Glucose Metabolism Disorders Research Articles

Glucose metabolism disorders in cancer patients

Glucose metabolism disorders in cancer patients

Understanding COVID-19 progression with longitudinal peripheral blood mononuclear cell proteomics: Changes in the cellular proteome over time

The clinical presentation of COVID-19 is highly variable, and understanding the underlying biological processes is crucial. This study utilized a proteomic analysis to investigate dysregulated processes in the peripheral blood mononuclear cells of patients with COVID-19 compared to healthy volunteers. Samples were collected at different stages of the disease, including hospital admission, after 7days of hospitalization, and 30days after discharge. Metabolic pathway alterations and increased abundance of neutrophil-related proteins were observed in patients. Patients progressing to critical illness had significantly low-abundance proteins in the pentose phosphate and glycolysis pathways compared with those presenting clinical recovery. Important biological processes, such as fatty acid concentration and glucose metabolism disorder, remained altered even after 30days of hospital discharge. Temporal proteomic changes revealed distinct pathways in critically ill and non-critically ill patients. Our study emphasizes the significance of longitudinal cellular proteomic studies in identifying disease progression-related pathways and persistent protein changes post-hospitalization.

Microbiome and metabolome dysbiosis analysis in impaired glucose tolerance for the prediction of progression to diabetes mellitus

Gut microbiota and circulating metabolite dysbiosis predate important pathological changes in glucose metabolic disorders; however, comprehensive studies on impaired glucose tolerance (IGT), a diabetes mellitus (DM) precursor, are lacking. Here, we perform metagenomic sequencing and metabolomics on 47 pairs of individuals with IGT and newly diagnosed DM and 46 controls with normal glucose tolerance (NGT); patients with IGT are followed up after 4 years for progression to DM. Analysis of baseline data reveals significant differences in gut microbiota and serum metabolites among the IGT, DM, and NGT groups. In addition, 13 types of gut microbiota and 17 types of circulating metabolites showed significant differences at baseline before IGT progressed to DM, including higher levels of Eggerthella unclassified, Coprobacillus unclassified, Clostridium ramosum, L-valine, L-norleucine, and L-isoleucine, and lower levels of Eubacterium eligens, Bacteroides faecis, Lachnospiraceae bacterium 3_1_46FAA, Alistipes senegalensis, Megaspaera elsdenii, Clostridium perfringens, α-linolenic acid, 10E,12Z-octadecadienoic acid, and dodecanoic acid. A random forest model based on differential intestinal microbiota and circulating metabolites can predict the progression from IGT to DM (AUC = 0.87). These results suggest that microbiome and metabolome dysbiosis occur in individuals with IGT and have important predictive values and potential for intervention in preventing IGT from progressing to DM.

Micro-Executor of Natural Products in Metabolic Diseases.

Obesity, diabetes, and cardiovascular diseases are the major chronic metabolic diseases that threaten human health. In order to combat these epidemics, there remains a desperate need for effective, safe, and easily available therapeutic strategies. Recently, the development of natural product research has provided new methods and options for these diseases. Numerous studies have demonstrated that microRNAs (miRNAs) are key regulators of metabolic diseases, and natural products can improve lipid and glucose metabolism disorders and cardiovascular diseases by regulating the expression of miRNAs. In this review, we present the recent advances involving the associations between miRNAs and natural products and the current evidence showing the positive effects of miRNAs for natural product treatment in metabolic diseases. We also encourage further research to address the relationship between miRNAs and natural products under physiological and pathological conditions, thus leading to stronger support for drug development from natural products in the future.

Progress and indication for use of continuous glucose monitoring in patients with diabetes in pregnancy: a review.

