INSULIN-INDUCED LIPOATROPHY IN TYPE-I DIABETES - A POSSIBLE TUMOR NECROSIS FACTOR-ALPHA-MEDIATED DEDIFFERENTIATION OF ADIPOCYTES

OBJECTIVE - To lest the hypothesis that tumor necrosis factor (TNF)-al pha may mediate the loss and the dedifferentiation of subcutaneous fat tissue in the insulin induced lipoatrophies of a diabetic patient who presented extensive lesions. RESEARCH DESIGN AND METHODS - An in vitr o exploration of cytokine production by peripheral blood mononuclear c ells (PBMC) from the reported case was performed and compared with the same explorations of PBMC from three nondiabetic subjects and three d iabetic patients without lipoatrophic lesions, A proliferation test an d an evaluation of TNF-alpha and interleukin (IL)-6 production from PB MC in presence of insulin were studied. RESULTS - The production of TN F-alpha and IL-6 by the macrophages of the patient in presence of insu lin were dramatically increased in comparison with control subjects, T his process needed cooperation with other lymphoid cells and was abrog ated by dexamethasone. CONCLUSIONS - In our reported case, a local hyp erproduction of TNF-alpha from macrophages that was induced by the inj ected insulin could explain the dedifferentiation of the adipocytes of the subcutaneous tissue and the reversion that was induced by the loc al injection of dexamethasone.