Leptin and Amylin Act in an Additive Manner to Activate Overlapping Signaling Pathways in Peripheral Tissues
| Autor: | John P. Chamberland, Christos S. Mantzoros, Kalliope N. Diakopoulos, Hyun Seuk Moon, Florencia Ziemke, Christina G. Fiorenza, Benjamin E. Schneider |
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| Rok vydání: | 2010 |
| Předmět: |
Advanced and Specialized Nursing
0303 health sciences medicine.medical_specialty Leptin receptor business.industry Endocrinology Diabetes and Metabolism Leptin Adipokine Adipose tissue Amylin 030209 endocrinology & metabolism 03 medical and health sciences 0302 clinical medicine Endocrinology Internal medicine Internal Medicine medicine Phosphorylation Signal transduction business Ex vivo 030304 developmental biology |
| Zdroj: | Diabetes Care. 34:132-138 |
| ISSN: | 1935-5548 0149-5992 |
| DOI: | 10.2337/dc10-0518 |
| Popis: | OBJECTIVE Amylin interacts with leptin to alter metabolism. We evaluated, for the first time, amylin- and/or leptin-activated signaling pathways in human peripheral tissues (hPTs). RESEARCH DESIGN AND METHODS Leptin and amylin signaling studies were performed in vitro in human primary adipocytes (hPAs) and human peripheral blood mononuclear cells (hPBMCs) and ex vivo in human adipose tissue (hAT) from male versus female subjects, obese versus lean subjects, and subjects with subcutaneous versus omental adipose tissue. RESULTS The long form of leptin receptor was expressed in human tissues and cells studied in ex vivo and in vitro, respectively. Leptin and amylin alone and in combination activate signal transducer and activator of transcription 3 (STAT3), AMP-activated protein kinase, Akt, and extracellular signal-regulated kinase signaling pathways in hAT ex vivo and hPAs and hPBMCs in vitro; all phosphorylation events were saturable at leptin and amylin concentrations of ∼50 and ∼20 ng/ml, respectively. The effects of leptin and amylin on STAT3 phosphorylation in hPAs and hPBMCs in vitro were totally abolished under endoplasmic reticulum stress and/or in the presence of a STAT3 inhibitor. Results similar to those in the in vitro studies were observed in hAT studied ex vivo. CONCLUSIONS Leptin and amylin activate overlapping intracellular signaling pathways in humans and have additive, but not synergistic, effects in signaling pathways studied in hPTs in vitro and ex vivo. |
| Databáze: | OpenAIRE |
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