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.
Highlights
Diabetes is a chronic, metabolic disease characterized by elevated levels of blood glucose, which leads over time to serious damage to the heart, blood vessels, eyes, kidneys and nerves according to World health Organization [1]
We focus on previously published literature about the physiological or pathological activities of cyclic adenosine monophosphate (cAMP) in different organs related to diabetes, including pancreatic islets, liver, gut, skeletal muscle, adipose tissues, brain, and kidney, and discuss the dietary bioactive ingredients which regulate glucose homeostasis by targeting cAMP
Oleic acid, monounsaturated long chain fatty acids, modulates the rates of fatty acid oxidation, ameliorates insulin resistance, and decreases inflammation in skeletal muscle cells and Wistar rats via stimulating the cAMP/protein kinase A (PKA) pathway, respectively [92,93]. These genetic and pharmacological studies have shown that appropriately regulated cAMP/PKA activity is essential for skeletal muscle glucose uptake and systemic glucose homeostasis
Summary
Metabolic disease characterized by elevated levels of blood glucose (or blood sugar), which leads over time to serious damage to the heart, blood vessels, eyes, kidneys and nerves according to World health Organization [1]. Hepatic glucose production is increased by glucagon, inhibited by insulin, and regulated by neural signals from the brain. Cyclic adenosine monophosphate (cAMP), a vital intracellular second messenger, is synthesized from adenosine triphosphate (ATP) by adenylyl cyclase (Adcy) and degraded by phosphodiesterase (PDE) It exerts various physiological effects by activating protein kinase A (PKA), the classical cAMP downstream effector. Accumulated evidence has demonstrated that various food-derived bioactive ingredients perform excellent pharmacological roles for diabetes prevention and treatment via targeting cAMP signaling pathway. We focus on previously published literature about the physiological or pathological activities of cAMP in different organs related to diabetes, including pancreatic islets, liver, gut, skeletal muscle, adipose tissues, brain, and kidney, and discuss the dietary bioactive ingredients which regulate glucose homeostasis by targeting cAMP. We hope that the conclusion of this review provides a new strategy for the prevention and treatment of diabetes
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