Gestational diabetes mellitus is one of the most common endocrine diseases that occur during pregnancy. Disorders of blood glucose metabolism during pregnancy can increase the risk of adverse pregnancy outcomes, such as pregnancy-related hypertension, preeclampsia, eclampsia, miscarriage, macrosomia, and neonatal hypoglycemia. Continuous glucose monitoring (CGM) can safely and effectively monitor blood glucose changes in patients with gestational hyperglycemia, thereby reducing adverse pregnancy outcomes. Hence, this article aimed to provide a comprehensive review of the progress and indications for using CGM in pregnant patients with diabetes. CGM can reduce blood glucose fluctuations and the occurrence of serious hypoglycemia and hyperglycemia events and can provide time in range (TIR). TIR is an important indicator of blood glucose level. Patients with a higher TIR during pregnancy have better gestational outcomes.

Association of Glycosylated Hemoglobin Levels with Insulin Resistance in Adolescent among Medical Students Ain Shams University

Abstract Background Insulin resistance is a common pathway for the development of glucose metabolism disorders and high blood pressure, all of which are components of the metabolic syndrome. The earlier onset of obesity may cause a longer period of insulin resistance, which may explain the concomitant earlier onset of impaired glucose tolerance in young obese people and adolescents so insulin resistance has been implicated as risk factor for metabolic disorders and it is of real importance to develop simple test that can be used in routine clinical setting for identifying insulin resistant individuals in advance so HOMA-IR(Homeostatic Model Assessment for Insulin Resistance) and HbA1c (glycated haemoglobin) screening to identify young at high risk for insulin resistance and diabetes at an early stage. The study aimed to evaluate the association of HOMA-IR (Homeostatic Model Assessment of Insulin Resistance) and HbA1c levels in overweight and nonoverweight young medical students to assess insulin resistance, a condition that can cause diabetes mellitus and metabolic syndrome in earlier life. Subject and Methods The study was systematic random sample was conducted between 40 overweight and 40 non-overweight students (80 in total). All cases were subjected to history taking, clinical examination and laboratory investigations included HOMA-IR and HbA1c. Results Regarding HOMA-IR in present study they illustrated statistically significant difference between groups with higher levels in overweighed group than for normal weight group.HOMA-IR ≥2.5 was represent (17.5%)of normal weight group and (45.0%) of overweighed group with statistically significant difference. N statistically significant difference regarding Glucose (mg/dl) level for normal and overweighed group. The relation was statistically significant regarding Insulin (mIU/ml) level as it was higher in overweighed group than normal group. Regarding HbA1c% in present study; there is no statistically significant difference between normal group compared to obese group that range within normal values with higher result in obese group. Our study found statistically significant association between HOMA-IR<2.5 and (glucose and insulin), in both groups and for HbA1c in obese group. Also statistically significant positive correlation between HOMA-IR and HbA1c% in all patients. Conclusion Obesity is significantly associated with higher levels of fasting insulin, and HOMA-IR values in adolescents. There is a positive correlation between HbA1c and HOMA-IR

Appendicular Skeletal Muscle Mass Index Level (ASMI) and Its Influencing Factors in Healthy Adult Males.

We aimed to retrospectively analyze the level of appendicular skeletal muscle mass index (ASMI) in adult males and its influencing factors for early screening and intervention of sarcopenia. From January 2020 to December 2021, adult male medical examiners from the Health Management Center of the Affiliated Hospital of North Sichuan Medical College, Chengdu City, China were selected as the research subjects. The ASMI level was measured by bioelectrical impedance (BIA) method. The subjects were divided into four groups according to the quartiles of ASMI level, the levels of related indicators between the groups were compared, and the related factors affecting the ASMI level were analyzed. The detection rate of sarcopenia was about 1.09% (78/7187). One-way ANOVA or nonparametric test results showed that age, BMI, WHR, SBP, DBP, FPG, HbA1c, AST, ALT, GGT, Cr, UA, TG, TC, HDLC, LDL-C and FT3 levels were significantly different among the four ASMI groups (P<0.05). ASMI was positively correlated with BMI, WHR, SBP, DBP, FPG, HbA1c, AST, ALT, GGT, Cr, UA, TG, TC, LDL-C, FT3, and TSH (all P<0.05); negatively correlated with age and HDL-C (all P<0.05). Age, WHR and TG were independent risk factors for ASMI level, and BMI was an independent protective factor for ASMI level. The ASMI level in healthy adult males is related to age, obesity, blood pressure, glucose and lipid metabolism disorder, inflammation and thyroid hormone, among which age, BMI, WHR and TG are independent influencing factors of ASMI level.

