OBJECTIVES

In Asia, younger individuals (below age 45) are diagnosed to have type 2 diabetes with increased rates of obesity defined by lower BMI yet with greater visceral adiposity (waist circumference and waisthip ratios). The prevalence data on type 1 diabetes is not well established, considered to be low, but is seen to be increasing as well. This changing phenotype therefore, presents a clinical dilemma in terms of correctly classifying diabetes and deciding on the consequent appropriate treatment. Distinguishing type 1 from type 2 diabetes has become more difficult with type 2 diabetes dramatically increasing in young adults and children. This study aims to define the characteristics of diabetes among young adults in the Philippines to provide a basis for appropriate management amidst changes in diabetes phenotypes seen globally.

METHODS

In this cross-sectional analytic study, we characterized the demographic, metabolic, and autoimmune features of diabetes among young adult Filipinos aged 18 to 45 years old consulting at a tertiary referral center in Manila, Philippines. Baseline serum A1c, FBS, 75-g oral glucose tolerance test, insulin, serum C-peptide, insulin autoantibodies, leptin, adiponectin, lipid profile, and thyroid function tests were obtained from the participants and analyzed. The homeostasis model assessment (HOMA) was used to estimate the insulin sensitivity.

RESULTS

A total of 348 patients with diabetes were included, with females comprising two-thirds of the participants. The mean age at diagnosis of diabetes was 35.9±7.22 years. The mean BMI was 28.12 kg/m2, with median waist to hip ratio (WHR) of 0·93. Metabolic syndrome was found in 60% of participants and 67.82% were obese by body mass index. The mean A1c was 9.07±2.52%. Good glucose control (A1c less than 7.0%) was seen in 23% of participants  while nearly half (48%) had HbA1c which was >9.0%. The median levels of fasting insulin and C-peptide were 12.62 (range 1.33–90.42) mIU/L and 0.78 ng/mL (range 0–16.2), respectively. 

Included participants were diagnosed with diabetes within a year and as such, majority did not have any micro- or macrovascular complications. The most common diabetes complication was sensory neuropathy detected by monofilament testing, which was found in 28% of participants, followed by non-proliferative diabetic retinopathy in 13%. A history of previous diabetic ketoacidosis was found in 10 patients (2.87%). Glutamic acid decarboxylase (GAD) and insulin auto-antibodies were found in 3.2% and 19.3% of participants, respectively. Approximately half (51.73%) of the participants were insulin resistant by HOMA-IR.

CONCLUSION

In contrast with Caucasians and other Asians, diabetes among young Filipino adults is associated with lower BMI but with a similarly high visceral adiposity as shown by an elevated WHR. Metabolic syndrome with insulin resistance as defined by a variety of indices is predominant. Type 1 diabetes with autoantibodies occur in only a small fraction of this population. Data derived from this work can provide a framework for cluster analysis towards personalized management specific to this population.

Human ; Acids ; Adiponectin ; Adiposity ; Adult ; Aged ; Antibodies ; Asia ; Asian ; Asian Continental Ancestry Group ; Autoantibodies ; Body Mass Index ; C-peptide ; Carboxy-lyases ; Child ; Cluster Analysis ; Demography ; Diabetes Complications ; Diabetes Mellitus ; Diabetes Mellitus, Type 1 ; Diabetes Mellitus, Type 2 ; Diabetic Ketoacidosis ; Diabetic Retinopathy ; Diagnosis ; Fasting ; Female ; Glucose ; Glucose Tolerance Test ; Glutamate Decarboxylase ; Glutamic Acid ; Insulin ; Insulin Resistance ; Ketosis ; Leptin ; Lipids ; Metabolic Syndrome ; Obesity ; Patients ; Peptides ; Phenotype ; Philippines ; Population ; Prevalence ; Serum ; Therapeutics ; Thyroid Gland ; Thyroid Function Tests ; Young Adult

