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Osteoblast-Derived Cells Express Functional Glucose-Dependent Insulinotropic Peptide Receptors¹

Institute of Molecular Medicine and Genetics, Department of Medicine, Medical College of Georgia (R.J.B., Q.Z., P.P., L.M., L.Z., R.C., H.R., F.Q., K.H.D.), and the Augusta Veterans Administration Medical Center (A.L.M., C.M.I.), Augusta, Georgia 30912

Address all correspondence and requests for reprints to: Carlos M. Isales, M.D., Medical College of Georgia, Institute of Molecular Medicine and Genetics, 1120 15th Street, Augusta, Georgia 30912. E-mail: cisales{at}mail.mcg.edu

Glucose-dependent insulinotropic peptide (GIP) is a 42-amino acid peptide synthesized and secreted from endocrine cells in the small intestine. The role of GIP in coupling nutrient intake and insulin secretion, the incretin effect, is well known. We report that GIP receptor messenger RNA and protein are present in normal bone and osteoblast-like cell lines, and that high affinity receptors for GIP can be demonstrated by [¹²⁵I]GIP binding studies. When applied to osteoblast-like cells (SaOS2), GIP stimulated increases in cellular cAMP content and intracellular calcium, with both responses being dose dependent. Moreover, administration of GIP results in elevated expression of collagen type I messenger RNA as well as an increase in alkaline phosphatase activity. Both of these effects reflect anabolic actions of presumptive osteoblasts. These results provide the first evidence that GIP receptors are present in bone and osteoblast-like cells and that GIP modulates the function of these cells.

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