Document Detail


Lipoatrophy induced by subcutaneous insulin infusion: ultrastructural analysis and gene expression profiling.
MedLine Citation:
PMID:  20484470     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
CONTEXT AND OBJECTIVE: Subcutaneous adipose tissue (SAT) lipoatrophy (LA) is a rare complication of insulin therapy. We aimed to analyze the ultrastructural and molecular aspects of LA lesions. SETTING AND PATIENTS: Macroscopic and microscopic morphology of SAT beneath the LA areas from patients with type 1 diabetes treated with Lispro insulin by continuous sc insulin infusion was studied using magnetic resonance imaging, immunohistochemistry, electron microscopy, and quantitative PCR for adipose tissue-specific genes. RESULTS: SAT was present in LA lesions characterized by: 1) smaller, unilocular perilipin-positive adipocytes, with lipofuscin granules; 2) some "slimmed cells" losing lipid droplets as those we observed during starvation; and 3) numerous perivascular preadipocytes. We did not identify inflammatory cells. SAT in LA areas displayed a strong leptin down-regulation and an increase of AEBP1, a preadipocyte marker. CONCLUSIONS: Our results clearly indicate that the remarkable reduction in fat cell lipid droplets and adipocyte size justifies the decrease of SAT without a reduction in adipocyte number because of necrosis or apoptosis. Thus, immune cells and any other toxic damaging fat cells were not involved in the generation of LA. We speculate that adipocytes chronically exposed to high local insulin concentrations could become severely insulin resistant, dramatically increasing lipolysis and giving rise to "slimmed cells." Clinical LA regression could be explained by the active recruitment of preadipocytes, even if they were unable to differentiate and regenerate adipose tissue unless the insulin injection was removed.
Authors:
G Milan; I Murano; S Costa; A Pianta; C Tiengo; E Zulato; C Centobene; D Bruttomesso; S Cinti; R Vettor
Publication Detail:
Type:  Case Reports; Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-05-19
Journal Detail:
Title:  The Journal of clinical endocrinology and metabolism     Volume:  95     ISSN:  1945-7197     ISO Abbreviation:  J. Clin. Endocrinol. Metab.     Publication Date:  2010 Jul 
Date Detail:
Created Date:  2010-07-08     Completed Date:  2010-07-26     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0375362     Medline TA:  J Clin Endocrinol Metab     Country:  United States    
Other Details:
Languages:  eng     Pagination:  3126-32     Citation Subset:  AIM; IM    
Affiliation:
Department of Medical and Surgical Sciences, University of Padua, Via Ospedale, 105, 35128 Padua, Italy. gabriella.milan@unipd.it
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MeSH Terms
Descriptor/Qualifier:
Adipose Tissue / drug effects*,  metabolism,  pathology,  ultrastructure*
Adult
Analysis of Variance
Atrophy
Diabetes Mellitus, Type 1 / drug therapy*
Female
Gene Expression Profiling
Humans
Immunohistochemistry
Infusions, Subcutaneous / adverse effects*
Insulin / adverse effects*
Male
Microscopy, Electron, Transmission
Reverse Transcriptase Polymerase Chain Reaction
Chemical
Reg. No./Substance:
11061-68-0/Insulin

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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