Insulin Levels Research Articles

Enhanced ECCD36 signaling promotes skeletal muscle insulin resistance in female mice.

Consumption of a Western diet (WD) increases CD36 expression in vascular, hepatic, and skeletal muscle tissues promoting lipid metabolic disorders and insulin resistance. We further examined the role of endothelial cell-specific CD36 (ECCD36) signaling in contributing to skeletal muscle lipid metabolic disorders, insulin resistance, and their underlying molecular mechanisms. Female ECCD36 wild-type (ECCD36+/+) and knock-out (ECCD36-/-) mice, aged 6 wk, were provided with either a WD or a standard chow diet for a duration of 16 wk. ECCD36+/+ WD mice were characterized by elevated fasting plasma glucose and insulin levels, increased homeostatic model assessment for insulin resistance, and glucose intolerance that was blunted in ECCD36-/- mice. Improved insulin sensitivity in ECCD36-/- mice was characterized by increased phosphoinositide 3-kinases/protein kinase B signaling that further augmented glucose transporter type 4 expression and glucose uptake. Meanwhile, 16 wk of WD feeding also increased skeletal muscle free fatty acid (FFA) and lipid accumulation, without any observed changes in plasma FFA levels. These lipid metabolic disorders were blunted in ECCD36-/- mice. Moreover, ECCD36 also mediated in vitro palmitic acid-induced lipid accumulation in cultured ECs, subsequently leading to the release of FFAs into the culture media. Furthermore, consumption of a WD increased FFA oxidation, mitochondrial dysfunction, impaired mitochondrial respiratory, skeletal muscle fiber type transition, and fibrosis. These WD-induced abnormalities were blunted in ECCD36-/- mice. These findings demonstrate that endothelial-specific ECCD36 signaling participates in skeletal muscle FFA uptake, ectopic lipid accumulation, mitochondrial dysfunction, insulin resistance, and associated skeletal muscle dysfunction in diet-induced obesity.NEW & NOTEWORTHY ECCD36 exerts "extra endothelial cell" actions in skeletal muscle insulin resistance. ECCD36 is a major mediator of Western diet-induced lipid metabolic disorders and insulin resistance in skeletal muscle. Mitochondrial dysfunction is associated with diet-induced CD36 activation and related skeletal muscle insulin resistance.

Significance of measuring anthropometric and atherogenic indices in patients with polycystic ovary syndrome

BackgroundPolycystic ovary syndrome (PCOS) is a prevalent hormonal disorder affecting 5–15% of women of reproductive age, characterized by ovulatory dysfunction, hyperandrogenism, and polycystic ovarian morphology. PCOS is associated with metabolic disturbances such as dyslipidemia, insulin resistance (IR), and an increased risk of type 2 diabetes (T2DM) and cardiovascular disease.ObjectiveThe aim of this study is to apply new anthropometric indices [body adiposity index (BAI), visceral adiposity Index (VAI), lipid accumulation product (LAP), body roundness index (BRI), a body shape index (ABSI)] and new atherogenic indices [Castelli index-I, Castelli index-II, atherogenic risk of plasma (AIP), atherogenic coefficient (AC), lipoprotein combined index (LCI), triglycerides to high-density lipoprotein cholesterol (TG/HDL-C) ratio, metabolic score for insulin resistance (METS-IR), triglyceride glucose (TyG) index, triglyceride glucose-dody mass (TyG-BMI) index, triglyceride glucose-waist circumference (TyG-WC) index] metabolic score of insulin resistance to patients with PCOS.MethodsA retrospective analysis was conducted on 248 women diagnosed with PCOS based on the 2003 Rotterdam criteria. Anthropometric measurements, biochemical parameters, and atherogenic indices were collected from patient records. Statistical analyses were performed using Statistical Package for the Social Sciences software version 28.0.ResultsSignificant correlations were found between fasting glucose and various anthropometric indices, such as Body mass index (BMI), waist-height ratio (WHtR), and BAI, indicating a link between adiposity and glucose metabolism in PCOS. Atherogenic indices like Castelli’s risk indices, AIP, and AC showed positive correlations with glucose and insulin levels, reinforcing their role in assessing cardiovascular risk. Novel indices such as METS-IR and TyG demonstrated strong correlations with both glucose and insulin profiles, highlighting their potential as reliable markers for IR and cardiometabolic risk.ConclusionThe study underscores the importance of using a range of anthropometric and atherogenic indices for comprehensive metabolic assessment in women with PCOS. Indices like METS-IR and TyG offer valuable insights into insulin sensitivity and cardiovascular risk, potentially aiding in better management and prognosis of PCOS.