Dysglycemia and arrhythmias.

Disorders in glucose metabolism can be divided into three separate but interrelated domains, namely hyperglycemia, hypoglycemia, and glycemic variability. Intensive glycemic control in patients with diabetes might increase the risk of hypoglycemic incidents and glucose fluctuations. These three dysglycemic states occur not only amongst patients with diabetes, but are frequently present in other clinical settings, such as during critically ill. A growing body of evidence has focused on the relationships between these dysglycemic domains with cardiac arrhythmias, including supraventricular arrhythmias (primarily atrial fibrillation), ventricular arrhythmias (malignant ventricular arrhythmias and QT interval prolongation), and bradyarrhythmias (bradycardia and heart block). Different mechanisms by which these dysglycemic states might provoke cardiac arr-hythmias have been identified in experimental studies. A customized glycemic control strategy to minimize the risk of hyperglycemia, hypoglycemia and glucose variability is of the utmost importance in order to mitigate the risk of cardiac arrhythmias.

Former long-term use of combined hormonal contraception and glucose metabolism disorders in perimenopausal women: A prospective, population-based cohort study.

Current use of combined hormonal contraceptives worsens glucose tolerance and increases the risk of type 2 diabetes mellitus at late fertile age, but the impact of their former use on the risk of glucose metabolism disorders is still controversial. This was a prospective, longitudinal birth cohort study with long-term follow-up consisting of 5889 women. The cohort population has been followed at birth, and at ages of 1, 14, 31 and 46. In total, 3280 (55.7%) women were clinically examined and 2780 also underwent a 2-h oral glucose tolerance test at age 46. Glucose metabolism indices were analyzed in former combined hormonal contraceptive users (n = 1371) and former progestin-only contraceptive users (n = 52) and in women with no history of hormonal contraceptive use (n = 253). Compared with women with no history of hormonal contraceptive use, those who formerly used combined hormonal contraceptives for over 10 years had an increased risk of prediabetes (odds ratio [OR] 3.9, 95% confidence interval [CI]: 1.6-9.2) but not of type 2 diabetes mellitus. Former progestin-only contraceptive use was not associated with any glucose metabolism disorders. The results persisted after adjusting for socioeconomic status, smoking, alcohol consumption, parity, body mass index and use of cholesterol-lowering medication. Former long-term use of combined hormonal contraceptives was associated with a significantly increased risk of prediabetes in perimenopausal women, which potentially indicates a need of screening for glucose metabolism disorders in these women.

Haloxyfop-P-methyl induces immunotoxicity and glucose metabolism disorders and affects the Nrf2/ARE pathway mediated antioxidant system in Chiromantes dehaani

