Dietary Bioactive Ingredients Modulating the cAMP Signaling in Diabetes Treatment

Abstract

As the prevalence of diabetes increases progressively, research to develop new therapeutic approaches and the search for more bioactive compounds are attracting more attention. Over the past decades, studies have suggested that cyclic adenosine monophosphate (cAMP), the important intracellular second messenger, is a key regulator of metabolism and glucose homeostasis in diverse physiopathological states in multiple organs including the pancreas, liver, gut, skeletal muscle, adipose tissues, brain, and kidney. The multiple characteristics of dietary compounds and their favorable influence on diabetes pathogenesis, as well as their intersections with the cAMP signaling pathway, indicate that these compounds have a beneficial effect on the regulation of glucose homeostasis. In this review, we outline the current understanding of the diverse functions of cAMP in different organs involved in glucose homeostasis and show that a diversity of bioactive ingredients from foods activate or inhibit cAMP signaling, resulting in the improvement of the diabetic pathophysiological process. It aims to highlight the diabetes-preventative or -therapeutic potential of dietary bioactive ingredients targeting cAMP signaling.

Keywords: cAMP; diabetes; dietary bioactive ingredients; glucose homeostasis.

Figure 1

Coordination of various organs is required in the regulations of glucose homeostasis.

Figure 2

Schematic illustration of cAMP signaling pathway. Adcy: adenylyl cyclase; ATP: adenosine triphosphate; Epac: exchange proteins directly activated by cAMP; CREB: cAMP-response element binding protein; PDE: phosphodiesterase; PKA: protein kinase A.

Figure 3

cAMP signaling pathway in the regulation of glucose homeostasis in pancreatic β cells (a) and hepatocytes (b). Adcy: adenylyl cyclase; ATP: adenosine triphosphate; Epac: exchange proteins directly activated by cAMP; CREB: cAMP-response element binding protein; G6pase: glucose-6-phosphatase; PDE: phosphodiesterase; PEPCK: phosphoenolpyruvate carboxykinase; PKA: protein kinase A; MPC: mitochondrial pyruvate carrier.