title: Parathyroid hormone suppresses insulin signaling in adipocytes.
abstract: Previous reports suggest that parathyroid hormone (PTH) is associated with insulin resistance. This research investigated the effects of PTH on insulin signaling in differentiated 3T3-L1 adipocytes. PTH (10 nM, 24 h) treatment induced a reduction in insulin-stimulated glucose uptake, AKT activity (phosphorylated AKT/total AKT protein expression) and a decrease in GLUT4 and IRS-1 protein expression compared to vehicle treated controls in differentiated adipocytes. PTH treatment also induced increased phosphorylation of IRS-1 on serine 307, which suppresses insulin signaling. In addition, treatment of cells with adenyl cyclase inhibitor SQ52236 ameliorated the effects of PTH on insulin-stimulated glucose uptake, whereas inhibition of phospholipase C alpha (U73122) did not significantly alter the effects of PTH. Thus, PTH treatment of differentiated 3T3-L1 adipocytes suppresses insulin-stimulated glucose uptake and insulin signaling via cAMP pathway, potentially through the phosphorylation of IRS-1 at serine 307.
authors.affiliation: Interdepartmental Nutrition Program, Purdue University, West Lafayette, IN 47907, USA.
authors.forename: Eugene
authors.initials: E
authors.lastname: Chang
authors.forename: Shawn S
authors.initials: SS
authors.lastname: Donkin
authors.forename: Dorothy
authors.initials: D
authors.lastname: Teegarden
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism*; D000818:Animals; D005947:Glucose / Q000378:metabolism; D051272:Glucose Transporter Type 1 / Q000235:genetics / Q000378:metabolism; D051275:Glucose Transporter Type 4 / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D055504:Insulin Receptor Substrate Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D010281:Parathyroid Hormone / Q000494:pharmacology*; D010766:Phosphorylation / Q000187:drug effects; D010768:Phosphoserine / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D011972:Receptor, Insulin / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D013997:Time Factors
chemical_list: D051272:Glucose Transporter Type 1; D051275:Glucose Transporter Type 4; D007328:Insulin; D055504:Insulin Receptor Substrate Proteins; D010281:Parathyroid Hormone; D010768:Phosphoserine; D011972:Receptor, Insulin; D051057:Proto-Oncogene Proteins c-akt; D005947:Glucose