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Parathyroid Hormone Suppresses Insulin Signalling in Differentiated Adipocytes
Author(s) -
Chang Eugene,
Donkin Shawn S.,
Teegarden Dorothy
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.881.3
Subject(s) - medicine , endocrinology , parathyroid hormone , insulin , glut4 , insulin resistance , vitamin d and neurology , glut1 , chemistry , insulin receptor , glucose uptake , calcium
Higher vitamin D status is associated with reduced incidence of insulin resistance and diabetes, but the mechanism has not been clarified. Vitamin D status is inversely related to serum parathyroid hormone (PTH) levels, and therefore PTH may modulate effects of vitamin D status on insulin sensitivity. The aim of this study was to investigate the effects of PTH treatment on the insulin signalling in fully differentiated murine 3T3‐L1 adipocytes. PTH treatment (24 hours, 10 nM) decreased insulinstimulated glucose uptake by 17% (P < 0.01) compared to vehicle, assessed with [ 3 H]‐2‐deoxyglucose (100 μM) following 100 nM insulin treatment for 20 min. This inhibitory effect was dose‐dependent, with a significant reduction noted at 1 nM PTH. The mRNA expression of the insulin receptor (IR), IR substrate‐1 (IRS‐1), GLUT1, and GLUT4 were significantly decreased following 24 hr PTH treatment (10 nM, P < 0.05). There was a significant reduction in insulin‐stimulated AKT activity (12%) (phosphorylated/total expression). PTH treatment (24 hr, 10 nM) significantly reduced GLUT4 (14%), but not GLUT1 protein expression. Therefore, higher vitamin D status may lead to improved insulin sensitivity by suppressing serum PTH because PTH reduced insulin‐stimulated glucose uptake, potentially by reducing insulin signalling and decreasing the expression of GLUT4. Supported by NIH DK069965.