title: The effects of acute hyperinsulinemia on bone metabolism.
abstract: Insulin signaling in bone-forming osteoblasts stimulates bone formation and promotes the release of osteocalcin (OC) in mice. Only a few studies have assessed the direct effect of insulin on bone metabolism in humans. Here, we studied markers of bone metabolism in response to acute hyperinsulinemia in men and women. Thirty-three subjects from three separate cohorts (n=8, n=12 and n=13) participated in a euglycaemic hyperinsulinemic clamp study. Blood samples were collected before and at the end of infusions to determine the markers of bone formation (PINP, total OC, uncarboxylated form of OC (ucOC)) and resorption (CTX, TRAcP5b). During 4 h insulin infusion (40 mU/m(2) per min, low insulin), CTX level decreased by 11% (P<0.05). High insulin infusion rate (72 mU/m(2) per min) for 4 h resulted in more pronounced decrease (-32%, P<0.01) whereas shorter insulin exposure (40 mU/m(2) per min for 2 h) had no effect (P=0.61). Markers of osteoblast activity remained unchanged during 4 h insulin, but the ratio of uncarboxylated-to-total OC decreased in response to insulin (P<0.05 and P<0.01 for low and high insulin for 4 h respectively). During 2 h low insulin infusion, both total OC and ucOC decreased significantly (P<0.01 for both). In conclusion, insulin decreases bone resorption and circulating levels of total OC and ucOC. Insulin has direct effects on bone metabolism in humans and changes in the circulating levels of bone markers can be seen within a few hours after administration of insulin.
authors.affiliation: Department of Cell Biology and AnatomyInstitute of Biomedicine, University of Turku, FI-20520 Turku, FinlandDepartment of MedicineUniversity of Helsinki and Helsinki University Central Hospital, Helsinki, FinlandTurku PET CentreUniversity of Turku, Turku, FinlandDepartment of RadiologyUniversity of Turku, Turku, FinlandMedical Imaging Centre of Southwest FinlandTurku University Hospital, Turku, FinlandDepartment of EndocrinologyTurku University Hospital, Turku, FinlandAbdominal Center: EndocrinologyUniversity of Helsinki and Helsinki University Central Hospital, Helsinki, FinlandMinerva Foundation Institute for Medical ResearchHelsinki, Finland kaisa.ivaska@utu.fi.
authors.forename: Kaisa K
authors.initials: KK
authors.lastname: Ivaska
authors.affiliation: Department of Cell Biology and AnatomyInstitute of Biomedicine, University of Turku, FI-20520 Turku, FinlandDepartment of MedicineUniversity of Helsinki and Helsinki University Central Hospital, Helsinki, FinlandTurku PET CentreUniversity of Turku, Turku, FinlandDepartment of RadiologyUniversity of Turku, Turku, FinlandMedical Imaging Centre of Southwest FinlandTurku University Hospital, Turku, FinlandDepartment of EndocrinologyTurku University Hospital, Turku, FinlandAbdominal Center: EndocrinologyUniversity of Helsinki and Helsinki University Central Hospital, Helsinki, FinlandMinerva Foundation Institute for Medical ResearchHelsinki, Finland.
authors.forename: Maikki K
authors.initials: MK
authors.lastname: Heliövaara
authors.affiliation: Department of Cell Biology and AnatomyInstitute of Biomedicine, University of Turku, FI-20520 Turku, FinlandDepartment of MedicineUniversity of Helsinki and Helsinki University Central Hospital, Helsinki, FinlandTurku PET CentreUniversity of Turku, Turku, FinlandDepartment of RadiologyUniversity of Turku, Turku, FinlandMedical Imaging Centre of Southwest FinlandTurku University Hospital, Turku, FinlandDepartment of EndocrinologyTurku University Hospital, Turku, FinlandAbdominal Center: EndocrinologyUniversity of Helsinki and Helsinki University Central Hospital, Helsinki, FinlandMinerva Foundation Institute for Medical ResearchHelsinki, Finland.
authors.forename: Pertti
authors.initials: P
authors.lastname: Ebeling
authors.affiliation: Department of Cell Biology and AnatomyInstitute of Biomedicine, University of Turku, FI-20520 Turku, FinlandDepartment of MedicineUniversity of Helsinki and Helsinki University Central Hospital, Helsinki, FinlandTurku PET CentreUniversity of Turku, Turku, FinlandDepartment of RadiologyUniversity of Turku, Turku, FinlandMedical Imaging Centre of Southwest FinlandTurku University Hospital, Turku, FinlandDepartment of EndocrinologyTurku University Hospital, Turku, FinlandAbdominal Center: EndocrinologyUniversity of Helsinki and Helsinki University Central Hospital, Helsinki, FinlandMinerva Foundation Institute for Medical ResearchHelsinki, Finland.
