An adipoincretin effect links adipostasis with insulin secretion.

The current model for the insulin system focuses excessively on the interplay between insulin and blood glucose, and could be called a 'glucosestat'. The response of insulin to feeding is mainly governed by the glucoincretin effect, which depends on the secretion of glucoincretins, which is not specific to glucose. The insulin system during fasting is governed by the adipoincretin effect, which operates as a feedback control system governed by adipocyte phosphoinositide-3 kinase (PI3K) signaling. Under fasting conditions, the insulin system behaves as a 'cruise control' system for lipolysis, which can be described as an 'adipostat'. The current paradigm for the insulin system focuses on the phenomenon of glucose-stimulated insulin secretion and insulin action on blood glucose control. This historical glucose-centric perspective may have introduced a conceptual bias in our understanding of insulin regulation. A body of evidence demonstrating that in vivo variations in blood glucose and insulin secretion can be largely dissociated motivated us to reconsider the fundamental design of the insulin system as a control system for metabolic homeostasis. Here, we propose that a minimal glucose-centric model does not accurately describe the physiological behavior of the insulin system and propose a new paradigm focusing on the effects of incretins, arguing that under fasting conditions, insulin is regulated by an adipoincretin effect. The current paradigm for the insulin system focuses on the phenomenon of glucose-stimulated insulin secretion and insulin action on blood glucose control. This historical glucose-centric perspective may have introduced a conceptual bias in our understanding of insulin regulation. A body of evidence demonstrating that in vivo variations in blood glucose and insulin secretion can be largely dissociated motivated us to reconsider the fundamental design of the insulin system as a control system for metabolic homeostasis. Here, we propose that a minimal glucose-centric model does not accurately describe the physiological behavior of the insulin system and propose a new paradigm focusing on the effects of incretin, arguing that under fasting conditions, insulin is regulated by an adipoincretin effect. [ABSTRACT FROM AUTHOR]