Decreased Fasting Blood Glucose Research Articles

Pulmo-protection of long-term swimming exercise via improving insulin sensitivity in monocrotaline-induced pulmonary hypertensive rats

Exercise has been recognized as an effective intervention in the treatment of pulmonary arterial hypertension (PAH), supported by numerous studies. However, the precise effects of exercise on pulmonary function remain to be fully elucidated. In this study, using a rat model of swimming exercise training and monocrotaline-induced PAH, we aimed to explore its impact on pulmonary morphology and function. Our investigations revealed that MCT-treated rats exhibited augmented mean pulmonary arterial pressure (MPAP) and pulmonary vascular remodeling, which can be attenuated by 4 weeks of swimming exercise training (60 min/day, 5 days/week). Notably, MCT-treated rats showed impaired pulmonary function, as manifested by decreased tidal volume and dynamic compliance, which were reversed by exercise training. Assessment of pulmonary substrate in PAH rats indicated a prominent pro-inflammatory substrate, evidenced by macrophage accumulation through quantitative immunohistological analysis of macrophage-like cell expression (CD68), and extracellular matrix remodeling, evaluated by Masson staining. Importantly, both the pro-inflammatory substrate and extracellular matrix remodeling were ameliorated by swimming exercise training. Additionally, serum biochemical analysis demonstrated elevated levels of low-density lipoprotein cholesterol and Apolipoprotein B following MCT treatment, which were reduced with exercise intervention. Moreover, exercise enhanced systemic insulin sensitivity in both MCT-treated and untreated rats. Notably, MCT and exercise treatment both decreased fasting blood glucose (FBG) levels in rats, whereas exercise training reinstated FBG levels to normal in MCT-treated rats. In summary, our study suggests that swimming exercise confers a pulmonary protective effect in MCT-induced PAH rats, highlighting the potential importance of exercise-based rehabilitation in the management of PAH.

Evaluation of the Effectiveness of In-Hospital Exercise Rehabilitation in Middle-Aged and Elderly Patients with Type 2 Diabetes Mellitus Combined with Sarcopenia Effect of Lifestyle Management on Disease Status in Patients with Type 2 Diabetes Mellitus.

The aim of this study was to explore the effects of in-hospital exercise rehabilitation on glucose and lipid metabolism and healthy physical fitness in middle-aged and elderly patients with type 2 diabetes mellitus (T2DM) combined with sarcopenia, and to provide a reference for the effective implementation of exercise rehabilitation for middle-aged and elderly patients with T2DM combined with sarcopenia in healthcare institutions. This study retrospectively included 122 patients with T2DM combined with sarcopenia treated at the General Hospital of Ningxia Medical University from August 2017 to August 2020 and randomly divided into a control group and an experimental group. The control group was given conventional treatment and the experimental group was given exercise rehabilitation in the hospital for 12 weeks to compare the indexes related to glucose and lipid metabolism and healthy fitness in the two groups. After the intervention, the experimental group showed significant decreases in fasting blood glucose (FBG), glycated hemoglobin (HbA1c), insulin resistance index (HOMA-IR), triglycerides (TG), total cholesterol (TC), low-density cholesterol (LDL-C) and body fat percentage (p < 0.05), while high-density cholesterol (HDL-C), grip strength, lower limb extension, lower limb flexion, peak oxygen uptake were significantly higher (p < 0.05) and were more significant at 12 weeks compared to the 6-week intervention (p < 0.05). However, there were no significant changes in any of the glucose metabolism indicators in the control group before and after the intervention. A two-way repeated measures ANOVA showed that at control baseline levels, HbA1c decreased significantly in the experimental group after both 6 and 12 weeks of intervention compared to the control group (p < 0.05). After 6 weeks of intervention, the experimental group showed a significant decrease in body fat percentage and a significant increase in grip strength. After 12 weeks of intervention, the experimental group showed an increase in glycemic control from 33.3% to 73.3%, a significant decrease in body fat percentage and a significant increase in grip strength, lower limb extension and lower limb flexion strength and peak oxygen uptake. In-hospital exercise rehabilitation can effectively improve the glycemic and lipid profiles of patients with T2DM combined with sarcopenia and enhance their health fitness, with good clinical rehabilitation effects.

Development of 1 Month Sustained-Release Microspheres Containing Liraglutide for Type 2 Diabetes Treatment.