authors.forename: Marco
authors.initials: M
authors.lastname: Bucci
authors.affiliation: Department of Cell Biology and AnatomyInstitute of Biomedicine, University of Turku, FI-20520 Turku, FinlandDepartment of MedicineUniversity of Helsinki and Helsinki University Central Hospital, Helsinki, FinlandTurku PET CentreUniversity of Turku, Turku, FinlandDepartment of RadiologyUniversity of Turku, Turku, FinlandMedical Imaging Centre of Southwest FinlandTurku University Hospital, Turku, FinlandDepartment of EndocrinologyTurku University Hospital, Turku, FinlandAbdominal Center: EndocrinologyUniversity of Helsinki and Helsinki University Central Hospital, Helsinki, FinlandMinerva Foundation Institute for Medical ResearchHelsinki, Finland Department of Cell Biology and AnatomyInstitute of Biomedicine, University of Turku, FI-20520 Turku, FinlandDepartment of MedicineUniversity of Helsinki and Helsinki University Central Hospital, Helsinki, FinlandTurku PET CentreUniversity of Turku, Turku, FinlandDepartment of RadiologyUniversity of Turku, Turku, FinlandMedical Imaging Centre of Southwest FinlandTurku University Hospital, Turku, FinlandDepartment of EndocrinologyTurku University Hospital, Turku, FinlandAbdominal Center: EndocrinologyUniversity of Helsinki and Helsinki University Central Hospital, Helsinki, FinlandMinerva Foundation Institute for Medical ResearchHelsinki, Finland Department of Cell Biology and AnatomyInstitute of Biomedicine, University of Turku, FI-20520 Turku, FinlandDepartment of MedicineUniversity of Helsinki and Helsinki University Central Hospital, Helsinki, FinlandTurku PET CentreUniversity of Turku, Turku, FinlandDepartment of RadiologyUniversity of Turku, Turku, FinlandMedical Imaging Centre of Southwest FinlandTurku University Hospital, Turku, FinlandDepartment of EndocrinologyTurku University Hospital, Turku, FinlandAbdominal Center: EndocrinologyUniversity of Helsinki and Helsinki University Central Hospital, Helsinki, FinlandMinerva Foundation Institute for Medical ResearchHelsinki, Finland.
authors.forename: Ville
authors.initials: V
authors.lastname: Huovinen
authors.affiliation: Department of Cell Biology and AnatomyInstitute of Biomedicine, University of Turku, FI-20520 Turku, FinlandDepartment of MedicineUniversity of Helsinki and Helsinki University Central Hospital, Helsinki, FinlandTurku PET CentreUniversity of Turku, Turku, FinlandDepartment of RadiologyUniversity of Turku, Turku, FinlandMedical Imaging Centre of Southwest FinlandTurku University Hospital, Turku, FinlandDepartment of EndocrinologyTurku University Hospital, Turku, FinlandAbdominal Center: EndocrinologyUniversity of Helsinki and Helsinki University Central Hospital, Helsinki, FinlandMinerva Foundation Institute for Medical ResearchHelsinki, Finland.
authors.forename: H Kalervo
authors.initials: HK
authors.lastname: Väänänen
authors.affiliation: Department of Cell Biology and AnatomyInstitute of Biomedicine, University of Turku, FI-20520 Turku, FinlandDepartment of MedicineUniversity of Helsinki and Helsinki University Central Hospital, Helsinki, FinlandTurku PET CentreUniversity of Turku, Turku, FinlandDepartment of RadiologyUniversity of Turku, Turku, FinlandMedical Imaging Centre of Southwest FinlandTurku University Hospital, Turku, FinlandDepartment of EndocrinologyTurku University Hospital, Turku, FinlandAbdominal Center: EndocrinologyUniversity of Helsinki and Helsinki University Central Hospital, Helsinki, FinlandMinerva Foundation Institute for Medical ResearchHelsinki, Finland Department of Cell Biology and AnatomyInstitute of Biomedicine, University of Turku, FI-20520 Turku, FinlandDepartment of MedicineUniversity of Helsinki and Helsinki University Central Hospital, Helsinki, FinlandTurku PET CentreUniversity of Turku, Turku, FinlandDepartment of RadiologyUniversity of Turku, Turku, FinlandMedical Imaging Centre of Southwest FinlandTurku University Hospital, Turku, FinlandDepartment of EndocrinologyTurku University Hospital, Turku, FinlandAbdominal Center: EndocrinologyUniversity of Helsinki and Helsinki University Central Hospital, Helsinki, FinlandMinerva Foundation Institute for Medical ResearchHelsinki, Finland.
authors.forename: Pirjo
authors.initials: P
authors.lastname: Nuutila
authors.affiliation: Department of Cell Biology and AnatomyInstitute of Biomedicine, University of Turku, FI-20520 Turku, FinlandDepartment of MedicineUniversity of Helsinki and Helsinki University Central Hospital, Helsinki, FinlandTurku PET CentreUniversity of Turku, Turku, FinlandDepartment of RadiologyUniversity of Turku, Turku, FinlandMedical Imaging Centre of Southwest FinlandTurku University Hospital, Turku, FinlandDepartment of EndocrinologyTurku University Hospital, Turku, FinlandAbdominal Center: EndocrinologyUniversity of Helsinki and Helsinki University Central Hospital, Helsinki, FinlandMinerva Foundation Institute for Medical ResearchHelsinki, Finland Department of Cell Biology and AnatomyInstitute of Biomedicine, University of Turku, FI-20520 Turku, FinlandDepartment of MedicineUniversity of Helsinki and Helsinki University Central Hospital, Helsinki, FinlandTurku PET CentreUniversity of Turku, Turku, FinlandDepartment of RadiologyUniversity of Turku, Turku, FinlandMedical Imaging Centre of Southwest FinlandTurku University Hospital, Turku, FinlandDepartment of EndocrinologyTurku University Hospital, Turku, FinlandAbdominal Center: EndocrinologyUniversity of Helsinki and Helsinki University Central Hospital, Helsinki, FinlandMinerva Foundation Institute for Medical ResearchHelsinki, Finland.
authors.forename: Heikki A
authors.initials: HA
authors.lastname: Koistinen
keywords: bone; bone turnover markers; hyperinsulinemic clamp; insulin; osteocalcin