Abbreviations: BMI, body mass index; DMEM, Dulbecco's Modified Eagle Medium; HbA 1c , hemoglobin A 1c ; HOMA-IR, homeostasis model assessment-estimated insulin resistance Aims/hypothesis: Regional deposition of adipose tissue and adipocyte morphology may contribute to increased risk for insulin resistance. The aim of this study was to compare adipocyte cell size and size distribution from multiple fat depots and to determine the association with type 2 diabetes mellitus, anthropomorphic data, and subjects' metabolic profile.Methods: Clinical data and adipose tissue from subcutaneous fat, omentum, and mesentery were collected from 30 subjects with morbid obesity. Adipocytes were isolated by collagenase digestion and sized by microscopic measurement of cell diameter.Results: Overall, adipocytes from subcutaneous fat were larger than those from omentum or mesentery. For the subcutaneous and omental fat depots, there was a significant increase in % small cells (14.9% vs 31.4%, p = 0 .006 and 14.0% vs 30.5%, p = 0 .015, respectively) and corresponding decrease in % large cells for nondiabetic vs diabetic patients. There was a similar trend for mesentery but it did not reach statistical significance (p = 0 .090). For omentum and mesentery, there was also a significant decrease in the diameter of the small cells. Fasting glucose was positively correlated with fraction of small cells in omentum and mesentery, and HbA 1C was positively correlated with fraction of small cells in the omental fat depot. There was no correlation between large cell diameter with clinical parameters in any of the fat depots.Conclusions/interpretation: These results indicate size distribution of adipocytes, specifically an increase in the fraction of small cells, is associated with the presence of type 2 diabetes mellitus.
No longer regarded as simply a storage depot, fat is a dynamic organ acting locally and systemically to modulate energy homeostasis, glucose sensitivity, insulin resistance, and inflammatory pathways. Here, mass spectrometry was used to survey the proteome of patient matched subcutaneous fat and visceral fat in 20 diabetic vs 22 nondiabetic patients with morbid obesity. A similar number of proteins (~600) were identified in each tissue type. When stratified by diabetic status, 19 and 41 proteins were found to be differentially abundant in subcutaneous fat and omentum, respectively. These proteins represent pathways known to be involved in metabolism. Five of these proteins were differentially abundant in both fat depots: moesin, 78 kDa glucose-regulated protein, protein cordon-bleu, zinc finger protein 611, and cytochrome c oxidase subunit 6B1. Three proteins, decorin, cytochrome c oxidase subunit 6B1, and 78 kDa glucose-regulated protein, were further tested for validation by western blot analysis. Investigation of the proteins reported here is expected to expand on the current knowledge of adipose tissue driven biochemistry in diabetes and obesity, with the ultimate goal of identifying clinical targets for the development of novel therapeutic interventions in the treatment of type 2 diabetes mellitus. To our knowledge, this study is the first to survey the global proteome derived from each subcutaneous and visceral adipose tissue obtained from the same patient in the clinical setting of morbid obesity, with and without diabetes. It is also the largest study of diabetic vs nondiabetic patients with 42 patients surveyed.
Chronic skin wound caused by diabetic disease is very common worldwide. Moreover, there is a shortage of effective curing technology in clinic. In this work, we developed a novel technology using thermosensitive hydrogel on wound top combined with insulin injection. The efficiency and mechanism of this technology were investigated in a diabetic mouse model. Dorsal-paired 8–10 mm diameter wounds were created in 12 mice. The wound healing rate was determined over a 28-day interval in healthy control (Control), control with diabetes (DControl), poloxamer treatment (Pox), and poloxamer plus insulin injection (Poxin) mice. Histological specimens were observed in all samples. Real-time quantitative polymerase chain reaction (qRT-PCR) was performed to measure the relative expression of α-smooth muscle actin (α-SMA) and transforming growth factor beta 1 (TGF-β1) in wound tissues at 7, 14, and 28 days. Compared with DControl animals, those treated with Poxin showed accelerated wound closure and healing rate (p < 0.05); expression of both α-SMA and TGF-β1 was significantly higher than that of the DControl and Pox animals during the first 7 days postoperation, but a significant decrease at day 14. Therefore, we concluded that hydrogel combined with insulin accelerated wound healing. Controlling the glucose level via insulin injection is more beneficial than hydrogel alone for healing chronic wounds, potentially through the increase of α-SMA and TGF-β1 expression in early phase.
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