Introduction: Prediabetes or intermediate hyperglycemia (IH) represents a critical phase in the trajectory toward type 2 diabetes mellitus (T2DM). Recent evidence from the International Diabetes Federation (IDF) suggests that 1-hour OGTT (1HOGTT) ≥8.6 mmol/L is a more sensitive biomarker for early beta-cell dysfunction, with enhanced detection of IH and future T2DM risk. Conventional screening using hemoglobin A1c (HbA1c) or 2-Hour OGTT (2HOGTT) may delay identification of prediabetes, narrowing the window for early intervention. This study evaluates 1HOGTT as a screening tool for prediabetes among Malaysians. Methodology: This cross-sectional study enrolled adults without prior T2DM or prediabetes. Participants underwent 1HOGTT, 2HOGTT, and HbA1c, classified as per the Malaysian Clinical Practice Guideline for T2DM (6th Edition) and IDF 2024 criteria. Agreement between tests was assessed using McNemar’s test and Cohen’s kappa. Diagnostic accuracy was evaluated via receiver operating characteristic (ROC) curve analysis. Cost-effectiveness was determined using reagent cost only. Results: The majority of the 310 participants were female (71.6%), Malay (87.1%), with average age of 40. The 1HOGTT identified prediabetes in 21.6% (n = 67) compared to 17.1% (n = 53) by HbA1c and 2.6% (n = 8) by 2HOGTT. McNemar’s test confirmed statistically significant discordance between 1HOGTT and 2HOGTT (chi-square = 53.397, p <0.001): 61 participants were prediabetic by 1HOGTT but normal by 2HOGTT, versus only 2 in the reverse direction. No significant discordance was found between 1HOGTT and HbA1c (chi-square = 2.817, p = 0.093). 1HOGTT demonstrated excellent discriminatory ability against 2HOGTT (AUC = 0.908; 95% CI: 0.837–0.978), significantly outperforming HbA1c (AUC = 0.664; CI: 0.462– 0.867; DeLong p = 0.012). In a population-level cost analysis, 1HOGTT achieved lowest cost per prediabetes case detected (RM 5.79) – approximately 8.3 times and 8.1 times more cost-effective than 2HOGTT (RM 48.08) and HbA1c (RM 46.78) respectively. Conclusion 1HOGTT identifies a significant proportion of individuals with prediabetes missed by 2HOGTT and HbA1c. Incorporating 1HOGTT enhances the detection of prediabetes, is cost-effective, and enables timely preventive measures in our population with high diabetes burden.
Glucose Tolerance Test ; Glycated Hemoglobin ; Prediabetic State

Introduction: Sodium-glucose-linked-transporter inhibitors (SGLT2-i) have demonstrated cardiovascular and renal benefits in type 2 diabetes mellitus (T2DM), but patients aged ≥75 years remain underrepresented in major trials, creating uncertainty regarding their risk–benefit profile. Real-world data show mixed safety signals. In Malaysia, local evidence is limited despite a growing elderly diabetic population. This study evaluates the glycemic efficacy and safety of SGLT2-i in advanced elderly patients in a real-world public hospital setting. Methodology: We conducted a retrospective observational cohort study of patients aged ≥75 years with T2DM initiated on SGLT2-i in Hospital Putrajaya (2020–2024). Electronic records were reviewed for demographics, comorbidities, medications, and biochemical parameters. Outcomes at 6–12 months assessed glycemic control and safety. Adverse events and discontinuation rates were recorded. Patients with incomplete data, type 1 diabetes, active malignancy, or severe renal impairment were excluded. Results: A total of 104 patients (mean age 78.2 years; 54% female) were included with a high proportion (76.9%) classified as at high cardiovascular risk due to established macrovascular disease (57.7%) or nephropathy (53.8%). Indications for SGLT2-i initiation were glycemic control alone (69.2%) and together with cardiorenal protection (58.7%). Glycemic control remained stable (hemoglobin A1c: 7.66–7.45%; p = 0.076), with preserved renal function (estimated glomerular filtration rate: 58.65–58.11 mL/min/1.73 m²; p = 0.575). Overall safety was favorable, with 90.4% experiencing no adverse events. Minor adverse events included urinary tract infections (2.9%) and polyuria (1.9%). ASCVD-related hospitalizations occurred in 4.8% of patients, with a low discontinuation rate (7.7%). A statistically significant weight reduction was observed (baseline 66.67 kg, −1.01 kg; p = 0.005) but was not clinically significant. Proteinuria improvement was noted in 15.7% of patients. Conclusion SGLT2-i are safe and well-tolerated in elderly T2DM patients (≥75 years), with stable glycemic control, preserved renal function, and minimal adverse events, supporting their use in very elderly Asian populations.
Aged ; Diabetes Mellitus, Type 2 ; Sodium-Glucose Transporter 2 Inhibitors

