Bidwell, JosephTersey, Sarah A.Adaway, MicheleBone, Robert N.Creecy, AmyKlunk, AngelaAtkinson, Emily G.Wek, Ronald C.Robling, Alexander G.Wallace, Joseph M.Evans-Molina, Carmella2023-10-242023-10-242022Bidwell J, Tersey SA, Adaway M, et al. Nmp4, a Regulator of Induced Osteoanabolism, Also Influences Insulin Secretion and Sensitivity. Calcif Tissue Int. 2022;110(2):244-259. doi:10.1007/s00223-021-00903-7https://hdl.handle.net/1805/36607A bidirectional and complex relationship exists between bone and glycemia. Persons with type 2 diabetes (T2D) are at risk for bone loss and fracture, however, heightened osteoanabolism may ameliorate T2D-induced deficits in glycemia as bone-forming osteoblasts contribute to energy metabolism via increased glucose uptake and cellular glycolysis. Mice globally lacking Nuclear Matrix Protein 4 (Nmp4), a transcription factor expressed in all tissues and conserved between humans and rodents, are healthy and exhibit enhanced bone formation in response to anabolic osteoporosis therapies. To test whether loss of Nmp4 similarly impacted bone deficits caused by diet induced obesity, male wild type (WT) and Nmp4−/− mice (8wks) were fed either low-fat diet (LFD) or high-fat diet (HFD) for 12wks. Endpoint parameters included bone architecture, structural and estimated tissue level mechanical properties, body weight/composition, glucose-stimulated insulin secretion, glucose tolerance, insulin tolerance and metabolic cage analysis. HFD diminished bone architecture and ultimate force and stiffness equally in both genotypes. Unexpectedly, the Nmp4−/− mice exhibited deficits in pancreatic β-cell function and were modestly glucose intolerant under normal diet conditions. Despite the β-cell deficits, the Nmp4−/− mice were less sensitive to HFD-induced weight gain, increases in % fat mass, and decreases in glucose tolerance and insulin sensitivity. We conclude that Nmp4 supports pancreatic β-cell function but suppresses peripheral glucose utilization, perhaps contributing to its suppression of induced skeletal anabolism. Selective disruption of Nmp4 in peripheral tissues may provide a strategy for improving both induced osteoanabolism and energy metabolism in comorbid patients.en-USPublisher PolicyBone mechanical propertiesInsulin secretionNmp4Pancreatic β cellsType 2 diabetesArticle