Normal bone density obtained in the absence of insulin receptor expression in bone - PubMed (original) (raw)
Comparative Study
. 2006 Dec;147(12):5760-7.
doi: 10.1210/en.2006-0700. Epub 2006 Sep 14.
Affiliations
- PMID: 16973725
- DOI: 10.1210/en.2006-0700
Comparative Study
Normal bone density obtained in the absence of insulin receptor expression in bone
Regina Irwin et al. Endocrinology. 2006 Dec.
Abstract
Type I diabetes is characterized by little or no insulin production and hyperglycemic conditions. It is also associated with significant bone loss and increased bone marrow adiposity. To examine the role of reduced insulin signaling in type I diabetic bone loss without inducing hyperglycemia, we used genetically reconstituted insulin receptor knockout mice (IRKO-L1) that are euglycemic as a result of human insulin receptor transgene expression in the pancreas, liver, and brain. RT-PCR analyses demonstrated undetectable levels of insulin receptor expression in IRKO-L1 bone, yet IRKO-L1 bones exhibit similar (and trend toward greater) bone density compared with wild-type animals as determined by microcomputed tomography. More detailed bone analyses indicated that cortical bone area was increased in tibias of IRKO-L1 mice. Osteoblast markers (osteocalcin and runx2 mRNA levels) and resorption markers (serum pyridinoline levels) were similar in wild-type and IRKO-L1 bones. When marrow adiposity was examined, we noticed a decrease in adipocyte number and fatty-acid-binding protein 2 expression in IRKO-L1 mice compared with wild-type mice. Bone marrow stromal cell cultures obtained from wild-type and IRKO-L1 mice demonstrated similar adipogenic and osteogenic potentials, indicating that systemic factors likely contribute to differences in marrow adiposity in vivo. Interestingly, IGF-I receptor mRNA levels were elevated in IRKO-L1 bones, suggesting (in combination with hyperinsulinemic conditions) that increased IGF-I receptor signaling may represent a compensatory response and contribute to the changes in cortical bone. Taken together, these results suggest that reduced insulin receptor signaling in bone is not a major factor contributing to bone loss in type I diabetes.
Similar articles
- Caspase-2 deficiency protects mice from diabetes-induced marrow adiposity.
Coe LM, Lippner D, Perez GI, McCabe LR. Coe LM, et al. J Cell Biochem. 2011 Sep;112(9):2403-11. doi: 10.1002/jcb.23163. J Cell Biochem. 2011. PMID: 21538476 - Congenic mice with low serum IGF-I have increased body fat, reduced bone mineral density, and an altered osteoblast differentiation program.
Rosen CJ, Ackert-Bicknell CL, Adamo ML, Shultz KL, Rubin J, Donahue LR, Horton LG, Delahunty KM, Beamer WG, Sipos J, Clemmons D, Nelson T, Bouxsein ML, Horowitz M. Rosen CJ, et al. Bone. 2004 Nov;35(5):1046-58. doi: 10.1016/j.bone.2004.07.008. Bone. 2004. PMID: 15542029 - Accelerated endothelial dysfunction in mild prediabetic insulin resistance: the early role of reactive oxygen species.
Duncan ER, Walker SJ, Ezzat VA, Wheatcroft SB, Li JM, Shah AM, Kearney MT. Duncan ER, et al. Am J Physiol Endocrinol Metab. 2007 Nov;293(5):E1311-9. doi: 10.1152/ajpendo.00299.2007. Epub 2007 Aug 21. Am J Physiol Endocrinol Metab. 2007. PMID: 17711985 - Mechanisms of marrow adiposity and its implications for skeletal health.
Veldhuis-Vlug AG, Rosen CJ. Veldhuis-Vlug AG, et al. Metabolism. 2017 Feb;67:106-114. doi: 10.1016/j.metabol.2016.11.013. Epub 2016 Nov 27. Metabolism. 2017. PMID: 28081773 Free PMC article. Review. - Novel functions for insulin in bone.
Fulzele K, Clemens TL. Fulzele K, et al. Bone. 2012 Feb;50(2):452-6. doi: 10.1016/j.bone.2011.06.018. Epub 2011 Jun 24. Bone. 2012. PMID: 21723973 Review.
Cited by
- Type 2 diabetic mellitus related osteoporosis: focusing on ferroptosis.
Chen Y, Zhao W, Hu A, Lin S, Chen P, Yang B, Fan Z, Qi J, Zhang W, Gao H, Yu X, Chen H, Chen L, Wang H. Chen Y, et al. J Transl Med. 2024 Apr 30;22(1):409. doi: 10.1186/s12967-024-05191-x. J Transl Med. 2024. PMID: 38693581 Free PMC article. Review. - Genetic activation of glycolysis in osteoblasts preserves bone mass in type I diabetes.
Ji X, Seeley R, Li K, Song F, Liao X, Song C, Angelozzi M, Valeri A, Marmo T, Lee WC, Shi Y, Long F. Ji X, et al. Cell Chem Biol. 2023 Sep 21;30(9):1053-1063.e5. doi: 10.1016/j.chembiol.2023.07.003. Epub 2023 Aug 9. Cell Chem Biol. 2023. PMID: 37562406 Free PMC article. - MSI1 Stabilizes MACF1 to Inhibit Apoptosis of MC3T3-E1 Cells Induced by High Glucose and Promote Osteogenic Differentiation Through Wnt/β-Catenin Signaling Pathway.
Zou L, Xiang C, Lu M. Zou L, et al. Mol Biotechnol. 2023 Jul;65(7):1085-1095. doi: 10.1007/s12033-022-00617-7. Epub 2022 Nov 28. Mol Biotechnol. 2023. PMID: 36443618 - Roles of Gut Microbiome in Bone Homeostasis and Its Relationship with Bone-Related Diseases.
Zemanova N, Omelka R, Mondockova V, Kovacova V, Martiniakova M. Zemanova N, et al. Biology (Basel). 2022 Sep 26;11(10):1402. doi: 10.3390/biology11101402. Biology (Basel). 2022. PMID: 36290306 Free PMC article. Review. - Impaired Glucose Metabolism, Anti-Diabetes Medications, and Risk of Thyroid Cancer.
Kushchayeva Y, Kushchayev S, Jensen K, Brown RJ. Kushchayeva Y, et al. Cancers (Basel). 2022 Jan 22;14(3):555. doi: 10.3390/cancers14030555. Cancers (Basel). 2022. PMID: 35158824 Free PMC article. Review.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Medical
Molecular Biology Databases