title: Effects of physiological variations in circulating insulin levels on bone turnover in humans.
abstract: BACKGROUND
  Recent studies in mice have demonstrated that insulin signaling in osteoblasts stimulates bone formation and reduces osteoprotegerin production; the latter results in an increase in bone resorption, which then leads to the release of undercarboxylated osteocalcin from bone. Undercarboxylated osteocalcin, in turn, enhances insulin sensitivity.
  
  
  OBJECTIVE
  The objective of the study was to test whether physiological changes in insulin levels regulate bone metabolism in humans.
  
  
  METHODS
  This investigation was an analysis of samples from a prospective study.
  
  
  METHODS
  The study was conducted at a clinical research unit.
  
  
  METHODS
  Fourteen subjects underwent a 7-h stepped insulin infusion accompanied by a glucose clamp and somatostatin infusion along with replacement infusions of GH and glucagon, thus isolating possible effects of insulin on bone. Insulin was infused at rates achieving low (∼150 pmol/liter), intermediate (∼350 pmol/liter), or high (∼700 pmol/liter) plasma insulin levels.
  
  
  METHODS
  Bone turnover markers, undercarboxylated osteocalcin, and osteoprotegerin levels at the end of the low, intermediate, and high dose insulin infusions were measured.
  
  
  RESULTS
  Values for the outcome measures at the end of the intermediate- and high-dose insulin infusions were no different from values at the end of the low-dose insulin infusion. However, measures of insulin sensitivity (glucose infusion and disappearance rates) correlated positively with C-terminal telopeptide of type I collagen levels.
  
  
  CONCLUSIONS
  Acute changes in insulin levels, as occur during meals, do not regulate bone turnover, undercarboxylated osteocalcin, or osteoprotegerin levels. However, the correlation of measures of insulin sensitivity with bone resorption suggests the need for further studies in humans on the possible regulation of bone metabolism by insulin.
authors.affiliation: Endocrine Research Unit, College of Medicine, Mayo Clinic, 200 First Street SW, Rochester, Minnesota 55905, USA.
authors.forename: Rita
authors.initials: R
authors.lastname: Basu
authors.forename: James
authors.initials: J
authors.lastname: Peterson
authors.forename: Robert
authors.initials: R
authors.lastname: Rizza
authors.forename: Sundeep
authors.initials: S
authors.lastname: Khosla
mesh_terms: D015502:Absorptiometry, Photon; D015415:Biomarkers / Q000378:metabolism; D001786:Blood Glucose / Q000378:metabolism; D001842:Bone and Bones / Q000502:physiology*; D002096:C-Peptide / Q000378:metabolism; D003920:Diabetes Mellitus / Q000378:metabolism; D023381:Endpoint Determination; D005260:Female; D005934:Glucagon / Q000097:blood / Q000494:pharmacology; D015309:Glucose Clamp Technique; D019382:Human Growth Hormone / Q000097:blood / Q000494:pharmacology; D006801:Humans; D007004:Hypoglycemic Agents; D007328:Insulin / Q000097:blood*; D008297:Male; D008875:Middle Aged; D015675:Osteocalcin / Q000378:metabolism; D053244:Osteoprotegerin / Q000097:blood; D010446:Peptide Fragments / Q000378:metabolism; D011347:Procollagen / Q000378:metabolism; D011446:Prospective Studies
chemical_list: D015415:Biomarkers; D001786:Blood Glucose; D002096:C-Peptide; D007004:Hypoglycemic Agents; D007328:Insulin; D053244:Osteoprotegerin; D010446:Peptide Fragments; D011347:Procollagen; C047202:procollagen Type I N-terminal peptide; D015675:Osteocalcin; D019382:Human Growth Hormone; D005934:Glucagon