The islet of Langerhans, often termed the pancreatic islet, is a discrete endocrine organ that secretes multiple hormones which together orchestrate human energy metabolism. Maintenance of an appropriate functional islet mass is necessary for whole-body glucose homeostasis. As with other metabolic tissues, growth factors are key regulators of islet development, maintenance, and adaptive responses.
Among these growth factors, insulin and insulin-like growth factors (IGFs) have emerged as central players in modulating islet cell fate and function. A large and expanding literature supports roles for insulin/IGF signaling in multiple aspects of islet biology, and perturbations in this pathway are increasingly recognized as characteristic features of type 2 diabetes pathophysiology.
A substantial body of evidence summarized in the source positions insulin/IGF signaling as instrumental in regulating diverse cellular processes within islets. Much of the recent focus has been on β-cells, given their central role in insulin secretion and glucose regulation, but insulin and IGFs influence other islet cell types and intercellular interactions as well.
The review outlines how insulin and IGFs contribute to the maintenance of functional islet mass and to the regulation of cellular programs that preserve or modify insulin secretory capacity. Dysregulated signaling through insulin and IGF pathways has been linked with impaired islet function and to the metabolic disturbances seen in type 2 diabetes. The source frames these pathways as both physiological regulators and as potential targets for therapeutic strategies aimed at preserving or restoring islet health.
Recent reports covered in the review highlight several emerging mechanistic themes in insulin/IGF action within islets. One area of interest is the role of RNA modifications in the control of islet cell behavior; these post-transcriptional mechanisms are implicated in mediating aspects of insulin/IGF signaling in β-cells.
Another notable development is recognition of transcriptional regulation mediated by nuclear insulin and IGF-1 receptors. Rather than acting solely at the cell surface to trigger cytosolic signaling cascades, insulin and IGF-1 receptors can influence nuclear events and gene expression programs relevant to islet cell function.
Additionally, the review reports the discovery of an insulin inhibitory receptor called inceptor. Inceptor has been described as a modulator of insulin signaling in islets, representing a newly identified component that can attenuate insulin receptor pathway activity. The review presents these findings as part of an evolving mechanistic framework that refines understanding of how insulin/IGF signaling is executed and regulated in pancreatic islet cells.
The review summarizes available evidence on the effects of exogenous insulin therapy in humans, distinguishing between short-term and long-term outcomes on islet biology. Insulin treatment is considered both for its systemic glucose-lowering actions and for its potential direct or indirect effects on islet cells.
Specifics regarding the magnitude of these effects, their time course, or comparative outcomes were not detailed in the abstract; the review indicates that recent studies have addressed how insulin therapy interacts with endogenous islet signaling pathways and may influence islet cell function and mass over varying durations of treatment. The review also situates insulin therapy within broader therapeutic contexts, including interactions with incretin pathways and other modulators of islet biology.
Based on the summarized mechanisms and clinical observations, the authors propose potential strategies to maximize beneficial insulin action in islets as an approach to counter diabetes. These strategies are framed around leveraging knowledge of insulin/IGF signaling, the newly described regulatory elements (such as inceptor), and emerging molecular mechanisms (including RNA modifications and nuclear receptor actions).
The review emphasizes the translational potential of targeting islet-specific components of insulin/IGF pathways to preserve or restore β-cell function. It also highlights the broader therapeutic context, noting interplay with incretins and other systemic regulators of glucose metabolism.
The source concludes that insulin and IGFs play central roles in islet cell biology and that dysregulation of these pathways is a hallmark of type 2 diabetes. Recent discoveries — including roles for RNA modifications, nuclear insulin/IGF-1 receptor–mediated transcriptional regulation, and the identification of the inhibitory receptor inceptor — expand the conceptual framework for how insulin/IGF signaling operates in islets.
The review presents both a synthesis of current functional knowledge and considerations for future therapeutic strategies aimed at enhancing beneficial insulin action within islets to combat diabetes. For full experimental details, data, and specific therapeutic proposals, readers are directed to the complete article (Endocr Rev. 2026;47(5):637–665; PMID 42159041; DOI 10.1210/endrev/bnag014).