Introduction: Malaysia has one of the highest diabetes prevalence rates in Asia (1 in 5), with >50% fail to achieve optimal glycemic control. Continuous glucose monitoring (CGM) provides detailed insights beyond hemoglobin A1c (HbA1c), capturing daily glucose fluctuations and variability. Realworld data describing CGM patterns and their clinical associations in Malaysian adults with type 2 diabetes mellitus (T2DM) are limited. Methodology: This cross-sectional study analyzed CGM data from 25 Malaysian adults with T2DM, standardized over 14 days. CGM metrics included time in range (TIR), time above range (TAR), time below range (TBR), mean glucose, and coefficient of variation (CV). Weekday–weekend comparisons were performed, and correlations with age, diabetes duration, HbA1c, body mass index (BMI), treatment regimen, and complications were assessed. Results: Participants had a mean age of 56.2 ± 13.2 years (52% male), mean HbA1c 9.4 ± 2.7%, diabetes duration 10.7 ± 9.0 years, and BMI 29.8 ± 9.4 kg/m². Mean TIR, TAR, TBR, mean glucose, and CV were similar between weekdays and weekends (p >0.34 for all). TIR >70% was achieved by 52% of participants on weekdays and 48% on weekends, with no statistically significant difference (p = 0.75). Longer diabetes duration correlated with lower TIR (r = −0.62, p <0.001), higher mean glucose (r = 0.58, p = 0.002), and greater variability (r = 0.54, p = 0.004). Older age was associated with lower TIR (r = −0.48, p = 0.014) and higher mean glucose (r = 0.44, p = 0.025). Higher HbA1c correlated with lower TIR (r = −0.36, p = 0.04), higher TAR (r = 0.35, p = 0.05), greater variability (r = 0.51, p = 0.006), and increased target organ damage (ρ = 0.55, p = 0.004). BMI was not associated with TIR (r = −0.18, p = 0.38). Participants with ≥2 complications had lower TIR (55.8 ± 28.4% vs 76.7 ± 19.2%, p = 0.073), while insulin the Conclusion In Malaysian adults with T2DM, CGM metrics were similar between weekdays and weekends, indicating lifestyle differences had minimal impact on glycemic control. Longer diabetes duration, older age, higher HbA1c, multiple complications, and insulin therapy identified patients at highest risk for poor glycemic control, greater variability, and hypoglycemia. These findings support the use of CGM for risk stratification, individualized monitoring, and therapy optimization to reduce complications and hypoglycemia risk.
Adult ; Blood Glucose ; Blood Glucose Self-Monitoring ; Continuous Glucose Monitoring ; Diabetes Mellitus, Type 2

