We show that transplantation of adult bone marrow-derived cells expressing c-kit reduces hyperglycemia in mice with streptozotocin-induced pancreatic damage. Although quantitative analysis of the pancreas revealed a low frequency of donor insulin-positive cells, these cells were not present at the onset of blood glucose reduction. Instead, the majority of transplanted cells were localized to ductal and islet structures, and their presence was accompanied by a proliferation of recipient pancreatic cells that resulted in insulin production. The capacity of transplanted bone marrow-derived stem cells to initiate endogenous pancreatic tissue regeneration represents a previously unrecognized means by which these cells can contribute to the restoration of organ function.

There is increasing evidence that poor early growth confers an increased risk of type 2 diabetes, hypertension, and other features of the metabolic syndrome in later life. We hypothesized that this may result from poor nutrition during early life exerting permanent effects on the structure and function of key metabolic organ systems. To study the long-term impact of early-life undernutrition on susceptibility to visceral adiposity, we used a rat model of maternal protein restriction (MPR) in which dams were fed a lowprotein diet (containing 8% instead of 20% protein in control diet) throughout pregnancy and lactation. MPR offspring were born smaller than controls (offspring of dams on control diet) and in adulthood developed visceral adiposity. We compared the pattern of gene expression in visceral adipose tissue (VAT) between MPR offspring and controls with Affymetrix rat expression arrays. Of the total number of genes and expressed sequence tags analyzed (15,923 probe sets), 9,790 (61.5%) were expressed in VAT. We identified 650 transcripts as differentially expressed Ն1.5-fold in the VAT of MPR offspring. Gene ontology analysis revealed a global upregulation of genes involved in carbohydrate, lipid, and protein metabolism. A number of genes involved in adipocyte differentiation, angiogenesis, and extracellular matrix remodeling were also upregulated. However, in marked contrast to other rodent models of obesity, the expression of a large number of genes associated with inflammation was reduced in this rat model. Thus visceral adiposity in this early-life programmed rat model is marked by dynamic changes in the transcriptional profile of VAT. Our data provide new insights into the molecular mechanisms that underlie the early-life programming of visceral adiposity.visceral adipose tissue; maternal protein restriction; DNA microarray OBESITY IS A SERIOUS MEDICAL PROBLEM not only because it substantially impairs quality of life but also because it increases the risk of hypertension, type 2 diabetes, coronary heart disease, sleeping disorders, and cancers (43). There is strong evidence for a genetic component to human obesity (28). Multiple systems regulate energy homeostasis (35,44), and a number of genes associated with human obesity have been identified (19), yet the genetic component of this condition cannot explain the dramatic increase in the prevalence of obesity in recent years.A large number of epidemiological studies have revealed a strong statistical association between poor fetal growth and the subsequent development of type 2 diabetes, hypertension, and obesity, visceral obesity in particular (54). These observations were made initially by Barker et al. in England (3a) but have now been reproduced in a large number of populations worldwide. These findings have led to the "fetal origins" hypothesis, which states that an adverse intrauterine environment programs or imprints the development of fetal tissues, permanently determining physiological responses and ultimately producing dysfunction and disease ...

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