Haloxyfop-P-methyl is used extensively in agricultural production, and its metabolites in soil have potentially toxic effects on aquatic ecosystems. In this study, we explored the toxicity of haloxyfop-P-methyl on Chiromantes dehaani. The results of the 21-day toxicity test showed that haloxyfop-P-methyl decreased the weight gain (WG), specific growth rate (SGR) and hepatosomatic index (HSI). In glucose metabolism, haloxyfop-P-methyl reduced pyruvate, lactate, lactate dehydrogenase and succinate dehydrogenase, but enhanced glucose-6-phosphate dehydrogenase and hexokinase. Furthermore, expression of glucose metabolism-related genes was upregulated. We cloned the full-length CdG6PDH gene, which contains a 1587 bp ORF that encoded a 528 amino acid polypeptide. In antioxidant system, haloxyfop-P-methyl increased glutathione, thioredoxin reductase and thioredoxin peroxidase activities and activated the Nrf2/ARE pathway through upregulation of ERK, JNK, PKC and Nrf2. In immunity, low concentrations haloxyfop-P-methyl, or short-term exposure, upregulated the expression of immune-related genes and enhanced immune-related enzymes activity, while high concentrations or long-term exposure inhibited immune function. In summary, haloxyfop-P-methyl inhibited the growth performance, disrupted glucose metabolism, activated the antioxidant system, and led to immunotoxicity. The results deepen our understanding of the toxicity mechanism of haloxyfop-P-methyl and provide basic biological data for the comprehensive assessment of the risk of haloxyfop-P-methyl to the environment and humans.

Auricularia auricula-judae (Bull.) polysaccharides improve obesity in mice by regulating gut microbiota and TLR4/JNK signaling pathway

Obesity has emerged as a crucial factor impacting people's lives, and gut microbiota disorders contribute to its development and progression. Auricularia auricula-judae (Bull.) polysaccharides (AAPs), a traditional functional food in Asia, exhibit potential anti-obesity effects. However, the specific mechanism still needs to be further confirmed. This study investigated the beneficial effects and specific mechanisms of AAPs on obesity. Firstly, AAPs showed significant improvements in overweight, insulin resistance, glucose and lipid metabolism disorders, and liver damage in obese mice. Additionally, AAPs ameliorated gut microbiota disorders, promoting the proliferation of beneficial bacteria like Lactobacillus and Roseburia, resulting in increased levels of SCFAs, folate, and cobalamin. Simultaneously, AAPs inhibited the growth of harmful bacteria, thereby protecting intestinal barrier function, improving endotoxemia, and decreasing the levels of inflammatory factors such as TNF-α and IL-6. Furthermore, AAPs can inhibit the TLR4/JNK signaling pathway while promoting the activation of AKT and AMPK. Importantly, our study underscored the pivotal role of gut microbiota in the anti-obesity effects of AAPs, as evidenced by fecal microbiota transplantation experiments. In conclusion, our findings elucidated that AAPs improve obesity by regulating gut microbiota and TLR4/JNK signaling pathway, offering novel perspectives for further conclusion the anti-obesity potential of AAPs.

Glucose metabolism disorder: a potential accomplice of SARS-CoV-2.

Globally, 265,713,467 confirmed cases of SARS-CoV-2 (CoV-2), including 5,260,888 deaths, have been reported by the WHO. It is important to study the mechanism of this infectious disease. A variety of evidences show the potential association between CoV-2 and glucose metabolism. Notably, people with type 2 diabetes mellitus (T2DM) and other metabolic complications were prone to have a higher risk of developing a more severe infection course than people who were metabolically normal. The correlations between glucose metabolism and CoV-2 progression have been widely revealed. This review will discuss the association between glucose metabolism disorders and CoV-2 progression, showing the promoting effect of diabetes and other diseases related to glucose metabolism disorders on the progression of CoV-2. We will further conclude the effects of key proteins and pathways in glucose metabolism regulation on CoV-2 progression and potential interventions by targeting glucose metabolism disorders for CoV-2 treatment. Therefore, this review will provide systematic insight into the treatment of CoV-2 from the perspective of glucose metabolism.

Incidence and Factors Associated with Hyperglycemia in Patients with First Hospitalization for Major Depression Disorder: A Large Cross-Sectional Sample.

