Highlights From the Latest in Diabetes Research

The growing impact of the obesity epidemic promises that type 2 diabetes will remain a public health burden well into the future. Novel therapeutic strategies aimed at reducing diabetes risk are badly needed, and ones that focus on adipose tissue (AT) may be particularly useful because of the central role that this tissue plays in diabetes risk. It has been demonstrated that when macrophages gain access to AT and become activated, they secrete infl ammatory cytokines that create a chronic state of infl ammation. It has also been suggested that this state of ongoing infl ammation increases diabetes risk. Indeed, an inverse association has been shown between macrophage numbers in visceral AT and insulin sensitivity. However, although there is a great deal of evidence supporting the idea that abnormalities of glucose metabolism result—at least in part—from chronic infl ammation in AT, data that refl ect a direct observation of this connection are absent from the literature. The reason for this gap is rather simple: It has not been possible to manipulate the expression of macrophage infl ammatory genes in AT without impacting the expression of these genes in other tissues. Direct evidence of the role of AT-associated infl ammation in glucose regulation could be demonstrated if there were a method to ablate these genes only in AT macrophages and relate this to improved glucose tolerance. A new study by Aouadi et al. not only shows a novel technique for silencing genes specifi cally in AT macrophages, it also demonstrates that obese mice whose tumor necrosis factor-α (TNF-α) and osteopontin were silenced in epididymal AT macrophages experienced improved glucose tolerance. The investigators injected glucan-encapsulated small interfering RNA particles (GeRPs) into obese mice and observed that they accumulated primarily in the AT but not in other tissues such as heart, liver, spleen, pancreas, lung, or kidney. Additional experiments indicated the injection of GeRPs resulted in signifi cant depletion of TNF-α and osteopontin and an accompanying improvement in glucose tolerance. These intriguing fi ndings support a direct role for AT infl ammation in glucose dysregulation and suggest a potential application of gene-targeted therapy to improve insulin sensitivity. — Helaine E. Resnick, PhD, MPH