title: Parathyroid Hormone-Related Peptide (1-36) Enhances Beta Cell Regeneration and Increases Beta Cell Mass in a Mouse Model of Partial Pancreatectomy.
abstract: OBJECTIVE
  Finding ways to stimulate the regeneration of endogenous pancreatic beta cells is an important goal in the treatment of diabetes. Parathyroid hormone-related protein (PTHrP), the full-length (1-139) and amino-terminal (1-36) peptides, enhance beta cell function, proliferation, and survival. Therefore, we hypothesize that PTHrP(1-36) has the potential to regenerate endogenous beta cells.
  
  
  METHODS
  The partial pancreatectomy (PPx) mouse model of beta cell injury was used to test this hypothesis. Male Balb/c mice underwent either sham-operation or PPx, and were subsequently injected with PTHrP(1-36) (160μg/kg) or vehicle (veh), for 7, 30, or 90 days. The four groups of mice, sham-veh, sham-PTHrP, PPx-veh, and PPx-PTHrP were assessed for PTHrP and receptor expression, and glucose and beta cell homeostasis.
  
  
  RESULTS
  PTHrP-receptor, but not the ligand, was significantly up-regulated in islets from mice that underwent PPx compared to sham-operated mice. This suggests that exogenous PTHrP could further enhance beta cell regeneration after PPx. PTHrP did not significantly affect body weight, blood glucose, plasma insulin, or insulin sensitivity, in either sham or PPx mice. Glucose tolerance improved in the PPx-PTHrP versus PPx-veh mice only in the early stages of treatment. As hypothesized, there was a significant increase in beta cell proliferation in PPx-PTHrP mice at days 7 and 30; however, this was normalized by day 90, compared to PPx-veh mice. Enhanced beta cell proliferation translated to a marked increase in beta cell mass at day 90, in PPx-PTHrP versus PPx-veh mice.
  
  
  CONCLUSIONS
  PTHrP(1-36) significantly enhances beta cell regeneration through increased beta cell proliferation and beta cell mass after PPx. Future studies will determine the potential of PTHrP to enhance functional beta cell mass in the setting of diabetes.
authors.affiliation: Diabetes, Obesity and Metabolism Institute, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America.
authors.forename: Anaïs
authors.initials: A
authors.lastname: Mozar
authors.affiliation: Division of Endocrinology, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.
authors.forename: Hugo
authors.initials: H
authors.lastname: Lin
authors.affiliation: Division of Endocrinology, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.
authors.forename: Katoura
authors.initials: K
authors.lastname: Williams
authors.affiliation: Division of Endocrinology, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.
authors.forename: Connie
authors.initials: C
authors.lastname: Chin
authors.affiliation: Diabetes, Obesity and Metabolism Institute, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America.
authors.forename: Rosemary
authors.initials: R
authors.lastname: Li
authors.affiliation: Diabetes, Obesity and Metabolism Institute, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America.
authors.forename: Nagesha Guthalu
authors.initials: NG
authors.lastname: Kondegowda
authors.affiliation: Diabetes, Obesity and Metabolism Institute, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America.
authors.forename: Andrew F
authors.initials: AF
authors.lastname: Stewart
authors.affiliation: Diabetes, Obesity and Metabolism Institute, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America.
authors.forename: Adolfo
authors.initials: A
authors.lastname: Garcia-Ocaña
authors.affiliation: Diabetes, Obesity and Metabolism Institute, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America.
authors.forename: Rupangi Chhaya
authors.initials: RC
authors.lastname: Vasavada
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects*; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance; D050417:Insulin-Secreting Cells / Q000378:metabolism*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010180:Pancreatectomy; D044162:Parathyroid Hormone-Related Protein / Q000494:pharmacology*; D010446:Peptide Fragments / Q000494:pharmacology*; D044168:Receptor, Parathyroid Hormone, Type 1 / Q000096:biosynthesis; D012038:Regeneration; D013997:Time Factors; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D001786:Blood Glucose; D007328:Insulin; D044162:Parathyroid Hormone-Related Protein; D010446:Peptide Fragments; D044168:Receptor, Parathyroid Hormone, Type 1; C079957:parathyroid hormone-related peptide (1-36)