Introduction: Sodium-glucose cotransporter-2 (SGLT2) inhibitors are cornerstone therapies for heart failure and diabetes, offering proven cardiorenal benefits. However, expanded use necessitates vigilance regarding adverse effects, particularly genitourinary infections. While mild cystitis is common, serious upper urinary tract infections remain rare and potentially life-threatening. We describe a case of renal abscess presenting as recurrent urinary tract infections (UTI) following SGLT2 inhibitor initiation, emphasizing the need for clinical vigilance. Case: A 69-year-old male with a significant cardiovascular history, including heart failure with reduced ejection fraction (HFrEF), hypertrophic cardiomyopathy with an implantable cardioverter-defibrillator for non-sustained ventricular tachycardia, diabetes mellitus, hypertension, and hyperlipidemia, presented with a 1-week history of right flank pain, dysuria, urinary frequency, and fever. Initial labs confirmed infection: leukocytosis (22.6 × 10³/ µL), markedly elevated CRP (200 mg/L), and bacteriuria. He was diagnosed with a UTI and started on IV Cefuroxime. This marked his third UTI admission in 5 months, following discharge just 3 weeks prior for septic shock secondary to UTI, establishing a relapsing pattern. Subsequent urine and blood cultures were unremarkable. Medication review revealed Dapagliflozin had been initiated for HFrEF 8 months ago. Following clinical improvement from each prior UTI episode, Dapagliflozin was consistently restarted. Despite an initial antibiotic response, symptoms recurred after discharge each time. The recurrent nature of his infections prompted a renal ultrasound revealing a large (5.3 × 7.5 × 7.4 cm), non-drainable, heterogeneously hypoechoic collection at the left kidney’s mid-lower pole, diagnostic of an early renal abscess. Conclusion This report highlights renal abscess as a rare and severe complication of SGLT2 inhibitor therapy. It serves as a critical reminder that recurrent or relapsing UTIs in patients on these agents should prompt immediate investigation with renal imaging to rule out deep-seated pathology rather than simple cystitis. While these drugs offer proven cardiorenal benefits, their role in promoting urological infections necessitates a cautious approach.
Abscess ; Sodium-Glucose Transporter 2 Inhibitors

BACKGROUND

Diabetes mellitus (DM) remains a major global health burden, with increasing prevalence in developing countries such as the Philippines. Accuracy of glucose measurement is vital for diagnosis and management; however, preanalytical variables, particularly glycolysis from varying collection tubes, temperature and time interval can significantly affect test results. Despite guideline recommendations favoring plasma, serum is still commonly used in local clinical practice.

OBJECTIVE

This study evaluated the effectiveness of different commercially available blood collection tubes in preserving glucose stability by minimizing pre-analytical glycolysis.

METHODOLOGY

A cross-sectional observational and quasi-experimental study was conducted among 40 healthy adult participants (18–59 years) from a tertiary institution in Quezon City, Philippines. A total of 160 samples were collected using four tube types (one plasma and three serum tubes). Samples were analyzed at varying time intervals (0–180 minutes) and storage conditions (room temperature and 4°C). Glucose levels were measured using the glucose oxidase method. Statistical analysis included Shapiro–Wilk, Kruskal–Wallis H-test, Welch’s t-test, and Dwass–Steel–Critchlow–Fligner post hoc comparisons at a 1% significance level.

RESULTS

Glucose concentrations differed significantly across tube types (pCONCLUSION

Blood collection tube type and delayed processing significantly influence glucose measurements. While acceptable within analytical limits, systematic biases may affect clinical interpretation. Standardization of blood collection practices and stricter pre-analytical protocols are essential to improve diagnostic accuracy for diabetes in the Philippines.