Major depressive disorder (MDD) is a mood disorder characterized by persistent spontaneous depression and has a high rate of disability and mortality. There is a complex relationship between MDD and disorders of glucose metabolism, and our study aimed to investigate the prevalence and risk factors for hyperglycemia in patients with MDD who were hospitalized for the first times. A total of 981 first-time inpatients with MDD were recruited, socio-demographic information, anthropometric data, and biochemical parameters were collected for each participant. The 17-item Hamilton Assessment Scale for Depression (HAMD-17), the 14-item Hamilton Anxiety Scale (HAMA-14), the Positive Syndrome Scale (PSS), and Clinical General Impressions Inventory-Severity of Illness (CGI-SI) scores were used to assess patients' clinical symptoms. The prevalence of hyperglycemia was 9.28% among patients with MDD who were hospitalized for the first time. Compared to the non-hyperglycemic subgroup, patients in the hyperglycemic subgroup were found to have more extensive and significant demographic and clinical characteristics, higher levels of metabolism-related parameters, and more severe psychological and psycho-pathological symptoms. Age, thyroid stimulating hormone (TSH), triglycerides (TG) were risk factors for hyperglycemia in MDD patients, while course of disease was a protective factor. The study findings suggest that the prevalence of hyperglycemia is not high in patients with MDD who are hospitalized for the first time. The risk variables for predicting hyperglycemia include age, TSH and TG. The above three factors and course of disease have good combined diagnostic ability for hyperglycemia.

Lipid metabolism-related gene signatures for predicting the prognosis of lung adenocarcinoma.

Lung cancer is one of the most common epithelial malignancies worldwide, accounting for the highest number of new cases and deaths. Metabolism is the sum of chemical reactions that produce energy to keep an organism alive. Several studies have shown that glucose and lipid metabolic disorders are common phenomena related to cancer cell genesis and progression. We screened the differentially expressed genes (DEGs) of lung adenocarcinoma (LUAD) samples of The Cancer Genome Atlas (TCGA) database, the Gene Set Enrichment Analysis (GSEA), and Gene Card database metabolism-related data, the metabolism-related DEGs of LUAD, as well as the univariate Cox regression analysis genes, for identifying significant outcome-related genes. The least absolute shrinkage and gene selection operator (LASSO) analysis was performed to establish the best risk model. Our study aimed to establish a lipid metabolism-related model for predicting LUAD prognosis. Furthermore, our model's prognosis prediction power was evaluated by survival analysis. This study finally identified 11 DEGs related to lipid metabolism that were significantly associated with the prognosis of lung adenocarcinoma. It provided a new idea for the treatment of high-risk lung adenocarcinoma patients. The constructed clinical prognosis model of lung adenocarcinoma related to lipid metabolism provides a new idea for clinical treatment of lung adenocarcinoma.

A metabolomics-based analysis of the metabolic pathways associated with the regulation of branched-chain amino acids in rats fed a high-fructose diet.

Previous studies, have shown that elevated levels of circulating BCAAs are associated with the development of insulin resistance and its complications, including obesity, type 2 diabetes, cardiovascular disease, and some cancers. However, animal models that can mimic the metabolic state of chronically elevated BCAAs in humans are rare. Therefore, the aim of this study was to establish the above animal model and analyze the metabolic changes associated with high BCAA levels. Sixteen 8-week-old SD rats were randomly divided into two groups and given either a high fructose diet or a normal diet. BCAA levels as well as blood glucose and lipid levels were measured at different time points of feeding. The mRNA expression levels of two key enzymes of BCAA catabolism, ACAD (acyl-CoA dehydrogenase) and BCKDH (branched-chain α-keto acid dehydrogenase), were measured by qPCR, and the protein expression levels of these two enzymes were analyzed by immunohistochemistry. Finally, the metabolite expression differences between the two groups were analyzed by Q300 metabolomics technology. Our study confirms that defects in the catabolic pathways of BCAAs lead to increased levels of circulating BCAAs, resulting in disorders of glucose and lipid metabolism characterized by insulin resistance by affecting metabolic pathways associated with amino acids and bile acids.

Association of Gestational Diabetes Mellitus Complicated With Short Sleep Duration and Child Neurodevelopmental Delay.