Liraglutide has been extensively applied in the treatment of type 2 diabetes mellitus (T2DM), but its 11-15 h half-life resulted in daily administration, which led to poor patient compliance. This study aimed to solve this problem by developing liraglutide-loaded microspheres with a 1 month sustained release prepared by the W1/O/W2 method combined with the premix membrane emulsification technique to improve therapeutic efficacy. Remarkably, we found that the amphiphilic properties of liraglutide successfully reduced the oil-water interfacial tension, resulting in a stable primary emulsion and decreasing the level of drug leakage into the external water phase. As a result, exceptional drug loading (>8%) and encapsulation efficiency (>85%) of microspheres were achieved. Furthermore, the uniformity in microsphere size facilitated an in-depth exploration of the structural characteristics of liraglutide-loaded microspheres. The results indicated that the dimensions of the internal cavities of the microspheres were significantly influenced by the size of the inner water droplets in the primary emulsion. A denser and more uniform cavity structure decreased the initial burst release, improving the release process of liraglutide from the microspheres. To evaluate the release behavior of liraglutide from microspheres, a set of in vitro release assays and in vivo pharmacodynamics were performed. The liraglutide-loaded microspheres effectively decreased fasting blood glucose (FBG) levels and hemoglobin A1c (HbA1c) levels while enhancing the pancreatic and hepatic functions in db/db mice. In conclusion, liraglutide sustained-release microspheres showed the potential for future clinical applications in the management of T2DM and provided an effective therapeutic approach to overcoming patient compliance issues.

Capsaicin reduces blood glucose and prevents prostate growth by regulating androgen, RAGE/IGF-1/Akt, TGF-β/Smad signalling pathway and reversing epithelial-mesenchymal transition in streptozotocin-induced diabetic mice.

Type 2 diabetes mellitus (T2DM) is a metabolic disease. Diabetes increases the risk of benign prostatic hyperplasia (BPH). Capsaicin is extracted from chili peppers and possesses many pharmacological properties, including anti-diabetic, pain-relieving, and anti-cancer properties. This study aimed to investigate the effects of capsaicin on glucose metabolism and prostate growth in T2DM mice and uncover the related mechanisms. Mice model of diabetes was established by administering a high-fat diet and streptozotocin. Oral administration of capsaicin for 2weeks inhibited prostate growth in testosterone propionate (TP)-treated mice. Furthermore, oral administration of capsaicin (5mg/kg) for 2weeks decreased fasting blood glucose, prostate weight, and prostate index in diabetic and TP-DM mice. Histopathological alterations were measured using hematoxylin & eosin (H&E) staining. The protein expression of 5α-reductase type II, androgen receptor (AR), and prostate-specific antigen (PSA) were upregulated in diabetic and TP-DM mice, but capsaicin reversed these effects. Capsaicin decreased the protein expression of p-AKT, insulin-like growth factor-1 (IGF-1), IGF-1R, and the receptor for advanced glycation end products (RAGE) in diabetic and TP-DM mice. Capsaicin also regulated epithelial-mesenchymal transition (EMT) and modulated the expression of fibrosis-related proteins, including E-cadherin, N-cadherin, vimentin, fibronectin, α-SMA, TGFBR2, TGF-β1, and p-Smad in TP-DM mice. In this study, capsaicin alleviated diabetic prostate growth by attenuating EMT. Mechanistically, capsaicin affected EMT by regulating RAGE/IGF-1/AKT, AR, and TGF-β/Smad signalling pathways. These results provide with new therapeutic approach for treating T2DM or T2DM-induced prostate growth.

Tempeh-Based Supplement Decreases Blood Glucose Levels Through Inhibiting Rage and NF-κB Activity in Type 2 Diabetes Mellitus Mice Model

Objective: Hyperglycemia promotes inflammation through inducing the formation of AGE products, which bind with receptor AGE (RAGE) products in cell membranes, leading to the activation of necrosis factor–kappa beta (NF-κB). This study aimed to analyze the effects of tempeh-based supplement (TBS) preparations of γ-amino butyric acid (GABA) tempeh against mRNA expressions of RAGE and NF-κB on the pancreas of a type 2 diabetes mellitus (DM) mice model. Material and Methods: This research was a quasi-experiment, with pre and post-tests with a control design for blood glucose levels; and post-test only utilizing control for mRNA RAGE and NF-κB expressions. A total of 30 male mice, 8-10 weeks old, weighing 20-25 g were divided into 6 treatment groups: non-diabetic, Diabetic, Diabetic+metformin, Diabetic+TBS 10 mg/100 g BW, Diabetic+TBS 20 mg/100 g BW, and Diabetic+TBS 40 mg/100 g BW. STZ induction once a day for two days was preceded by NA to create a DM mice model; meanwhile, TBS was administrated once a day for 21 days.Results: The mean difference of fasting glucose levels in the diabetic+TBS 40 mg/100 g BW group was the highest when compared to the diabetic group (159.52±1.85) mg/dL. One-way ANOVA revealed statistically significant differences in fasting glucose levels, RAGE and NF-κB expressions in the Diabetic+TBS group at various dosage levels compared to the diabetic control group. Relative mRNA expressions of RAGE and NF-κB were downregulated in the treatment group compared to the diabetic control group. Conclusion: TBS can decrease fasting blood glucose levels and downregulate relative mRNA expressions of RAGE and NF-κB in type 2 DM mice.

