Insulin Signaling in Human Visceral and Subcutaneous Adipose Tissue In Vivo
- Luigi Laviola1,
- Sebastio Perrini1,
- Angelo Cignarelli1,
- Annalisa Natalicchio1,
- Anna Leonardini1,
- Francesca De Stefano1,
- Marilena Cuscito1,
- Michele De Fazio2,
- Vincenzo Memeo2,
- Vincenzo Neri3,
- Mauro Cignarelli4,
- Riccardo Giorgino1 and
- Francesco Giorgino1
- 1Department of Emergency and Organ Transplantation, Section of Internal Medicine, Endocrinology and Metabolic Diseases, University of Bari, Bari, Italy
- 2Department of Emergency and Organ Transplantation, Section of General Surgery, University of Bari, Bari, Italy
- 3Division of General Surgery, University of Foggia, Foggia, Italy
- 4Division of Endocrinology, University of Foggia, Foggia, Italy
- Address correspondence and reprint requests to Francesco Giorgino, MD, PhD, Department of Emergency and Organ Transplantation, Section of Internal Medicine, Endocrinology and Metabolic Diseases, University of Bari, Piazza Giulio Cesare, 11, I-70124 Bari, Italy. E-mail: f.giorgino{at}endo.uniba.it
Abstract
In this study, we evaluated the activation of various insulin signaling molecules in human fat in vivo and compared signaling reactions in visceral and subcutaneous fat depots. Paired abdominal omental and subcutaneous fat biopsies were obtained from nonobese subjects with normal insulin sensitivity under basal conditions and 6 and 30 min following administration of intravenous insulin. Insulin receptor phosphorylation was more intense and rapid and insulin receptor protein content was greater in omental than in subcutaneous adipose tissue (P < 0.05). Insulin-induced phosphorylation of Akt also occurred to a greater extent and earlier in omental than in subcutaneous fat (P < 0.05) in the absence of significant changes in Akt protein content. Accordingly, phosphorylation of the Akt substrate glycogen synthase kinase-3 was more responsive to insulin stimulation in omental fat. Protein content of extracellular signal–regulated kinase (ERK)-1/2 was threefold higher in omental than in subcutaneous fat (P < 0.05), and ERK phosphorylation showed an early 6-min peak in omental fat, in contrast with a more gradual increase observed in subcutaneous fat. In conclusion, the adipocyte insulin signaling system of omental fat shows greater and earlier responses to insulin than that of subcutaneous fat. These findings may contribute to explain the biological diversity of the two fat depots.
- ERK, extracellular signal–regulated kinase
- GAPDH, glyceraldehyde-3-phosphate dehydrogenase
- GSK, glycogen synthase kinase
- IRS, insulin receptor substrate
- ITT, insulin tolerance test
- MAP, mitogen-activated protein
- PAI-1, plasminogen activator inhibitor 1
- PI, phosphatidylinositol
- PPAR, peroxisome proliferator–activated receptor
Footnotes
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The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
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- Accepted January 18, 2006.
- Received October 29, 2005.
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