Gestational diabetes mellitus (GDM) is a risk factor for child neurodevelopmental delay. Maternal short sleep duration (SSD) may aggravate glucose metabolism disorder in women with GDM. However, it is unclear whether maternal SSD will further affect the neurodevelopmental outcomes of children. To identify the association of GDM complicated with SSD and child neurodevelopmental delay. This prospective study included 7069 mother-child pairs. Between 24 and 28 weeks of gestation, GDM was based on the 75-g oral-glucose-tolerance test. Self-reported sleep duration was collected via the Pittsburgh Sleep Quality Index questionnaire in the second (24-28 weeks) and third (32-36 weeks) trimesters. Outcomes of neurodevelopmental delay in 6 to 36 months postpartum were evaluated using Denver Developmental Screening Test-II and Gesell Development Diagnosis Scale. Compared with the unexposed group, women with "GDM + SSD" have the greatest risks of child neurodevelopmental delay (hazard ratio with 95% CI: 1.58 [1.03-2.44]). "GDM + SSD" was associated with the greatest risks of maternal-fetal glucose metabolic disorder. An interquartile ratio (0.58 mmol/L) increase in cord blood C-peptide was associated with the risk of child neurodevelopmental delay (hazard ratio with 95% CI: 1.28 [1.12-1.48]). The stronger linear association of maternal glucose metabolism profiles and C-peptide in women with "GDM + SSD" was also demonstrated. The proportion of association between "GDM + SSD" and child neurodevelopmental delay mediated by C-peptide was 14.4%. GDM complicated with SSD was associated with increased risk for child neurodevelopmental delay by enhancing the intergenerational association of maternal-fetal glucose metabolism disorder.

Ketogenic diet: a potential adjunctive treatment for substance use disorders.

Substance use disorders (SUD) can lead to serious health problems, and there is a great interest in developing new treatment methods to alleviate the impact of substance abuse. In recent years, the ketogenic diet (KD) has shown therapeutic benefits as a dietary therapy in a variety of neurological disorders. Recent studies suggest that KD can compensate for the glucose metabolism disorders caused by alcohol use disorder by increasing ketone metabolism, thereby reducing withdrawal symptoms and indicating the therapeutic potential of KD in SUD. Additionally, SUD often accompanies increased sugar intake, involving neural circuits and altered neuroplasticity similar to substance addiction, which may induce cross-sensitization and increased use of other abused substances. Reducing carbohydrate intake through KD may have a positive effect on this. Finally, SUD is often associated with mitochondrial damage, oxidative stress, inflammation, glia dysfunction, and gut microbial disorders, while KD may potentially reverse these abnormalities and serve a therapeutic role. Although there is much indirect evidence that KD has a positive effect on SUD, the small number of relevant studies and the fact that KD leads to side effects such as metabolic abnormalities, increased risk of malnutrition and gastrointestinal symptoms have led to the limitation of KD in the treatment of SUD. Here, we described the organismal disorders caused by SUD and the possible positive effects of KD, aiming to provide potential therapeutic directions for SUD.

Nuciferine ameliorates high‐fat diet‐induced disorders of glucose and lipid metabolism in obese mice based on the gut–liver axis

AbstractHigh‐fat diets (HFDs) can trigger lipid accumulation, insulin resistance, and inflammatory responses in the body, causing glucose and lipid metabolism dysfunction. This study aimed to explore the role of nuciferine on HFD‐induced disorders of glucose and lipid metabolism in obesity mice models, and further to identify the possible underlying mechanisms. In our experiments, nuciferine effectively ameliorated HFD‐induced insulin resistance by IRS/PI3K/AKT pathway, and alleviated HFD‐induced lipid accumulation via AMPK‐mediated regulation of FAS and ATGL expression. Nuciferine also suppressed HFD‐induced intestinal pathological damage, as evidenced by the improvement of intestinal barrier integrity and the increasing in expressions of tight junction proteins of claudin, ZO‐1, and occludin. In addition, 16S rRNA gene sequencing of the fecal microbiota suggested that nuciferine changed the diversity and the composition of gut microbiota in HFD‐fed mice. Nuciferine decreased the ratio of Firmicutes/Bacteroidetes, the relative abundance of LPS‐producing genus Desulfovibrio and the bacteria which involved in lipid metabolism. In summary, nuciferine ameliorated the disorders of glucose and lipid metabolism in obese mice via balancing the gut–liver axis.