Plantaginis semen ameliorates diabetic kidney disease via targeting the sphingosine kinase 1/sphingosine-1-phosphate pathway

Ethnopharmacological relevancePlantaginis Semen (PS) is widely utilized as a common herb in several Asian countries, particularly China, due to its diuretic, anti-hypertensive, anti-hyperlipidemic, and anti-hyperglycemic properties. Furthermore, it is acknowledged for its ability to mitigate renal complications associated with metabolic syndrome. Despite its extensive usage, there is limited systematic literature elucidating its therapeutic mechanisms, thus emphasizing the necessity for comprehensive investigations in this field. AimThis study aims to comprehensively evaluate the therapeutical potential of PS in treating diabetic kidney disease (DKD) and to elucidate the underlying mechanisms through in vivo and in vitro models. MethodsThe main composition of PS were characterized using the UPLC-QTOF-MS method. For the in vivo investigation, a mouse model mediated by streptozocin (STZ) associated with a high-fat diet (HFD) and unilateral renal excision was established. The mice were split into 6 groups (n = 8): control group (CON group), DKD group, low-dose of Plantago asiatica L. seed extract group (PASE-L group, 3 g/kg/d), medium-dose of PASE group (PASE-M, 6 g/kg/d), high-dose of PASE group (PASE-H, 9 g/kg/d), and positive drug group (valsartan, VAS group, 12 mg/kg/d). After 8 weeks of treatment, the damage induced by DKD was evaluated by using relevant parameters of urine and blood. Furthermore, indicators of inflammation and factors associated with the SphK1-S1P signaling pathway were investigated. For the in vitro study, the cell line HBZY-1 was stimulated by high glucose (HG), they were then co-cultured with different concentrations of PASE, and the corresponding associated inflammatory and sphingosine kinase 1/sphingosine-1-phosphate (SphK1-S1P) factors were examined. ResultsA total of 59 major components in PS were identified, including flavonoids, iridoids, phenylethanol glycosides, guanidine derivatives, and fatty acids. In the mouse model, PS was found to significantly improve body weight, decrease fasting blood glucose (FBG) levels, increased glucose tolerance and insulin tolerance, improved kidney-related markers compared to the DKD group, pathological changes in the kidneys also improved dramatically. These effects showed a dose-dependent relationship, with higher PASE concentrations yielding significantly better outcomes than lower concentrations. However, the effects of the low PASE concentration were not evident for some indicators. In the cellular model, the high dose of PASE suppressed high glucose (HG) stimulated renal mesangial cell proliferation, suppressed inflammatory factors and NF-κB, and decreased the levels of fibrillin-1(FN-1) and collagen IV(ColIV). ConclusionOur results indicate that PS exerts favorable therapeutic effects on DKD, with the possible mechanisms including the inhibition of inflammatory pathways, suppression of mRNA levels and protein expressions of SphK1 and S1P, consequently leading to reduced overexpression of FN-1 and ColIV, thereby warranting further exploration.

The consumption of walnuts has an impact on decreasing fasting blood glucose levels in individuals with concurrent hyperglycemia and hyperlipidemia: a randomized control trial

Nationally, the prevalence of Diabetes Mellitus (DM) has increased by 0.5%. In 2013, it was approximately 1.5%, rising to 2.0% in 2018. On the other hand, it is known that administering walnut extract can reduce blood sugar levels in diabetic patients. The aim of this study is to determine the effect of walnut consumption on blood sugar levels. The research was conducted experimentally, using a pre-post test control group design. The research sample consisted of mothers with fasting blood sugar levels ≥200 mg/dL and total cholesterol levels ≥200 mg/dL (hyperglycemic and hyperlipidemic). The total sample size was 50 mothers, divided into 2 groups. Samples were selected using simple random sampling. The intervention involved giving 50 grams of walnut (Canarium Indicum L.) daily for 8 weeks to the treatment group. The research was conducted in the working area of the Paccerakang Community Health Center in Makassar City, Indonesia. Statistical analysis was performed using paired T-tests. There was a decrease in fasting blood glucose levels in the treatment group from 244.12 mg/dL to 195.52 mg/dL. In the control group, there was a slight decrease in blood sugar levels from 236.92 mg/dL to 229.96 mg/dL. Paired T-test analysis in the treatment group showed a value of p=0.00, indicating a significant difference in cholesterol levels before and after the intervention in the treatment group. In the control group, the value was p=0.07, indicating no significant difference in cholesterol levels in the control group. Administering 50 grams of walnuts per day for 8 weeks significantly lowered fasting blood sugar levels in hyperlipidemic and hyperglycemic mothers.

Compositional profiling and bioefficacy studies of pulses-supplemented isocaloric designer biscuits for recently diagnosed diabetic individuals

This study addresses global concerns about diabetes mellitus by exploring a novel approach to manage hyperglycemia through pulses-supplemented designer biscuits. Control and designer biscuits were prepared with varying proportions of wheat flour and pulses (chickpea, mungbean). The pulses-supplemented biscuits exhibited increased protein content and reduced readily available carbohydrates. Selected designer biscuits, with 12.5 % incorporation of chickpea and mungbean pulse flour, demonstrated significantly lower glycemic index (69.17 ± 5.01) and higher satiety index (122.19 ± 8.85) compared to control biscuits. These showed 13 % less glycemic index and 9 % higher satiety index as compared to control biscuits. A four-week bio-efficacy trial involving diabetic subjects consuming these biscuits as a routine snack resulted in an 11.45 % decrease in fasting blood glucose and a 19.15 % reduction in random blood glucose levels. Insulin and HDL levels also significantly improved. The study concludes that these designer biscuits possess a hypoglycemic effect, offering a potential dietary intervention for managing diabetes.

The effect of EKORMIN on rats with diabetes mellitus model: effectiveness on fasting blood glucose, MDA, and insulin levels

Antioxidant use for additional diabetes mellitus therapy is growing, such as okra (Abelmoschus esculentus) and turmeric (Curcuma longa), which are rich in flavonoids and have beneficial effects on diabetes mellitus. This study aimed to determine the effects of okra turmeric extract (EKORMIN) on Fasting Blood Glucose (FBG), malondialdehyde (MDA), and insulin levels in diabetic rats. The research was conducted from December to January 2022 at PSPG UGM using experimental research with a pre-posttest-controlled group design. White male Wistar rats (n = 35) randomly grouped into five: negative control (STZ-NA), positive control (STZ-NA+metformin 1,8 mg/200 gBW), P1 (STZ-NA+EKORMIN low dose 130,5;110,5 mg/kgBW), P2 (STZ-NA+EKORMIN moderate dose 261;221 mg/kgBW), P3 (STZ-NA+EKORMIN high dose 522;442 mg/kgBW). The intervention lasted 14 days. Data analysis was performed using one-way analysis of variance statistical tests and post hoc follow-up tests. EKORMIN in all doses, EKORMIN reduced FBG and MDA levels and increased insulin levels (p&lt;0,05). P2 and P3 were not significantly different from the metformin (PG) group (p&gt;0,05). The decrease in FBG (-167,05±-2,8 vs -175,86±-1,4 mg/dL) and MDA levels (-6,32±0,33 vs -7,98±0,07 nmol/ml) P3 was higher than P2. Similarly for increased insulin levels (121,47±3,03 and 164,09±4,48 pg/ml). EKORMIN was effective in reducing FBG and MDA levels and increased insulin levels in diabetic rats. EKORMIN has antidiabetic effects and has potential for type 2 diabetes mellitus treatment.

Yunvjian decoction mitigates hyperglycemia in rats induced by a high-fat diet and streptozotocin via reducing oxidative stress in pancreatic beta cells

Ethnopharmacological relevanceYunvjian (YNJ), a traditional Chinese herbal formula first reported in Jing Yue Quan Shu, is commonly used in the clinical treatment of type 2 diabetes mellitus (T2DM). However, the mechanism by which YNJ affects T2DM remains unclear. Aim of the studyThis study aimed to assess the therapeutic effects of YNJ on T2DM and explore the potential mechanism involved. Materials and methodsHigh-performance liquid chromatography (HPLC) was used to identify the chemical compounds of YNJ. The anti-T2DM effects of YNJ were observed in a high-fat diet/streptozotocin induced rat model. The type 2 diabetic rats were prepared as follows: rats were fed a high-fat diet for four weeks and then intraperitoneally injected with a low dose (30 mg/kg) of streptozotocin. YNJ and the positive control metformin were used in these experiments. Biochemical assays were implemented to determine the fasting blood glucose, glucose tolerance, insulin sensitivity, serum lipid levels, and oxidative stress index of the pancreas. Hematoxylin-eosin (H&E) staining was used to assess histopathological alterations in the pancreas. The mechanism by which YNJ affects T2DM was evaluated in INS-1 cells treated with glucose and high sodium palmitate. YNJ-supplemented serum was used in these experiments. Methyl thiazolyl tetrazolium assays, enzyme-linked immunosorbent assays, Nile red staining, flow cytometric analysis, and Western blotting were used to assess apoptosis, insulin secretion, lipid accumulation, reactive oxygen species production, and protein levels. ResultsFive major compounds were identified in YNJ. In high-fat diet/streptozotocin-induced diabetic rats, YNJ-M notably decreased fasting blood glucose and lipid levels; ameliorated glucose tolerance, insulin sensitivity, and islet morphology; reduced Malondialdehyde levels; and restored superoxide dismutase activity in the pancreatic islets. Furthermore, the effect of YNJ-M was significantly greater than that of YNJ-L, and YNJ-H had little effect on diabetic rats. In vitro experiments revealed that YNJ-supplemented serum (10%, 15%, and 20%) dramatically suppressed apoptosis, mitigated intracellular lipid accumulation and reduced intracellular oxidative stress levels in a dose-dependent manner. Additionally, YNJ-supplemented serum increased the protein expression of Nuclear factor erythroid 2-related factor 2, Heme oxygenase-1, and superoxide dismutase 1 and inhibited the protein expression of Kelch-like ECH-associated protein 1. ConclusionYNJ ameliorates high-fat diet/streptozotocin induced experimental T2DM. The underlying mechanism involves reducing oxidative stress in pancreatic beta cells. The findings of this study provide scientific justification for the application of the traditional medicine YNJ in treating T2DM.

A kidney-targeted chitosan-melanin nanoplatform for alleviating diabetic nephropathy through modulation of blood glucose and oxidative stress

Diabetic nephropathy (DN) is a serious complication in patients with diabetes, whose expansion process is closely related to oxidative stress caused by hyperglycemia. Herein, we report a chitosan-targeted dagliflozin-loaded melanin nanoparticle (CSMDNPs) that can selectively accumulate in injured kidneys, reduce blood glucose, and alleviate the oxidative stress-induced damage. CSMDNPs possess good dispersion and physiological stability, responsive release at acidic pH, and strong scavenging activities for various reactive oxygen and reactive nitrogen radicals. Moreover, in vitro experiments confirm that CSMDNPs have good biocompatibility, enable targeted uptake in NRK-52E renal tubular cells, and also well alleviate high glucose-induced oxidative stress. In the STZ-induced DN model, CSMDNPs exhibit high targeting distribution and retention in the damaged kidneys of DN mice according to photoacoustic imaging. At the end of CSMDNPs treatment, DN mice show a decrease in fasting blood glucose and a return to near-normal urine and blood indices. H&E, PAS, and masson pathological staining also indicates that CSMDNPs significantly inhibit the expansion of renal interstitium, glycogen, and collagen deposition, showing excellent therapeutic effects. In addition, melanin acts as both drug carrier and antioxidant without exogenous carrier introduction, exhibiting better biosafety and translational prospects.

Gracilaria extract reduce hyperglycemia by modulating gut microbial and short chain fatty acids

High blood sugar is the main feature of diabetes. In order to effectively regulate blood glucose levels, in this study, we used Gracilaria as raw material and found that 70% ethanol extract of Gracilaria (GE) and complex protease hydrolysate of Gracilaria (GH) were beneficial for decreasing fasting blood glucose, improving insulin resistance, enhancing the function of islet β-cells, and regulating the abnormal increase of TC, TG, LDL-c caused by hyperglycemia in diabetic mice. Moreover, 70% ethanol extract of Gracilaria (GE) and complex protease hydrolysate of Gracilaria (GH) affected the gut microbiota structure of diabetic mice, decreased the Firmicutes/Bacteroidetes ratio, increased the abundance of Lactobacillus and Collinsella etc. and reduced the abundance of Helicobacter and Oscillibacter etc. In addition, the content of acetic acid and butyric acid in metabolites of short-chain fatty acids had increased, which had the effect of regulating blood glucose level. The results have showed that 70% ethanol extract of Gracilaria (GE) and complex protease hydrolysate of Gracilaria (GH) are potential marine foods for maintaining blood sugar health.

Comparative Efficacy and Safety of Tirzepatide in Asians and Non-Asians with Type2 Diabetes Mellitus: A Systematic Review and Meta-Analysis.

Tirzepatide is a novel hypoglycemic agent for type2 diabetes mellitus (T2DM). However, the pathophysiology of T2DM in Asians is different from that in non-Asians, and there is no evidence to explain the differences in the efficacy and safety of tirzepatide between different races. A literature search was conducted in China National Knowledge Infrastructure (CNKI), PubMed, Cochrane Library, Clinical Trials.gov, and Embase databases for clinical studies of tirzepatide for T2DM. The data extraction process was done independently by two authors. All analyses were performed using STATA 14.0 software and Review Manager 5.3 software. A total of 2118 patients with T2DM from 6 studies were involved, with doses of tirzepatide ranging from 5 to 15mg administered subcutaneously once weekly. The results showed that compared with control/placebo, tirzepatide was more effective in decreasing fasting blood glucose (FBG) in non-Asians than in Asians, and 10mg rather than 15mg was the optimal dose to decrease FBG. Similarly, non-Asians were more effective than Asians in improving glycated hemoglobin (HbA1c). Asians were significantly more effective than non-Asians in reducing body weight and ≥ 5% weight loss. In terms of adverse events, the incidence of gastrointestinal adverse events was higher in Asians than in non-Asians at the same dose, while the incidence of metabolic and nutrition disorders was higher in non-Asians than in Asians. Tirzepatide is a novel agent for the treatment of diabetes and has different efficacy in Asians and non-Asians. Asians were more likely to experience weight loss and gastrointestinal adverse events, whereas non-Asians were more likely to have better glycemic control and more metabolic and nutritional disorders. PROSPERO registration no. CRD42023489588.

Clinical, genetic profile and therapy evaluation of 11 Chinese pediatric patients with Fanconi-Bickel syndrome

BackgroundFanconi-Bickel syndrome (FBS) is a rare autosomal recessive disorder characterized by impaired glucose and galactose utilization as well as proximal renal tubular dysfunction.MethodsClinical, biochemical, genetic, treatment, and follow-up data for 11 pediatric patients with FBS were retrospectively analysed.ResultsHepatomegaly (10/11), short stature (10/11) and hypophosphataemic rickets (7/11) were the most common initial symptoms. At diagnosis, all patients had decreased fasting blood glucose (FBG), plasma bicarbonate (HCO3−) and serum phosphorus, as well as elevated liver transaminases, alkaline phosphatase (AKP) and proximal renal tubular dysfunction. Two infant patients were misdiagnosed with transient neonatal diabetes mellitus. After therapy with uncooked cornstarch and conventional rickets treatment, remission of hepatomegaly was observed in all patients, with significant improvements in pre-prandial blood glucose, liver transaminases, triglyceride, plasma HCO3− and AKP (p < 0.05). At the last follow-up, 5/7 patients with elevated AKP had nephrocalcinosis. The mean height standard deviation score (Ht SDS) of eight patients with regular treatment increased from − 4.1 to -3.5 (p = 0.02). Recombinant human growth hormone (rhGH) was administered to 4/9 patients, but their Ht SDS did not improve significantly (p = 0.13). Fourteen variants of the SLC2A2 gene were identified, with six being novel, among which one was recurrent: c.1217T > G (p.L406R) (allele frequency: 4/22, 18%). Patients with biallelic missense variants showed milder metabolic acidosis than those with null variants. Two of five patients from nonconsanguineous families with rare homozygous variations showed 5.3 Mb and 36.6 Mb of homozygosity surrounding the variants, respectively; a region of homozygosity (ROH) involving the entire chromosome 3 covering the SLC2A2 gene, suggesting uniparental disomy 3, was detected in one patient.ConclusionsEarly diagnosis of FBS is difficult due to the heterogeneity of initial symptoms. Although short stature is a major issue of treatment for FBS, rhGH is not recommended in FBS patients who have normal GH stimulation tests. Patients with biallelic null variants may require alkali supplementation since urine bicarbonate loss is genetically related. ROH is a mechanism for rare homozygous variants of FBS in nonconsanguineous families.

Effects of DPP4 Inhibitors as Neuroprotective Drug on Cognitive Impairment in Patients with Type 2 Diabetes Mellitus: A Meta-Analysis and Systematic Review.

Type 2 diabetes mellitus is considered as one of the risk factors for cognitive impairment. DPP4 inhibitors are effective drugs for the treatment of type 2 diabetes mellitus. However, the relationship between DPP4 inhibitors and cognitive dysfunction remains unclear. Therefore, we used a meta-analysis to determine the association between DPP4 inhibitors and cognitive impairment in type 2 diabetes mellitus. We systematically searched PubMed, CNKI, and the Cochrane Library at the time of establishment, 2022, and then made inclusion criteria and screened strategies to identify studies with more precise correlations. We included 10 studies with 5,583 participants. The data showed that DPP4 inhibitors significantly reduced the incidence rate of cognitive impairment in type 2 diabetes mellitus (SMD: 0.99; 95% CI [0.59, 1.38]). Furthermore, there was a linear correlation found between cognitive impairment in type 2 diabetes mellitus and fasting blood glucose, 2-hour postprandial blood glucose, and glycosylated hemoglobin. DPP4 inhibitors decreased fasting blood glucose (FPG) (SMD: 0.52; 95% CI [-0.68, -0.37]), blood glucose (2hPPG) at 2 hours after the meal (SMD: 0.82; 95% CI, [-1.2, -0.43]), and HbA1c (SMD: 0.34; 95% CI [-0.48, -0.21]). All data were statistically significant (P < 0.0001). Furthermore, we conducted subgroup analyses of the following measures at various treatment durations and ages: cognitive scores, fasting blood glucose, glycosylated hemoglobin, and two-hour postprandial blood glucose. DPP4 inhibitors significantly improved type 2 diabetic mellitus individuals' cognitive impairment and reduced fasting blood glucose, 2-hour postprandial blood glucose, and glycosylated hemoglobin. Subgroup analysis showed that people aged 60 to 70 years had better treatment effects at 0-180 days. This trial is registered with CRD42023399473.

Lung molecular and histological changes in type 2 diabetic rats and its improvement by high-intensity interval training

BackgroundType 2 diabetes (T2D) leads to serious respiratory problems. This study investigated the effectiveness of high-intensity interval training (HIIT) on T2D-induced lung injuries at histopathological and molecular levels.MethodsForty-eight male Wistar rats were randomly allocated into control (CTL), Diabetes (Db), exercise (Ex), and Diabetes + exercise (Db + Ex) groups. T2D was induced by a high-fat diet plus (35 mg/kg) of streptozotocin (STZ) administration. Rats in Ex and Db + Ex performed HIIT for eight weeks. Tumor necrosis factor-alpha (TNFα), Interleukin 10 (IL-10), BAX, Bcl2, Lecithin, Sphingomyelin (SPM) and Surfactant protein D (SPD) levels were measured in the bronchoalveolar lavage fluid (BALF) and malondialdehyde (MDA) and total antioxidant capacity (TAC) levels were measured in lung tissue. Lung histopathological alterations were assessed by using H&E and trichrome mason staining.ResultsDiabetes was significantly associated with imbalance in pro/anti-inflammatory, pro/anti-apoptosis and redox systems, and reduced the SPD, lecithin sphingomyelin and alveolar number. Performing HIIT by diabetic animals increased Bcl2 (P < 0.05) and IL10 (P < 0.01) levels as well as surfactants components and TAC (P < 0.05) but decreased fasting blood glucose (P < 0.001), TNFα (P < 0.05), BAX (P < 0.05) and BAX/Bcl2 (P < 0.001) levels as well as MDA (P < 0.01) and MDA/TAC (P < 0.01) compared to the diabetic group. Furthermore, lung injury and fibrosis scores were increased by T2D and recovered in presence of HIIT.ConclusionThese findings suggested that the attenuating effect of HIIT on diabetic lung injury mediated by reducing blood sugar, inflammation, oxidative stress, and apoptosis as well as improving pulmonary surfactants components.Graphical Type 2 diabetes increased inflammation, oxidative stress and apoptosis and reduced pulmonary surfactants , while high intensity training improved these negative effects

Anti-Obesity Effects of GABA in C57BL/6J Mice with High-Fat Diet-Induced Obesity and 3T3-L1 Adipocytes.

Obesity is the excessive accumulation of body fat resulting from impairment in energy balance mechanisms. In this study, we aimed to investigate the mechanism whereby GABA (γ-aminobutyric acid) prevents high-fat diet-induced obesity, and whether it induces lipolysis and browning in white adipose tissue (WAT), using high-fat diet (HFD)-fed obese mice and 3T3-L1 adipocytes. We demonstrated that GABA substantially inhibits the body mass gain of mice by suppressing adipogenesis and lipogenesis. Consistent with this result, histological analysis of WAT demonstrated that GABA decreases adipocyte size. Moreover, we show that GABA administration decreases fasting blood glucose and improves serum lipid profiles and hepatic lipogenesis in HFD-fed obese mice. Furthermore, Western blot and immunofluorescence analyses showed that GABA activates protein kinase A (PKA) signaling pathways that increase lipolysis and promote uncoupling protein 1 (UCP1)-mediated WAT browning. Overall, these results suggest that GABA exerts an anti-obesity effect via the regulation of lipid metabolism.

