Parathyroid hormone suppresses insulin signaling in adipocytes.
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.
Chang
Eugene
E
Interdepartmental Nutrition Program, Purdue University, West Lafayette, IN 47907, USA.
Donkin
Shawn S
SS
Teegarden
Dorothy
D
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
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