Insulin Resistance in Long COVID-19 Syndrome.

Background: The COVID-19 pandemic has caused severe health issues worldwide and contributed to huge financial losses. Key comorbidities linked to an increased risk of severe COVID-19 and higher mortality rates include cardio-metabolic disorders such as type 1 and type 2 diabetes mellitus (T1DM and T2DM), atherosclerotic cardiovascular disease, chronic kidney disease, hypertension, heart failure, and obesity. The persistence of symptoms even after the acute phase is over is termed long COVID-19 syndrome. This study aimed to evaluate the relationship between long COVID-19 syndrome and the development of insulin resistance in previously non-diabetic patients. Methods: A prospective observational study was performed on 143 non-diabetic patients who had tested positive for SARS-CoV-2 infection by a PCR test and were hospitalized in our hospital between January 2020 and December 2022. The clinical and para-clinical data at 0, 4, and 12 months of hospital admission for post-COVID-19 infection follow-up was collected and labeled as t0, t4, and t12. Blood glucose, insulin, and C-peptide levels were measured at the beginning and further at 2, 5, 10, and 30 min after the intravenous arginine stimulation test. Similarly, BMI was calculated, and hs-CRP and ESR levels were noted. The results obtained were statistically analyzed. Results: More than one-third (30.7%) of the included patients developed long COVID-19 syndrome. It was found that 75% of patients with long COVID-19 hospitalized in our clinic developed diabetes within a year of acute infection with COVID-19; therefore, it can be said that the presence of long COVID-19 is a major risk for an altered metabolic status, which can cause diabetes. When comparing the glycemia levels (106 mg/dL) with the BMI at t0, t4, and t12 time intervals, the p-values were found to be 0.214, 0.042, and 0.058, respectively. Almost 62% of the patients having BMI > 30 kg/m2 were found to have an increase in blood glucose levels at 1 year. Similarly, insulin resistance was noted during this interval. A negative correlation of 0.40 for hsCRP and 0.38 for ESR was noted when compared with acute infection with COVID-19. Conclusions: The association between long COVID-19 and insulin resistance highlights the varied and widespread impacts of SARS-CoV-2 infection. Addressing the complexities of long COVID-19 requires a holistic strategy that encompasses both respiratory and metabolic considerations, which is crucial for enhancing the well-being of those enduring this persistent condition.

A Study of Prevalence of Metabolic Syndrome in Premenopausal Women With Female Pattern Hair Loss: A Case-Control Study.

Background and objective Female pattern hair loss (FPHL), also known as androgenetic alopecia (AGA), is a condition where the hair follicles of genetically susceptible women gradually shrink and become thinner, leading to hair loss in a particular pattern. Metabolic syndrome (MS) is a collection of conditions that co-occur, increasing the risk of heart disease, stroke, and type 2 diabetes. This study aims to determine the prevalence of MS in premenopausal women in patients with FPHL. Methods and materials We conducted a case-control, hospital-based observational study at our institution for a period of two years, which included 62 patients, with 31 cases (patients with FPHL) and 31 controls (patients without FPHL). Results In some cases, the mean age was 29.81 years, while in controls, it was 28.84 years. The mean waist circumference (WC) in cases was 81.9+/- 11.75 cm, and in controls, it was 72.65+/- 8.86 cm, with a statistically significant p-value of 0.001. In some cases, the mean body mass index (BMI) was 26.28 +/- 4.09 kg/m2, and in controls, it was 24.52 +/- 2.78 kg/m2, with a statistically significant p-value of 0.013. Between cases and controls, there was no significant difference in the homeostatic model assessment of insulin resistance (HOMA-IR), fasting blood glucose (FBG), fasting triglyceride levels, fasting HDL, and fasting insulin levels. Conclusion The study found a significant association between WC and BMI in patients with FPHL in premenopausal women. This highlights the need for early screening and preventive measures for MS in women presenting with FPHL.

Exploring Factors Influencing Stroke Risk: Insights From a Predictive Analysis.

Introduction Stroke is a serious medical condition characterized by the sudden interruption of blood flow to the brain, resulting in the death of brain cells. It is a leading cause of long-term disability and mortality worldwide. Stroke has some associated risk factors, both modifiable and non-modifiable ones.As for non-modifiable risk factors, these are age, gender (men are more vulnerable), and family history of stroke.The controllable or adjustable risk factors include hypertension (high blood pressure), diabetes, smoking, high cholesterol levels, obesity, and insulin resistance. Methods In our study, we collected data from 229 patients which were originally collected for clinical purposes and were retrospectively analyzed. These data contain features such assex and age, the presence of ischemic heart disease (IHD) or stroke history, and different blood sugar readings. These measurements include fasting blood sugar (FBS), postprandial blood sugar (PPBS), HbA1c%, and insulin levels (fasting and postprandial).Furthermore, cholesterol was also tested, such as total cholesterol, triglycerides (TGL), high-density lipoprotein (HDL), low-density lipoprotein (LDL), and very low-density lipoprotein (VLDL). Surprisingly, stroke was observed in 24of the 205 patients. This contrast permits us to be concerned with the chance of the association between stroke and insulin levels. Given the imbalanced nature of our outcome variable (stroke occurrence), the primary analytical method will be logistic regression. Results In this cross-sectional study, we investigated the association between high insulin levels (both fasting and postprandial) and the occurrence of stroke within a dataset of 229 patients. Out of the 229 included cases, 102 individuals were female (44.5%) and 127 individuals were male (55.5%). Twenty-four cases have ischemic heart disease (10.5%). Among the analyzed cases, 24 individuals have a history of stroke. The average age of the sample is approximately 57 years ± 14.87. There was no significant difference between the males and females in most of the descriptive statistics. However, females experienced significantly higher levels of postprandial glucose level and significantly lower levels of postprandial insulin. According to our predictive model, we found that an increase in fasting insulin levels was linked to a lower risk of stroke occurrence. On the other hand, increasing insulin postprandial levels and age were associated with an increased risk of stroke. Conclusion Our study identified age, fasting insulin, and postprandial insulin as key factors influencing stroke risk. Higher fasting insulin levels were associated with reduced risk, while increased postprandial insulin and age were linked to higher risk. Blood glucose, cholesterol, and triglycerides had minor effects. Notably, higher total cholesterol and triglyceride levels were slightly associated with lower stroke occurrence. Further research with larger samples is needed for validation.

The KCa3.1 channel blocker TRAM-34 and minocycline prevent fructose-induced hypertension in rats.

High fructose consumption increases blood pressure through microglia-related neuroinflammation in rats. Since intermediate-conductance calcium-activated potassium channels (KCa3.1) potentiates microglial reactivity, we examined whether the pretreatment with the KCa3.1 channel blocker TRAM-34 or minocycline prevents hypertension development in fructose-fed rats. The study involved male Wistar rats that were given either a high fructose (10% in drinking water) or a tap water for 21 days. Fructose groups also received minocycline or TRAM-34 systemically for 21 days. We measured systolic and diastolic blood pressure (SBP and DBP), heart rate (HR) periodically with tail-cuff; proinflammatory cytokines and insulin levels in plasma via ELISA, and neuroinflammatory markers in the nucleus tractus solitarii (NTS) by qPCR at the end of 21 days. We also examined endothelium-dependent hyperpolarization (EDH)-type vasorelaxations in isolated mesenteric arteries of the rats ex vivo. SBP, DBP, and HR increased in the fructose group. Both minocycline and TRAM-34 significantly prevented these increases. Fructose intake also increased plasma IL-6, IL-1β, TNF-α, and insulin levels, whereas pretreatment with TRAM-34 prevented these increases as well. Iba-1, but not CD86 levels were significantly higher in the NTS samples of fructose-fed hypertensive rats which implied microglial proliferation. EDH-type vasorelaxations mediated by endothelial KCa3.1 attenuated in the fructose group; however, TRAM-34 did not cause further deterioration in the relaxations. TRAM-34 is as effective as minocycline in preventing fructose-induced hypertension without interfering with the EDH-type vasodilation. Furthermore, TRAM-34 relieves high fructose-associated systemic inflammation.

Effects of novel flame retardants tris(1,3-dichloro-2-propyl) phosphate (TDCIPP) and triphenyl phosphate (TPhP) on function and homeostasis in human and rat pancreatic beta-cell lines

Despite the fact that environmental pollution has been implicated in the global rise of diabetes, the research on the impact of emerging pollutants such as novel flame retardants remains limited. In line with the shift towards the use of non-animal approaches in toxicological testing, this study aimed to investigate the effects of two novel flame retardants tris(1,3-dichloro-2-propyl) phosphate (TDCIPP) and triphenyl phosphate (TPhP) in rat (INS1E) and human (NES2Y) pancreatic beta-cell lines. One-week exposure to 1 μM and 10 μM TDCIPP and TPhP altered intracellular insulin and proinsulin levels, but not the levels of secreted insulin (despite the presence of a statistically insignificant trend). The exposures also altered the protein expression of several factors involved in beta-cell metabolic pathways and signaling, including ATP citrate lyase, isocitrate dehydrogenase 1, perilipins, glucose transporters, ER stress-related factors, and antioxidant enzymes. This study has brought new and valuable insights into the toxicity of TDCIPP and TPhP on beta-cell function and revealed alterations that might impact insulin secretion after more extended exposure. It also adds to the scarce studies using in vitro pancreatic beta-cells models in toxicological testing, thereby promoting the development of non-animal testing strategy for identifying pro-diabetic effects of chemical pollutants.

Association of Interleukin-6 gene (rs1800795) variant with waist-hip-ratio and Insulin resistance: A cross-sectional study in adult women

Obesity is a major contributing factor to metabolic disorders and public health problems worldwide. The goal of the current study was to determine if the Interleukin-6 gene rs1800795 variant is linked to waist-hip-ratio (WHR) and insulin resistance (IR) in North Indian adult women. The WHO guidelines were followed by 37 women who had a WHR >0.85 and 35 women who had a WHR <0.85, out of the 72 women who took part in the study. Every adult woman underwent anthropometric measures. Fasting blood glucose, serum Insulin, lipid levels, and IL-6 levels were measured, and IR was computed. The RFLP technique was used to polymorphise the IL-6 gene (174 G>C) variant. The study group's Insulin, HOMA-IR, BMI, lipid profile, TC/HDL ratio, HDL/LDL ratio, and serum IL-6 level were shown to differ significantly from the control. The percentage frequency of the IL-6 mutant genotype GC+CC (89.19%) and mutant allele C (75.68%) was higher in the study group (WHR >0.85). According to the findings, WHR, TC, TG, and HOMA-IR were substantially correlated (all p <0.05) with the mutant genotype GC+CC of the IL-6 174 G>C gene. This study indicates that the IL-6 rs1800795 gene (174 G>C) variant was substantially linked with metabolic risk variables, such as WHR and HOMA-IR.

New Onset Diabetes After COVID 19 (NODAC) is predominantly due to exacerbated Insulin Resistance (IR) rather than beta cell dysfunction: Lessons from tertiary care hospital data during confluence of two epidemics.

To investigate determinants of new onset diabetes after COVID-19 (NODAC) and its recovery at 6 months. This was an observational follow up study conducted from August, 2020 to July, 2023, recruiting patients with preexisting DM and COVID 19 patients with no history of DM. Multivariate regression analysis was used to determine the factors responsible for severity of COVID 19 infection in preexisting DM group. Clinical, laboratory and glycometabolic parameters were estimated at baseline and 6 months in NODAC and euglycemic group to determine the factors responsible for NODAC and its persistence at 6 months. Of 1310 patients, 855 (65.3%) COVID 19 patients were further divided based on their glycemic status: preexisting DM (19%), NODAC (8.5%) and euglycemia (72.5%). Older age and male gender were independent risk factors for severe COVID 19 disease in patients with preexisting diabetes. Prevalence of NODAC in present study was 8.5%. Patients with NODAC had higher mean fasting blood glucose (FBG), random blood glucose (RBG) and HbA1c at baseline as compared to COVID with euglycemic group with no difference in serum C-peptide levels. Female gender, family history of DM, signs of insulin resistance, higher BMI, WHR, HbA1c, serum insulin levels, FBG and RBG predicted persistence of NODAC at 6 months. Preexisting DM is a risk factor for severe COVID 19 disease. Patients with NODAC have evidence of persistence insulin resistance on follow up, underscoring the need for long term glycemic monitoring.

Pancreatic β‑cell apoptosis in type 2 diabetes is related to post‑translational modifications of p53 (Review).

Pancreatic β‑cells are the only cells that synthesize insulin to regulate blood glucose levels. Various conditions can affect the mass of pancreatic β‑cells and decrease insulin levels. Diabetes mellitus is a disease characterized by insulin resistance and chronic hyperglycemia, mainly due to the loss of pancreatic β‑cells caused by an increase in the rate of apoptosis. Additionally, hyperglycemia has a toxic effect on β‑cells. Although the precise mechanism of glucotoxicity is not fully understood, several mechanisms have been proposed. The most prominent changes are increases in reactive oxygen species, the loss of mitochondrial membrane potential and the activation of the intrinsic pathway of apoptosis due to p53. The present review analyzed the location of p53 in the cytoplasm, mitochondria and nucleus in terms of post‑translational modifications, including phosphorylation, O‑GlcNAcylation and poly‑ADP‑ribosylation, under hyperglycemic conditions. These modifications protect p53 from degradation by the proteasome and, in turn, enable it to regulate the intrinsic pathway of apoptosis through the regulation of anti‑apoptotic and pro‑apoptotic elements. Degradation of p53 occurs in the proteasome and depends on its ubiquitination by Mdm2. Understanding the mechanisms that activate the death of pancreatic β‑cells will allow the proposal of treatment alternatives to prevent the decrease in pancreatic β‑cells.

Association of KCNJ11 gene (rs5219) polymorphism with HOMA-IR & HOMA B values in type 2 diabetes mellitus in India: A case-control study

Objectives Type 2 diabetes mellitus (T2DM) is a complex illness that results from either insulin resistance or insufficient insulin, which raises blood sugar levels. Numerous genes interact to influence the secretion of insulin. A gene of great interest is KCNJ11 of subfamily-J, member 11, which functions as an inwardly rectifying ATP-sensitive potassium (KATP) channel in pancreatic beta cells and is involved in glucose-stimulated insulin release. Material & Methods The present case-control study attempts to delineate the genetic impact of KCNJ11 (rs5219) gene polymorphism on the risk of T2DM in the Indian population. It involves 55 patients with type 2 diabetes (fasting plasma glucose of >126 mg/dl, 2-h glucose of >200 mg/dl, or HbA1c level of >6.4%) and 55 healthy controls (fasting plasma glucose of <100 mg/dl, 2-h glucose of <140 mg/dl, or HbA1c level of <6.4%). polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) was used to study KCNJ11 polymorphism through a standard protocol. Enzyme Linked Immunosorbent Assay (ELISA) was used to estimate serum Insulin levels. HOMA-IR & HOMA-β values were calculated. Statistical analysis was done using t-test, Chi-Square test, and One-way analysis of variance (ANOVA) test. Results Serum insulin levels and HOMA-IR values were significantly decreased in cases than in the control group. Logistic regression analysis showed that the frequency of KK genotype in T2DM individuals (21.8%) was higher than the control group (9%) (p = 0.01). Frequency of K allele (38%) in patients was higher than the control group (18%) (p = 0.001). The K allele risk in diabetic patients was 9.9 times higher as compared to controls (p = 0.001, OR 9.9, 95%Cl 0.036–0.36). Homeostatic model assessment β (HOMA-β) values of KK genotype (59.9±27.8315) were lower than that of EK (76.8±33.23) and EE (127.9±44.59) genotypes (p < 0.001). Conclusion The presence of KCNJ11 (rs 5219) gene polymorphism shows a noteworthy correlation with the likelihood of developing T2DM among the North Indian population. K allele is more likely to be present in individuals with T2DM than the control group. Moreover, HOMA-β values of those with the KK genotype were found to be lower than the individuals having EK and EE genotypes.

The relationship between the expression of fibroblast growth factor 19 and insulin-like growth factor 1 in colorectal polyp tissues and the occurrence of colorectal adenomas

Objective: This investigation sought to delineate the associations among colorectal adenomatous polyps, diabetes, and biomolecules involved in glucose metabolism. Method: Data were collected from 40 patients who underwent endoscopic polypectomy at the Endoscopy Department of Shandong Cancer Hospital between June 2019 and September 2021. This cohort included 27 patients with inflammatory polyps and 13 with adenomatous polyps. We assessed fasting insulin (Fins), fasting blood glucose (FBG), and the mRNA expressions of fibroblast growth factor 19 (FGF-19) and insulin-like growth factor 1 (IGF-1) in the polyp tissues. Both univariate and multivariate logistic regression analyses were employed to ascertain the determinants influencing the emergence of adenomatous polyps. From these analyses, a predictive nomogram was constructed to forecast the occurrence of adenomatous polyps, and evaluations on the discriminative capacity, calibration, and clinical utility of the model were conducted. Results: The adenomatous polyp group exhibited markedly elevated levels of glucose, insulin, FGF-19, and IGF-1, with respective concentrations of (8.67±2.70) mmol/L, (12.72±7.69) μU/L, 2.20±1.88, and 1.36±0.69. These figures were significantly higher compared to the inflammatory polyp group, which showed levels of (5.51±0.72) mmol/L, (5.49±2.68) μU/L, 0.53±0.97, and 0.41±0.46, respectively, P=0.001. Multivariate logistic regression revealed that the relative expression of IGF-1 served as an independent risk factor for the development of colorectal adenomatous polyps (OR=5.622, 95% CI:1.085-29.126). The nomogram displayed a C-index of 0.849, indicating substantial discriminative capability. The calibration curve affirmed the model's accuracy in aligning predicted probabilities with actual outcomes, and the clinical decision curve demonstrated thepractical clinical applicability of the model. Conclusions: There was a significant correlation between the occurrence of colorectal adenomatous polyps and glucose metabolic pathways. Individuals with diabetes showed a higher propensity to develop such polyps.

SGLT2 inhibition improves PI3Kα inhibitor–induced hyperglycemia: findings from preclinical animal models and from patients in the BYLieve and SOLAR-1 trials

PurposeAlpelisib plus fulvestrant demonstrated a significant progression-free survival benefit versus fulvestrant in patients with PIK3CA-mutated HR+ /HER2− advanced breast cancer (ABC) (SOLAR-1). Hyperglycemia, an on-target adverse effect of PI3Kα inhibition, can lead to dose modifications, potentially impacting alpelisib efficacy. We report data from preclinical models and two clinical trials (SOLAR-1 and BYLieve) on Sodium glucose cotransporter 2 inhibitor (SGLT2i) use to improve PI3Kα inhibitor–associated hyperglycemia.MethodsHealthy Brown Norway (BN), mild diabetic Zucker diabetic fatty (ZDF), and Rat1-myr-p110α/HBRX3077 tumor–bearing nude rats treated with alpelisib were analyzed for glucose and insulin control with metformin and dapagliflozin (SGLT2i) and alpelisib efficacy. Hyperglycemia adverse events (AEs) were compared between patients receiving SGLT2i with alpelisib (n = 19) and a propensity score–matched cohort not receiving SGLT2i (n = 74) in both trials.ResultsDapagliflozin and metformin in BN and ZDF rats treated with alpelisib normalized blood glucose and reduced insulin levels. No signs of ketosis or drug-drug interaction were observed when metformin and dapagliflozin was administered with alpelisib. Alpelisib antitumor efficacy was maintained when used with dapagliflozin in tumor-bearing rats. Compared with a matched set of patients without SGLT2i, patients receiving SGLT2i had 4.9 and 6.4 times lower rates of grade ≥ 3 hyperglycemia AEs and hyperglycemia AEs resulting in alpelisib dose adjustments, interruptions, or withdrawals, respectively, and a relative reduction in risk of experiencing these AEs (70.6% and 35.7%).ConclusionThese data suggest adding an SGLT2i can effectively manage hyperglycemia, resulting in fewer alpelisib dose modifications and discontinuations in patients with PIK3CA-mutated HR+ /HER2− ABC (SOLAR-1: NCT02437318; BYLieve: NCT03056755).

Evaluation of terpenes rich Hura crepitans extract on glucose regulation and diabetic complications in STZ-induced diabetic rats

The continual increase in global diabetic statistics portends decreased productivity and life spans, thus making it a disease of concern requiring more effective and safe therapeutic options. While several reports on antidiabetic plants, including Hura crepitans, are available, there is still a dearth of information on the holistic antidiabetic properties of H. crepitans and its associated complications. This study evaluated the antidiabetic potential of methanolic extract of Hura crepitans using in vitro, in vivo, and in silico approaches. The extract revealed a dose-dependent in vitro effect, with a 47.97 % and 65.34 % decrease in the fasting blood sugar levels of streptozotocin (STZ) induced diabetic rats at 150 and 300 mg/kg BW, respectively. Likewise, the extract increased serum and pancreatic insulin levels, and significantly ameliorated neuronal oxidative stress and inflammation by reducing the expression levels of cholinesterase, NF-κB, and COX-2 in the brain of hyperglycemic rats. Serum dyslipidemia, liver, and kidney biomarker indices, and hematological alterations in diabetic rats were also significantly attenuated by the extract. Several constituents, mainly terpenes, were identified in the extract. To further predict the drug-likeness, pharmacokinetics, and binding properties of the compounds, in silico analysis was conducted. Ergosta-2,24-dien-26-oicacid,18-(acetyloxy)-5,6-epoxy-4, 22-dihydroxy-1-oxo-,delta.-lactone-4.beta., displayed the highest docking scores for acetylcholinesterase, butyrylcholinesterases, alpha-amylase, and nuclear factor-kB with values of −12.4, −10.9, −10.3, and −9.4 kcal/mol, while ergost-25-ene-6,12-dione,3,5-dihydroxy-, (3.beta.,5.alpha.) topped for cyclooxygenase-2 (-9.0 kcal/mol). The top-ranked compounds also presented significant oral drug-likeness, pharmacokinetics, and safety properties. Altogether, our data provide preclinical evidence of the potential of Hura crepitans in ameliorating diabetes and its associated complications.

A Novel Classification Approach for Retinal Disease Using Improved Gannet Optimization‐Based Capsule DenseNet

ABSTRACTAn unusual condition of the eye called diabetic retinopathy affects the human retina and is brought on by the blood's constant rise in insulin levels. Loss of vision is the result. Diabetic retinopathy can be improved by receiving an early diagnosis to prevent further damage. A cost‐effective method of accumulating medical treatments is through appropriate DR screening. In this work, deep learning framework is introduced for the accurate classification of retinal diseases. The proposed method processes retinal fundus images obtained from databases, addressing noise and artifacts through an improved median filter (ImMF). It leverages the UNet++ model for precise segmentation of the disease‐affected regions. UNet++ enhances feature extraction through cross‐stage connections, improving segmentation results. The segmented images are then fed as input to the improved gannet optimization‐based capsule DenseNet (IG‐CDNet) for retinal disease classification. The hybrid capsule DenseNet (CDNet) classifies disease and is optimized using the improved gannet optimization algorithm to boost classification accuracy. Finally, the accuracy and dice score values achieved are 0.9917 and 0.9652 on the APTOS‐2019 dataset.

Impact of Rice Bran Oil Emulsified Formulation on Digestion and Glycemic Response to Japonica Rice: An In Vitro Test and a Clinical Trial in Adult Men.

To assess the effect of rice bran oil emulsified formulation (EMF) on cooked rice, a single-arm open clinical trial and in vitro testing for digestion and glycemic response were performed. Fifteen Japanese men consumed 200 g of packed rice, cooked with or without EMF. Blood samples were collected 0, 30, 60, and 120 min post-consumption and analyzed for glucose, insulin, and triglyceride levels. Continuous glucose monitoring (CGM) and sensory evaluation were also performed. A two-step in vitro digestion test, simulating gastric and small intestinal digestion was conducted. EMF-added rice group showed higher insulin response levels at 60 min than the placebo group. Stratification of participants with HbA1c ≥ 5.6 or an insulinogenic index ≤ 0.4 revealed a significant reduction in Cmax glucose levels. A significant correlation was observed between venous and CGM blood glucose levels and no significant sensory differences were observed. The in vitro test revealed significantly lower C∞, equilibrium starch concentrations, with EMF. Clinical trial suggests that EMF may stimulate insulin secretion and reduce blood glucose levels in participants with lower insulin responses. In vitro tests suggest that EMF inhibits glycemic digestion. This trial was registered at the UMIN Center (UMIN000053495; registered 31 January 2024).

Pancreatic β-Cell TRAPδ Deficiency Reduces Insulin Production but Improves Insulin Sensitivity.

The translocon-associated protein-δ (TRAPδ) plays a role in insulin biosynthesis within pancreatic β cells. However, its pathophysiological significance in maintaining islet β cell function and glucose homeostasis remains unclear. In this study, we generated a mouse model featuring pancreatic β cell-specific deletion of TRAPδ (TRAPδ βKO). Our findings revealed that TRAPδ βKO resulted in decreased circulating insulin levels in mice fed either a normal chow diet or a high-fat diet. Multiple independent experiments established that, while TRAPδ deletion reduced insulin content in the islets, it had no discernible effect on insulin gene expression, the insulin/proinsulin ratio, or the expression and glycosylation of the prohormone enzymes involved in proinsulin processing. These data suggest that TRAPδ does not play a pivotal role in the transcription of the insulin gene or proinsulin processing. However, untranslocated preproinsulin levels were significantly increased when islets were treated with a proteasomal inhibitor, suggesting that TRAPδ deficiency may hinder preproinsulin translocation, resulting in a rapid degradation of untranslocated preproinsulin that accounts for the decreased insulin production. Remarkably, despite the moderate decrease in circulating insulin levels in TRAPδ βKO mice, their glucose levels remained unaffected, indicating the presence of compensatory mechanisms that help maintain glucose homeostasis. Insulin tolerance tests further revealed improved insulin sensitivity, accompanied by upregulation of phosphorylated AKT in the peripheral tissues of TRAPδ βKO mice. Collectively, these data highlight the important role of TRAPδ in insulin biosynthesis and β cell function. The moderate reduction in circulating insulin appears to promote insulin sensitivity in insulin target tissues.

Protective Effects of Chitosan-Loaded Pomegranate Peel Extract Nanoparticles on Infertility in Diabetic Male Rats.

Diabetes Mellitus (DM) is known to have an impact on the health of the male reproductive system. It is linked to low sperm quality, increased oxidative stress, and an increased generation of reactive oxygen species in the seminal fluid. Pomegranate extract has phenolic compounds and significant protective properties against oxidative stress, male sex hormone disruptions, and sperm abnormalities. The current study aimed to evaluate the effectiveness of Pomegranate Peel Extract Nanoparticles (PPENPs) on male fertility in diabetic rats. DM was induced in rats by intraperitoneal injection of streptozotocin (60 mg/kg). Twenty-four rats were divided into four groups, 6 rats in each group: control, DM, DM+empty NPs (60 mg/kg, orally), and DM+PPENPs (60 mg/kg, orally). Administration of PPENPs increased the levels of insulin, FSH, LH, testosterone, catalase, glutathione reduced, and semen fructose. PPENPs also improved sperm quality, as seen by improvements in sperm morphology, motility, count, and the ability of metabolically active spermatozoa to convert blue resazurin dye to pink resorufin. However, PPENPs decreased levels of glucose, malonaldehyde, nitric oxide, and sperm abnormalities. Also, histological investigation of the PPENPs showed improvement in testis tissue architecture and increased the diameter size of seminiferous tubules and germinative layer thickness. Our investigation proved that the treatment of PPENPs has a protective effect on the reproductive system of male diabetic rats, improving fertility parameters, healthy sperm profiles, and the antioxidant system.

Fluoride-Induced Alterations in the Pancreas of Mammals: A Meta-analysis.

This review explores the diverse effects of fluoride on pancreatic function, encompassing both in vitro and in vivo studies. Fluoride exposure induces notable alterations at the cellular and molecular levels, affecting pancreatic morphology, histology, and enzymatic activity. In vitro studies demonstrate significant inhibition of pancreatic α-amylase activity and apoptosis in pancreatic beta cells. In vivo investigations reveal structural abnormalities in pancreatic cells, including mitochondrial damage, vacuolation, and nuclear damage. Moreover, fluoride exposure disrupts antioxidant enzyme activity, exacerbating oxidative stress and lipid peroxidation. Changes in digestive enzyme activity, such as the inhibition of pancreatic lipase and α-amylase, further contribute to pancreatic dysfunction. Additionally, alterations in hormone secretion, notably insulin levels and disturbed glucose homeostasis, highlight the complex effects of fluoride on the pancreatic endocrine system. These findings underscore fluoride-induced pancreatic toxicity and highlight the need for a comprehensive understanding and mitigation strategies to safeguard pancreatic health.

Use of placental-derived mesenchymal stem cells to restore ovarian function and metabolic profile in a rat model of the polycystic ovarian syndrome

IntroductionPolycystic ovary syndrome (PCOS) is an endocrine and metabolic disturbance that affects many women worldwide and is characterized by chronic anovulation, hyperandrogenism, and ovarian dysfunction. Placenta-derived mesenchymal stem cells (PDMSCs) are derived from the placenta and have advantages over other sources of MSCs in terms of availability, safety, and immunomodulation.Materials and methodsIn this experimental study, twenty female Wistar rats were assigned to four groups (n = 5) including control, sham, PCOS, and PCOS+PDMSCs groups. Then, PCOS was induced in the rats through administering letrozole for 21 days. PDMSCs (1 × 106 cells) were injected through the tail vein. Fourteen days after the cell infusion, evaluation was performed on the number of healthy follicles, corpus luteum, and cystic follicles as well as the levels of testosterone, follicle-stimulating hormone (FSH), luteinizing hormone (LH), fasting blood glucose, fasting insulin, and insulin resistance. Moreover, the serum levels of cholesterol, triglyceride (TG), high-density lipoprotein (HDL), and low-density lipoprotein (LDL) were measured. Liver function was also determined by the evaluation of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels.ResultsThe number of corpus luteum and primordial, primary, secondary, and antral follicles was significantly elevated in the PCOS+PDMSCs group compared to the PCOS group. However, the number of cystic follicles significantly decreased in the PCOS+PDMSCs group. The LH and testosterone levels also decreased significantly, while FSH levels increased significantly in the PCOS+PDMSCs group. The levels of fasting blood glucose, fasting insulin, and insulin resistance notably decreased in the PCOS+PDMSCs group. Moreover, the lipid profile improved in the PCOS+PDMSCs group along with a significant decrease of cholesterol, LDL, and TG and an increase in HDL. The PCOS+PDMSCs group exhibited marked decreases in the AST and ALT levels as well.ConclusionThe results of this study suggest that PDMSCs are a potential treatment option for PCOS because they can effectively restore folliculogenesis and correct hormonal imbalances, lipid profiles and liver dysfunction in a rat model of PCOS. However, further research is needed to establish the safety and effectiveness of PDMSCs for treating PCOS.