Medical Laboratory Science ; Diabetes Mellitus ; Blood Glucose ; Fasting

Introduction: ISPAD guidelines recommend continuous glucose monitoring (CGM) as the standard of care for paediatric type 1 diabetes (T1DM). However, a “real-world” adoption gap persists, particularly in resource-limited settings. The Introductions of the study were to evaluate CGM adoption prevalence, identify documented barriers, and compare glycemic outcomes between active and non-active users. Methodology: This retrospective review analyzed electronic medical records (EMR) of 125 paediatric T1DM patients at Hospital Putrajaya (2025). Data included CGM status, insulin delivery method, and documented barriers. Independent T-tests compared mean hemoglobin A1c (HbA1c) between groups, and multivariable logistic regression identified independent predictors of adoption. Results: Cohort mean age was 11.8 ± 3.8 years. Active CGM users were 32.8% (n = 41), of whom 29.3% (n = 12) utilized predominantly automated insulin delivery (AID) systems. The remaining 67.2% (n = 84) were classified as non-active users, comprising both never-users and ex-users (discontinued use). Active users achieved significantly lower mean HbA1c than non-active users (8.73% vs 9.86%; p <0.001), with no significant difference in rates of DKA (p = 0.564) or severe hypoglycemia (p = 0.250). Among never-users, 42.9% lacked documented technology counselling (p = 0.001). Multivariable analysis identified funding source as the sole independent predictor of CGM adoption (adjusted OR = 7.76, p <0.001). While the primary documented barrier was financial (31.0%), a lack of documented barriers was noted in 61.9% of non-active users. Conclusion A substantial technology gap exists, primarily driven by financial access rather than clinical demographics. The difference of 1.13% in HbA1c between groups underscores the need to address financial setbacks to improve technology access in Malaysia and prevent diabetes complications.
Child ; Blood Glucose ; Blood Glucose Self-Monitoring ; Continuous Glucose Monitoring ; Diabetes Mellitus, Type 1

Introduction: Glycolysis continues after blood collection and may reduce glucose concentrations in vitro, potentially compromising diagnostic accuracy. The effectiveness of glycolysisinhibiting additives differs among blood collection tubes. Citrate rapidly inhibits glycolysis through immediate acidification, whereas fluoride acts more slowly by inhibiting enolase at a later stage of the glycolytic pathway. This study aimed to compare short-term glucose stability in four commonly used blood collection tubes under routine laboratory conditions. Methodology: Venous blood samples were collected from 100 volunteers into Rapid Serum Tubes (RST), Barricor tubes, Fluoride tubes, and Citrate tubes. Glucose concentrations were measured at 30 and 60 minutes after collection using the hexokinase method. A repeated-measures ANOVA was performed to evaluate the effects of Time, Tube Type, and the Time × Tube interaction (α = 0.05), followed by Bonferroni-adjusted pairwise comparisons. Results: At 30 minutes, glucose concentrations were highest in the Fluoride tube (5.528 mmol/L), followed closely by the Citrate tube (5.505 mmol/L), while lower values were observed in RST (5.434 mmol/L) and Barricor tubes (5.430 mmol/L). By 60 minutes, glucose levels had declined in all tubes; however, the decrease was more pronounced in serum-based tubes. RST values fell to 5.277 mmol/L and Barricor to 5.300 mmol/L, whereas Fluoride and Citrate tubes remained relatively stable at 5.449 mmol/L and 5.489 mmol/L, respectively. Overall, glucose decreased significantly between 30 and 60 minutes (mean decrease = 0.096 mmol/L, p <0.001; partial η² = 0.705). Tube Type also had a significant effect on glucose concentrations (F(3,297) = 42.06, p <0.001; partial η² = 0.298). Conclusion Fluoride and Citrate tubes provided the most effective preservation of glucose concentrations over 60 minutes, showing minimal glycolytic decline. In contrast, RST and Barricor tubes demonstrated significantly greater glucose loss, highlighting the importance of rapid processing when serum-based tubes are used.
Glucose

