Insulin-induced Lipohypertrophy: Report of a Case with Histopathology

Fujikura, Junji; Fujimoto, Masazumi; Yasue, Shintaro; Noguchi, Michio; Masuzaki, Hiroaki; Hosoda, Kiminori; Tachibana, Takao; Sugihara, Hajime; Nakao, Kazuwa

doi:10.1507/endocrj.52.623

Cited by 56 publications

(42 citation statements)

References 16 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In contrast to our case, insulin-induced lipohypertrophy with detailed histological examinations was reported by Fujikura et al [13]. An 82-year-old woman with type 2 diabetes was treated with recombinant human insulin for 16 years.…”

Section: Discussioncontrasting

confidence: 92%

A Case of Insulin-induced Localized Lobular Panniculitis with Evidence for the Phagocytosis of Insulin by Histiocytes

et al. 2007

View full text Add to dashboard Cite

Abstract. Insulin-induced localized lipoatrophy is a well-known localized side effect. Although an immune process has been suggested as its etiology, no definitive evidence has been reported to show that insulin is involved. Here, we report the first evidence for the phagocytosis of insulin by histiocytes as a very early stage of lipoatrophy, which was reproducible in two different lobular panniculitis tissues from a 71 year-old male patient. He had taken a subcutaneous insulin injection in his arms because of a sight disturbance. Since these subcutaneous tumors were likely due to inflammation by insulin, a biopsy sample was taken from the subcutaneous tumor of his right arm with his consent. The primary antibodies for insulin (1 : 200) and CD68 (1 : 50) were obtained from DAKO (guinea pig anti-insulin and mouse anti-human CD68). HE staining revealed the infiltration of mononuclear cells and histiocytes into the subcutaneous fat tissue, and some parts of this tissue had fibrosis with rich collagen fibers. These findings are consistent with a lobular panniculitis. Some histiocytes contained intracellular substances with a positive immunoreactivity to insulin. This activity was reduced when the anti-insulin antibody was preincubated with an excess amount of insulin antigen. The same substances were also positive to CD68. Thus, the phagocytosis of insulin by histiocytes appears to occur in this region. Therefore, the activation of subcutaneous macrophages by the complex of insulin and insulin antibodies may account for the initial autoimmune process.

show abstract

Section: Discussioncontrasting

confidence: 92%

A Case of Insulin-induced Localized Lobular Panniculitis with Evidence for the Phagocytosis of Insulin by Histiocytes

et al. 2007

View full text Add to dashboard Cite

show abstract

“…Indeed, further supporting inhibition of AR transcriptional activity during fat maturation, each MIX component has been shown to induce adipogenesis in vivo (De Vos et al, 1996; Fujikura et al, 2005; Madsen et al, 2008; Masuzaki et al, 2001; Masuzaki et al, 2003). Further, testosterone production is suppressed by visceral obesity (Stanworth and Jones, 2009) and patients with visceral obesity and the metabolic syndrome have higher incidence of hypogonadism (Gould et al, 2007).…”

Section: Discussionmentioning

confidence: 76%

Feed-Forward Inhibition of Androgen Receptor Activity by Glucocorticoid Action in Human Adipocytes

Hartig

Newberg

et al. 2012

Chemistry & Biology

View full text Add to dashboard Cite

We compared transcriptomes of terminally differentiated mouse 3T3-L1 and human adipocytes to identify cell-specific differences. Gene expression and high content analysis (HCA) data identified the androgen receptor (AR) as both expressed and functional, exclusively during early human adipocyte differentiation. The AR agonist dihydrotestosterone (DHT) inhibited human adipocyte maturation by downregulation of adipocyte marker genes, but not in 3T3-L1. Interestingly, AR induction corresponded with dexamethasone activation of the glucocorticoid receptor (GR); however, when exposed to the differentiation cocktail required for adipocyte maturation, AR adopted an antagonist conformation and was transcriptionally repressed. To further explore effectors within the cocktail, we applied a novel, image-based support vector machine (SVM) classification scheme to show adipocyte differentiation components inhibit AR action. The results demonstrate human adipocyte differentiation, via GR activation, upregulates AR but also inhibits AR transcriptional activity.

show abstract

“…Repeated injection of insulin for diabetes control, for example, has been shown to induce local adipogenesis at the sites of injection (Fujikura et al, 2005). In addition, excess glucocorticoids are responsible for the excess visceral adipose tissue observed in patients with Cushing's syndrome (Rockall et al, 2003).…”

Section: Introductionmentioning

confidence: 99%

Glucocorticoid Signaling Defines a Novel Commitment State during AdipogenesisIn Vitro

Pantoja

Huff

Yamamoto

2008

MBoC

128

View full text Add to dashboard Cite

Differentiation of 3T3-L1 preadipocytes can be induced by a 2-d treatment with a factor "cocktail" (DIM) containing the synthetic glucocorticoid dexamethasone (dex), insulin, the phosphodiesterase inhibitor methylisobutylxanthine (IBMX) and fetal bovine serum (FBS). We temporally uncoupled the activities of the four DIM components and found that treatment with dex for 48 h followed by IBMX treatment for 48 h was sufficient for adipogenesis, whereas treatment with IBMX followed by dex failed to induce significant differentiation. Similar results were obtained with C3H10T1/2 and primary mesenchymal stem cells. The 3T3-L1 adipocytes differentiated by sequential treatment with dex and IBMX displayed insulin sensitivity equivalent to DIM adipocytes, but had lower sensitivity to ISO-stimulated lipolysis and reduced triglyceride content. The nondifferentiating IBMX-then-dex treatment produced transient expression of adipogenic transcriptional regulatory factors C/EBP␤ and C/EBP␦, and little induction of terminal differentiation factors C/EBP␣ and PPAR␥. Moreover, the adipogenesis inhibitor preadipocyte factor-1 (Pref-1) was repressed by DIM or by dex-then-IBMX, but not by IBMX-then-dex treatment. We conclude that glucocorticoids drive preadipocytes to a novel intermediate cellular state, the dex-primed preadipocyte, during adipogenesis in cell culture, and that Pref-1 repression may be a cell fate determinant in preadipocytes.

show abstract

Insulin-induced Lipohypertrophy: Report of a Case with Histopathology

Cited by 56 publications

References 16 publications

A Case of Insulin-induced Localized Lobular Panniculitis with Evidence for the Phagocytosis of Insulin by Histiocytes

A Case of Insulin-induced Localized Lobular Panniculitis with Evidence for the Phagocytosis of Insulin by Histiocytes

Feed-Forward Inhibition of Androgen Receptor Activity by Glucocorticoid Action in Human Adipocytes

Glucocorticoid Signaling Defines a Novel Commitment State during AdipogenesisIn Vitro

Contact Info

Product

Resources

About