Maturity-onset diabetes of the young (MODY)is a heterogeneous monogenic diabetes, in which MODY1, MODY2, and MODY3 are the most common subtypes. In recent years, new hypoglycemic drugs such as glucagon-like peptide-1 receptor agonists (GLP-1RA), dipeptidyl peptidase-4 inhibitors (DPP-4i), sodium-glucose co-transporter 2 inhibitors (SGLT2i), and glucokinase activators (GKA)have made good progress in the treatment of diabetes. Based on the latest basic and clinical evidence, the article reviews the pathogenesis, clinical features, diagnosis and treatment progress of new hypoglycemic drugs of the above three types of MODY, aiming to develop safer and more effective new ways for the diagnosis and treatment of MODY.

AIM:To investigate the effects of cannabinoid receptor agonist WIN55212-2(WIN)on acute lung injury(ALI)in septic mice,and to explore its potential mechanisms through glycolysis.METHODS:A mouse model of septic ALI was established by intraperitoneal injections of lipopolysaccharide(LPS).Male C57BL/6J mice were randomly divided into 4 groups(n=6):(1)control group;(2)LPS group,receiving intraperitoneal injections of LPS at 10 mg/kg;(3)LPS+WIN group,receiving 1 mg/kg WIN intraperitoneally 30 min prior to LPS injection;(4)LPS+WIN+MHY1485[mammalian target of rapamycin(mTOR)activator]group,receiving 10 mg/kg MHY1485 intraperitoneally 1 d before LPS injection and 1 mg/kg WIN plus 10 mg/kg MHY1485 30 min before LPS injection.Tissues were collected 24 h after modeling for analysis.Lung indexes were calculated,and histopathological changes of lung tissues were observed via he-matoxylin-eosin(HE)staining.Inflammatory cytokines interleukin-1β(IL-1β)and IL-10 in lung tissues,and lactic acid and lactate dehydrogenase A(LDHA)in serum were quantified using ELISA.The levels of mTOR/hypoxia-inducible fac-tor-1α(HIF-1α)/6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3(PFKFB3)signaling pathway-related proteins were assessed by Western blot.RESULTS:Compared with control group,the LPS group exhibited an increased lung in-dex,significant lung tissue damage,an increase in IL-1β levels(P＜0.05),a decrease in IL-10 levels(P＜0.05),and el-evated expressions of lactate and LDHA(P＜0.05),along with increased levels of phosphorylated mTOR(p-mTOR),HIF-1α and PFKFB3 proteins(P＜0.05).The LPS+WIN group showed improvements with a reduced lung index(P＜0.05),lessened lung injury,decreased IL-1β levels(P＜0.05),increased IL-10 levels(P＜0.05),and lower levels of lactic acid,LDHA,p-mTOR,HIF-1α,and PFKFB3(P＜0.05).Conversely,the LPS+WIN+MHY1485 group displayed increased lung indexes and lung tissue damage,elevated IL-1β levels(P＜0.05),reduced IL-10 levels(P＜0.05),and higher expressions of lactic acid,LDHA,p-mTOR,HIF-1α and PFKFB3(P＜0.05)compared to the LPS+WIN group.CONCLUSION:WIN55212-2 mitigates sepsis-induced ALI,potentially by modulating the mTOR/HIF-1α/PFKFB3 sig-naling pathway,thereby inhibiting glycolysis and alleviating inflammatory responses.

Objective To investigate the effects of cannabinoid receptor agonist,WIN55212-2(WIN),on acute kidney injury(AKI)in mice with sepsis and its underlying mechanism.Methods Twenty-four healthy male mice were divided into(n=6):Control group,sepsis group(LPS group),sepsis+WIN55212-2 group(LPS+WIN group)and sepsis+WIN55212-2+mTOR activator MHY1485 group(LPS+WIN+MHY group).The sepsis model was constructed by intraperitoneal injection of LPS.After the tissue and blood samples were harvested in 24 h after modeling,ELISA was used to determine the contents of IL-1β,IL-18 and lactate dehydrogenase A(LDHA)in the renal tissues,as well as Scr,kidney injury molecule-1(KIM-1)and lactic acid(LA)in the serum.HE staining was employed to observe the pathological changes of kidney tissue and Paller score was calculated.The expression of p-AKT,p-Mtor and 6-phosphofructokinase-2/fructose-2,6-biphosphatase 3(PFKFB3)in the renal tissues was detected by Western blotting.Results Compared with the Control group,the LPS group had obvious kidney tissue damage,increased Paller score(P＜0.05),increased serum contents of lactic acid,Scr and KIM-1(P＜0.05),up-regulated contents of LDHA,IL-1β and IL-18 in the renal tissues(P＜0.05),and elevated expression levels of p-AKT,p-Mtor and PFKFB3 in the renal tissues(P＜0.05).Milder pathological injury in kidney tissue,decreased Paller score(P＜0.05),reduced contents of lactic acid,Scr and KIM-1(P＜0.05),decreased contents of LDHA,IL-1β and IL-18(P＜0.05),and lower expression of p-AKT,p-Mtor and PFKFB3 were observed in the LPS+WIN group than the LPS group(P＜0.05).The LPS+WIN+MHY group had notably higher Paller score(P＜0.05),raised contents of lactic acid,Scr and KIM-1(P＜0.05),increased contents of LDHA,IL-1β and IL-18(P＜0.05),and up-regulated expression of p-AKT,p-Mtor and PFKFB3(P＜0.05)when compared with the LPS+WIN group.Conclusion WIN can alleviate AKI in sepsis,and it may reduce the level of glycolysis in renal tissue,and alleviate inflammation through inhibiting AKT/Mtor/PFKFB3 signaling pathway.

The impairment of islets β cell by autoimmune response is an important cause of type 1 diabetes mellitus (T1DM). Some monogenic autoimmune syndromes could induce T1DM in difference chance, which are important disease models to deeply understand autoimmunity and T1DM. This article reviews the diagnosis, treatment and genetic detection of eight known single gene autoimmune syndromes associated with T1DM, arming to expand the diagnosis and treatment of T1DM.