OBJECTIVE: To elucidate the clinical and genetic characteristics of familial cases with Glucose transporter type 1 deficiency syndrome (Glut1DS). METHODS: A survey of family history was conducted on children (proband) with Glut1DS who had visited Peking University First Hospital between November 2008 and April 2024 by focusing on the clinical manifestations of family members. Peripheral venous blood (2 mL) was collected from the pediatric patients and their parents. Genomic DNA was extracted and sequenced subsequently. Sanger sequencing was performed to validate the identified variant sites of the SLC2A1 gene in the probands and their family members. The pathogenicity of suspected variants was analyzed according to the 2015 American College of Medical Genetics and Genomics (ACMG) Standards and Guidelines for the Interpretation of Sequence Variants. The clinical features, auxiliary examinations, and mutational characteristics of family members with SLC2A1 variants were analyzed. This study has been approved by the Clinical Research Ethics Committee of Peking University First Hospital (Ethics No. 2021 Research 332). RESULTS: Among 87 cases with Glut1DS, 10 families with autosomal dominate inherited cases were identified, accounting for 11.0% of the cases. Of the 11 children, 8 were boys and 3 were girls. The onset of the disease had ranged from 3 months to 120 months (median 6 months), with 4 cases of early-onset classic type, 2 cases of late-onset classic type, and 5 cases of non-classic type. Six children had seizures, and 7 exhibited movement disorders. Seven children underwent developmental assessment, of which 3 had mild developmental delay, 2 were borderline, and 2 were normal. Nine children underwent lumbar puncture. The cerebrospinal fluid glucose levels ranged from 1.45 to 2.25 mmol/L (median 1.86 mmol/L), and the cerebrospinal fluid to blood glucose ratios ranged from 0.29 to 0.44 (median 0.35). Among the 8 fathers with SLC2A1 gene variants, 4 were asymptomatic, 2 developed paroxysmal exercise-induced movement disorders (PED) in childhood and adulthood, respectively. 1 had poor memory since childhood, 1 developed migraines during adolescence, and his sister was an asymptomatic carrier. The father with childhood-onset PED had a cerebrospinal fluid test with CSF glucose of 1.85 mmol/L. Of the 3 mothers with SLC2A1 gene mutations, 1 was an asymptomatic carrier; 2 developed PED in childhood and after the age of 20, respectively. The mother who developed PED in childhood also had psychomotor developmental delay. Genetic testing results revealed that among 10 families, 8 carried missense variants, 1 carried a nonsense variant, and 1 carried a small fragment insertion leading to a frameshift variant. Among the 11 cases, SLC2A1 gene variants in 8 children were inherited from their fathers, while in 3 cases, the variants were inherited from their mothers. The pathogenicity of the genetic variants was evaluated according to the Standards and Guidelines for the Interpretation of Sequence Variants published by the ACMG. Among the 8 variants identified in the 10 families, 4 were classified as pathogenic variants, 1 as likely pathogenic, and 3 as variants of uncertain significance (VUS). Four variant sites, including c.204_205insTCTC (p.V69fs), c.412G>C (p.G138R), c.431T>G (p.V144G), and c.875A>G (p.Y292C), were not previously reported in the literature. Among these, the latter three were categorized as VUS. CONCLUSION Familial Glut1DS account for 11.0% of the cases in China, with the majority of SLC2A1 gene variants inherited from the fathers, predominantly missense mutations, and with an autosomal dominant inheritance pattern. Probands tend to have earlier onset and more severe symptoms than their parents, who often present with mild or no symptoms.
Humans ; Male ; Female ; Glucose Transporter Type 1/deficiency* ; Monosaccharide Transport Proteins/deficiency* ; Child ; Child, Preschool ; Carbohydrate Metabolism, Inborn Errors/genetics* ; Mutation ; Infant ; Pedigree ; Adolescent ; Adult