Dendrobine rescues cognitive dysfunction in diabetic encephalopathy by inhibiting ferroptosis via activating Nrf2/GPX4 axis

BackgroundFerroptosis playsa crucial role in the development of dementia and dendrobine (Den)possesseshypoglycemic and neuroprotective effects. However, the character of ferroptosis in diabetic encephalopathy (DE) and Den's therapeutic effect remains unclear. PurposeThis study aimed to verify the effects of Den on ferroptosis in treating DE and underlying mechanisms. Study designDen's therapeutic effect was assessed in db/db mice and advanced glycation end products (AGEs)-induced HT22 cells. MethodsAfter oral administration with Den orMetformin for 8-week, behavioral tests were used to assess cognitive capacity. Then, biochemical analysis was preformed to detect glucose and lipid metabolism levels; histological analysis and transmission electron microscope were applied to evaluate pathological injuries. Meanwhile, EdU staining and flow cytometry were applied to test cell apoptosis. Furthermore, mitochondrial dynamics, iron transport, and Nrf2/GPX4 axis related proteins were detected by western blot or immunofluorescence. ResultsOur results demonstrated that Den remarkably alleviated glucose and lipid metabolism disorders, as well as ameliorated mnemonic deficits of db/db mice. Meanwhile, Den could protect AGEs-induced HT22 cells from death and apoptosis. In addition, we noted that Den inhibited lipid peroxidation by restoring mitochondrial function and reducing reactive oxygen species production. Furthermore, ferroptosis was proven to exist in db/db mice brain and Den could inhibit it via activating Nrf2/GPX4 axis. ConclusionThese findings indicated that Den could rescue cognitive dysfunction in DE by inhibiting ferroptosis via activating Nrf2/GPX4 axis.

A Rational Combination of Cyclocarya paliurus Triterpene Acid Complex (TAC) and Se-Methylselenocysteine (MSC) Improves Glucose and Lipid Metabolism via the PI3K/Akt/GSK3β Pathway.

Cyclocarya paliurus (CP) contains triterpene acids that can improve glucose and lipid metabolism disorders. However, controlling the composition and content of these active ingredients in CP extracts is challenging. The main active components in CP triterpene acids, including ursolic acid (UA), oleanolic acid (OA), and betulinic acid (BA), exhibit antihyperglycemic and antihypertensive effects. The response surface methodology was utilized to design and optimize the ratio of UA, OA, and BA based on the inhibition rate of pancrelipase and α-amylase. The proportional mixture of UA, OA, and BA resulted in the formation of a complex known as Cyclocarya paliurus triterpenoid acid (TAC). Se-methylselenocysteine (MSC), a compound with various physiological functions such as antioxidant properties and tumor inhibition, has been used in combination with TAC to form the TAC/MSC complex. Our data demonstrate that TAC/MSC improved palmitic acid (PA)-induced insulin resistance in HepG2 cells through activating the phosphoinositide 3-kinase (PI3K) /protein kinase B (AKT)/glycogen synthase kinase 3 beta (GSK3β) pathway. Moreover, TAC/MSC effectively improved hyperglycemia, glucose intolerance, insulin resistance, and lipid metabolism disorder in mice with type 2 diabetes mellitus (T2DM), attenuated hepatic steatosis, and reduced oxidative stress to alleviate T2DM characteristics.