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Insulin signaling is a conserved feature in all metazoans. It evolved with the appearance of multicellularity, allowing primordial metazoans to respond to a greater diversity of environmental signals. The insulin signaling pathway is highly conserved in insects and particularly in Drosophila, where it has been extensively studied in recent years and shown to control metabolism, growth, reproduction, and longevity. Because misregulation of the insulin/IGF pathway in humans plays a role in many medical disorders, such as diabetes and various types of cancer, unraveling the regulation of insulin/IGF signaling using the power of a genetically tractable organism like Drosophila may contribute to the amelioration of these major human pathologies., Extensive study of mammalian insulin/IGF biology has established that the insulin/IGF system (IIS) is split into two complementary and interacting subsystems that govern growth, metabolism, reproduction, and longevity (1). Insulin, [...]

Multicellular organisms have evolved organs and tissues with highly specialized tasks. For instance, nutrients are assimilated by the gut, sensed, processed, stored, and released by adipose tissues and liver to provide energy consumed by peripheral organ activities. The function of each organ is modified by local clues and systemic signals derived from other organs to ensure a coordinated response accommodating the physiological needs of the organism. The intestine, which represents one of the largest interfaces between the internal and external environment, plays a key role in sensing and relaying environmental inputs such as nutrients and microbial derivatives to other organs to produce systemic responses. In turn, gut physiology and immunity are regulated by multiple signals emanating from other organs including the brain and the adipose tissues. In this review, we highlight physiological processes where the gut serves as a key organ in coupling systemic signals or environmental cues with organism growth, metabolism, immune activity, aging, or behavior. Robust strategies involving intraorgan and interorgan signaling pathways have evolved to preserve gut size in homeostatic conditions and restrict growth during damage‐induced regenerative phases. Here we review some of the mechanisms that maintain gut size homeostasis and point out known examples of homeostasis‐breaking events that promote gut plasticity to accommodate changes in the external or internal environment. This article is categorized under: Adult Stem Cells, Tissue Renewal, and Regeneration > Tissue Stem Cells and Niches Adult Stem Cells, Tissue Renewal, and Regeneration > Environmental Control of Stem Cells Adult Stem Cells, Tissue Renewal, and Regeneration > Regeneration The gut plays a key role in relaying environmental cues to other organs to trigger adaptive responses.

Comment on: Colombani J, et al. Science 2012; 336:582-5.