OBJECTIVE: To explore the effects and mechanisms of the C-X-C motif chemokine ligand 12/C-X-C motif chemokine receptor 4 (CXCL12/CXCR4) signaling axis on apoptosis and autophagy in SH-SY5Y neuronal cells subjected to oxygen-glucose deprivation/reperfusion (OGD/R) model in vitro. METHODS: SH-SY5Y cells were divided into the following groups: OGD/R group and non-OGD/R group, with the OGD/R group subjected to OGD/R modeling and the non-OGD/R group receiving no treatment. Cells were also divided into CXCL12⁺ and CXCL12^- groups; the CXCL12⁺ group received 0.1 mg/L exogenous recombinant CXCL12 (rhCXCL12) at reoxygenation, while the CXCL12^- group did not. Another set of cells was divided into CXCL12+AMD3100 and CXCL12 groups; the CXCL12+AMD3100 group was pretreated with 2.5 mg/L AMD3100, a CXCR4 inhibitor, for 2 hours before OGD/R and received both 2.5 mg/L AMD3100 and 0.1 mg/L rhCXCL12 at reoxygenation, whereas the CXCL12 group received rhCXCL12 only. Additionally, cells were divided into small interfering RNA CXCR4 (siCXCR4) and small interfering RNA negative control (siNC) groups; the siCXCR4 group underwent CXCR4 knockdown before OGD/R modeling and received 0.1 mg/L rhCXCL12 at reoxygenation, while the siNC group, transfected with a negative control, received the same treatment. Protein expression of autophagy-related 16 (ATG16), microtubule-associated protein 1 light chain 3 (LC3), aquaporin-3 (AQP3), and CXCR4 was detected by Western blotting. Apoptosis rate and CXCR4 expression were measured by flow cytometry. RESULTS: Compared with the non-OGD/R group, the OGD/R group showed a significantly increased apoptosis rate and markedly decreased protein expression levels of ATG16, LC3, AQP3, and CXCR4 (all P < 0.05). CXCR4 fluorescent expression was also significantly reduced, suggesting that OGD/R simultaneously affects neuronal apoptosis and autophagy while inhibiting CXCR4 and AQP3 expression in SH-SY5Y cells. Compared with the CXCL12^- group, the CXCL12⁺ group exhibited no significant change in apoptosis rate but demonstrated significantly increased protein expression of ATG16, LC3, and AQP3 (ATG16/GAPDH: 1.21±0.10 vs. 1.00±0.00; LC3/β-actin: 1.22±0.10 vs. 1.00±0.00; AQP3/β-actin: 1.26±0.04 vs. 1.00±0.00; all P < 0.05). CXCR4 expression was also significantly enhanced (fluorescence intensity: 1.19±0.05 vs. 1.00±0.00, P < 0.05), indicating that CXCL12 may promote autophagy in OGD/R-injured SH-SY5Y cells via the CXCR4/AQP3 pathway. Compared with the CXCL12 group, the CXCL12+AMD3100 group showed no significant difference in apoptosis rate but significantly lower protein levels of ATG16 and LC3 (ATG16/GAPDH: 0.75±0.08 vs. 1.00±0.00; LC3/GAPDH: 0.86±0.07 vs. 1.00±0.00; both P < 0.05), suggesting that CXCL12 induces autophagy in OGD/R SH-SY5Y cells through CXCR4. Compared with the siNC group, the siCXCR4 group showed no significant change in apoptosis rate but significantly reduced protein expression of ATG16, LC3, AQP3, and CXCR4 (ATG16/GAPDH: 0.76±0.06 vs. 1.00±0.00; LC3/GAPDH: 0.79±0.11 vs. 1.00±0.00; AQP3/GAPDH: 0.81±0.05 vs. 1.00±0.00; CXCR4/GAPDH: 0.86±0.04 vs. 1.00±0.00; all P < 0.05), indicating that CXCR4 knockdown suppresses OGD/R-induced autophagy in SH-SY5Y cells likely via AQP3. CONCLUSIONS The CXCL12/CXCR4 signaling axis can regulate OGD/R-induced autophagy in SH-SY5Y cells through AQP3 without affecting apoptosis, indicating a role for this pathway in neuronal autophagy during cerebral ischemia/reperfusion injury.
Humans ; Receptors, CXCR4/metabolism* ; Chemokine CXCL12/metabolism* ; Autophagy ; Glucose/metabolism* ; Apoptosis ; Neurons/cytology* ; Oxygen/metabolism* ; Signal Transduction ; Cell Line, Tumor ; Cell Hypoxia ; Benzylamines ; Cyclams