Insulin-induced lipoatrophy in type I diabetes. A possible tumor necrosis factor-alpha-mediated dedifferentiation of adipocytes.
OBJECTIVE
To test the hypothesis that tumor necrosis factor (TNF)-alpha may mediate the loss and the dedifferentiation of subcutaneous fat tissue in the insulin-induced lipoatrophies of a diabetic patient who presented extensive lesions.


METHODS
An in vitro exploration of cytokine production by peripheral blood mononuclear cells (PBMC) from the reported case was performed and compared with the same explorations of PBMC from three nondiabetic subjects and three diabetic patients without lipoatrophic lesions. A proliferation test and an evaluation of TNF-alpha and interleukin (IL)-6 production from PBMC in presence of insulin were studied.


RESULTS
The production of TNF-alpha and IL-6 by the macrophages of the patient in presence of insulin were dramatically increased in comparison with control subjects. This process needed cooperation with other lymphoid cells and was abrogated by dexamethasone.


CONCLUSIONS
In our reported case, a local hyperproduction of TNF-alpha from macrophages that was induced by the injected insulin could explain the dedifferentiation of the adipocytes of the subcutaneous tissue and the reversion that was induced by the local injection of dexamethasone.
Service de Nutrition, Maladies Metaboliques et Endocrinologie, Hôpital Sainte Marguerite, University of Marseille, France.
C
C
Atlan-Gepner
P
P
Bongrand
C
C
Farnarier
L
L
Xerri
R
R
Choux
J F
JF
Gauthier
T
T
Brue
P
P
Vague
J J
JJ
Grob
B
B
Vialettes
D017667:Adipocytes / Q000187:drug effects / Q000473:pathology* / Q000502:physiology; D000273:Adipose Tissue / Q000187:drug effects / Q000473:pathology* / Q000503:physiopathology; D000328:Adult; D001284:Atrophy; D002454:Cell Differentiation; D016207:Cytokines / Q000096:biosynthesis; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy*; D005260:Female; D006801:Humans; D007328:Insulin / Q000009:adverse effects*; D015850:Interleukin-6 / Q000096:biosynthesis; D008213:Lymphocyte Activation; D008214:Lymphocytes / Q000276:immunology; D012016:Reference Values; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000502:physiology*
D016207:Cytokines; D007328:Insulin; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha