression for improving
glucose control, we established a transgenic mouse line expressing human
insulin receptor (INSR). We analyzed, growth, energy balance, and
glucose control of INSR-overexpressing db/db mice (INSR; db/db), which we produced by mating INSR transgenic mice with db/db mice, a genetic model of
obesity due to insufficient
leptin signaling. Compared to db/db mice, INSR; db/db mice were rescued from
hyperphagia and
obesity, leading to improved
blood glucose levels. Unexpectedly, however, INSR; db/db mice presented with
stunted growth, accompanied by decreased plasma levels of free IGF1 and
IGFBP-3, indicating the down-regulation of GH/IGF1 axis. These phenotypes were observed in INSR; db/db mice but not in INSR littermates. Meanwhile, bone defects observed in db/db male mice were not rescued. Moreover, improved
blood glucose was not accompanied by improved
insulin sensitivity. Therefore, overexpression of
insulin receptor improves obese and diabetic phenotypes in db/db mice, with consequences on growth.