Introduction

Diabetes mellitus(DM)is a global chronic metabolic disease characterized by high blood glucose concentration.Diabetic patients exhibit either insulin deficiency due toβcell failure or insulin resistance where the body lacks a normal response to insulin［1］.The pancreaticβ-cell plays an important role in diabetes pathology because it produces insulin.Both typeⅠdiabetes mellitus(T1DM)and typeⅡdiabetes mellitus(T2DM)are characterized by progressiveβ-cell failure［2］.In T1DM，β-cell failure is typically caused by viral infections or cytokines，such as interleukin-1β-(IL-1β)and interferon-γ(IFNγ)，that induce a progressive autoimmune assault againstβ-cells［3］.The pathogenesis of T2DM is more variable because of the different degrees ofβ-cell failure and insulin resistance［4］.Apoptosis is the primary form ofβ-cell death in both types of DM［2］.That high blood glucose concentration is the most significant characteristic of diabetic patients［5］is supported by diabetic models establishing that glucose toxicity as a contributor to the development of insulin resistance，impaired insulin secretion and pancreaticβ-cell failure［6］.

Autophagy，a conserved intracellular，self-protective mechanism under stressful conditions，is necessary to maintain the architecture and function of mammalian cells［7］.Through a lysosomal degradation pathway，autophagy helps host cells degrade longevity proteins，damaged mitochondria and other aging orto produce small molecules of organic matter(e.g.amino acids)to ensure the survival of cells and maintain cell homeostasis［8］.Autophagy is either positively mediated bythe adenosine 5＇-monophosphate(AMP)-activated protein kinase(AMPK)pathway［9］，or negatively mediated by the mammalian target of rapamycin(mTOR)pathway.(https://www.daowen.com)

The cross-talk between autophagy and apoptosis is complex［10］.Notably，numerous death stimuli are capable of activating either the autophagy or apoptosis and several genes that are critical for execution of their respective pathway can function in the other pathway.In addition，the autophagy and apoptosis pathways share common regulator and components，and can positively or negatively regulate and modify each other［11］.Thus，the exact relationship between autophagy and apoptosis depends on specific conditions.

Xiaokeping(National Medicine Approved No.Z44020069)，a commercially avaliable TCM that is licenced by China Food and Drug Administration(CFDA)，has been used in the clinical treatment of T2DM in China for many years［12］.Xiaokeping consists of 12 Chinese medicinal herbs：Ginseng radix(1.08%)，Coptidis rhizoma(1.08%)，Trichosanthis radix(26.88%)，Asparagi radix(2.72%)，Astragali radix(26.88%)，Salviae miltiorrhizae radix et rhizoma(8.03%)，Lycii fructus(6.45%)，Astragali complanati pollen(8.03%)，Puerariae lobatae radix(8.03%)，Anemarrhenae rhizoma(5.38%)，Galla chinensis(2.72%)，and Schisandrae chinensis fructus(2.72%).It contains numerous chemicals such as alkaloids，flavonoids，quinones，triterpene glycosides，and organic acids.Studies have reported that XKP can inhibit diabetic nephropathy in streptozotocin-induced rats by blocking signaling of transforming growth factor-β1(TGF-β1)/similar mothers against decapentaplegic homolog 7(Smad7)［13］.However，the molecular mechanism of XKP underlying its effects in clinical treatment of T2DM is not clear and the interaction between autophagy and apoptosis in relation to pancreaticβ-cells under high glucose stress is unknown.The objective of the present study was to investigate potential mechanisms of XKP in diabetes therapy for secondary development of XKP.