Myokines:metabolic regulation in obesity and type 2 diabetes

Skeletal muscle plays a vital role in the regulation of systemic metabolism,partly through its secretion of endocrine factors which are collectively known as myokines.Altered myokine levels are associated with metabolic diseases,such as type 2 diabetes(T2D).The significance of interorgan crosstalk,particularly through myokines,has emerged as a fundamental aspect of nutrient and energy homeostasis.However,a comprehensive understanding of myokine biology in the setting of obesity and T2D remains a major challenge.In this review,we discuss the regulation and biological functions of key myokines that have been extensively studied during the past two decades,namely interleukin 6(IL-6),irisin,myostatin(MSTN),growth differentiation factor 11(GDF11),fibroblast growth factor 21(FGF21),apelin,brain-derived neurotrophic factor(BDNF),meteorin-like(Metrnl),secreted protein acidic and rich in cysteine(SPARC),β-aminoisobutyric acid(BAIBA),Musclin,and Dickkopf 3(Dkk3).Related to these,we detail the role of exercise in myokine expression and secretion together with their contributions to metabolic physiology and disease.Despite significant advancements in myokine research,many myokines remain challenging to measure accurately and investigate thoroughly.Hence,new research techniques and detection methods should be developed and rigorously tested.Therefore,developing a comprehensive perspective on myokine biology is crucial,as this will likely offer new insights into the pathophysiological mechanisms underlying obesity and T2D and may reveal novel targets for therapeutic interventions.

β-cell dynamics in type 2 diabetes and in dietary and exercise interventions

Pancreaticβ-cell dysfunction and insulin resistance are two of the major causes of type 2 diabetes(T2D).Recent clinical and experimental studies have suggested that the functional capacity ofβ-cells,particularly in the first phase of insulin secretion,is a primary contributor to the progression of T2D and its associated complications.Pancreaticβ-cells undergo dynamic compensation and decompensation processes during the development of T2D,in which metabolic stresses such as endoplasmic reticulum stress,oxidative stress,and inflammatory signals are key regulators ofβ-cell dynamics.Dietary and exercise interventions have been shown to be effective approaches for the treatment of obesity and T2D,especially in the early stages.Whilst the targeted tissues and underlying mechanisms of dietary and exercise interventions remain somewhat vague,accumulating evidence has implicated the improvement ofβ-cell functional capacity.In this review,we summarize recent advances in the understanding of the dynamic adaptations ofβ-cell function in T2D progression and clarify the effects and mechanisms of dietary and exercise interventions onβ-cell dysfunction in T2D.This review provides molecular insights into the therapeutic effects of dietary and exercise interventions on T2D,and more importantly,it paves the way for future research on the related underlying mechanisms for developing precision prevention and treatment of T2D.