Open AccessContributions of the Insulin/Insulin-Like Growth Factor-1 Axis to Diabetic Osteopathy
Author(s) -
John L. Fowlkes,
Clay Bunn R,
Kathryn M. Thrailkill
Publication year - 2012
Publication title -
journal of diabetes and metabolism
Language(s) - English
Resource type - Journals
ISSN - 2155-6156
DOI - 10.4172/2155-6156.s1-003
Subject(s) - insulin receptor , insulin receptor substrate , insulin , irs1 , signal transduction , diabetes mellitus , insulin like growth factor , medicine , microbiology and biotechnology , phosphatidylinositol , receptor , phosphorylation , proto oncogene proteins c akt , endocrinology , growth factor , pi3k/akt/mtor pathway , insulin resistance , biology
Recent studies in diabetic humans and rodent models of diabetes have identified osteopathy as a serious complication of type 1 (T1D) and type 2 (T2D) diabetes. Accumulating evidence suggests that disruption of insulin and insulin-like growth factor 1 (IGF-1) homeostasis in the diabetic condition may be responsible for the observed skeletal deficits. Indeed, replacement of insulin or IGF-1 in rodent models of T1D results in significant improvement in bone healing despite ongoing moderate to severe hyperglycemia. Insulin and IGF-1 act through distinct receptors. Mice in which the receptor for insulin or IGF-1 is selectively deleted from osteoblast lineages show skeletal deficits. Despite acting through distinct receptors, insulin and IGF-1 exert their cellular activities via conserved intracellular signaling proteins. Genetic manipulation of these signaling proteins, such as insulin receptor substrate (IRS)-1 and -2, Protein Kinase B (Akt), and MAPK/ERK kinase (MEK), has uncovered a significant role for these signal transduction pathways in skeletal homeostasis. In addition to effects on skeletal physiology via canonical signaling pathways, insulin and IGF-1 may crosstalk with wingless-int. (Wnt) and bone morphogenic protein 2 (BMP-2) signaling pathways in cells of the osteoblast lineage and thereby promote skeletal development. In this review, a discussion is presented regarding the role of insulin and IGF-1 in skeletal physiology and disruptions of this axis that occur in the diabetic condition which could underlie many of the skeletal pathologies observed.