Anti-diabetic mechanism and potential bioactive peptides of casein hydrolysates in STZ/HFD-induced diabetic rats.

Casein hydrolysates have attracted much interest as anti-diabetic food, but their hypoglycemic mechanism and biopeptides are not well understood. This study aimed to explore the anti-diabetic mechanism and potential biopeptides of casein hydrolysates in streptozotocin/high-fat-diet-induced diabetic rats and HepG2 cells. Oral administration of casein hydrolysate prepared with papain-Flavourzyme combination (P-FCH) decreased fasting blood glucose, improved oral glucose tolerance, and reduced HbA1c values in diabetic rats. P-FCH was ineffective in alleviating insulin resistance (homeostasis model assessment and insulin sensitivity index) and enhancing hepatic insulin signaling transduction (phosphorylated Akt, hexokinase activity, and pyruvate kinase activity) in diabetic rats. However, P-FCH significantly upregulated adenosine monophosphate-activated protein kinase phosphorylation and glucose transporter-2 expression, inhibited phosphoenolpyruvate carboxylase kinase activity, and elevated glycogen content in liver tissue of diabetic rats. Furthermore, P-FCH increased glucose consumption independently in normal and insulin-resistant HepG2 cells without the presence of insulin. The peptide composition of P-FCH was characterized. The potential biopeptides in P-FCH showed the sequence characteristic of a Val at the N-terminal or a Pro at the P2 position, and the hypoglycemic activity of Val-Pro-Leu-Gly (the most potential biopeptide in P-FCH) was verified by oral glucose tolerance test in mice. These results suggested that activation of the non-insulin-mediated AMPK pathway might be the determinant mechanism of P-FCH on the hypoglycemic effect. The novel peptide Val-Pro-Leu-Gly in P-FCH was effective in reducing blood glucose levels when orally administered to mice. © 2023 Society of Chemical Industry.

A systematic review and meta-analysis of animal and human studies demonstrates the beneficial effects of Kaempferia parviflora on metabolic syndrome and erectile dysfunction

Kaempferia parviflora (KP) has traditionally been used for centuries to promote health and well-being. Scant evidence is available to explain the relationship between KP and metabolic syndrome and impotence. We sought to test the hypothesis that administration of KP extract enriched with active ingredients, such as polymethoxyflavone, could improve metabolic syndrome, erectile dysfunction, and related outcomes in in vivo. We performed a systematic review and meta-analysis to evaluate the in vivo effects of KP extract on metabolic syndrome, erectile dysfunction, and related outcomes. Studies from 4 databases (i.e., PubMed, Scopus, Embase, and Cochrane Library) were searched from inception up to December 2022. Animal experiment studies and randomized controlled trials comparing KP extract to a placebo control were retrieved and analyzed using RevMan 5.4.1 software. The effect estimate was presented as the standardized mean difference along with its 95% confidence interval (CI). Of 664 articles, a total of 57 articles met our prespecified criteria. KP extract significantly decreased fasting blood glucose in both animal and human studies with standardized mean difference of –0.88 (95% CI, –1.63 to –0.14) and –0.51 (95% CI, –0.98 to –0.05), respectively. Furthermore, KP extract also markedly improved sexual function and physical performance. In sum, KP extract is shown to have effects beneficial to metabolic syndrome, erectile dysfunction, and physical performance.

Study of the influence of GLP-1 receptor agonists on the metabolic activity of the intestinal microbiota in patients with type 2 DM

The aim: to investigate the peculiarities of the metabolic activity of the intestinal microbiota in patients with type 2 diabetes under the influence of glucagon-like peptide-1 receptor agonist therapy. Materials and methods: 21 patients with type 2 diabetes mellitus were included in the study, the average age was 57.2±8.53 years (M±SD), the HbA1c level was 8.29±0.88 % (M±SD). Patients were prescribed raGLP-1 at the maximum tolerated dose for 6 months. Before and after the course of treatment, indicators of body composition were determined by the bioelectrical impedance method (TANITA BC-545N analyzer, Japan), characteristics of carbohydrate metabolism and the lipid spectrum of blood serum, as well as the concentration of GLP-1, trimethylamine-N-oxide (TMAO) by the immunoenzymatic method, of short-chain fatty acids (SCFA) by the method of chromatographic research. Results. After 6 months of therapy with liraglutide against the background of a statistically significant decrease in fasting blood glucose and HbA1c levels (p&lt;0.05), a decrease in body mass index and waist circumference (p&lt;0.05), a decrease in the content of visceral (p&lt;0.05 ) and total fat (p&lt;0.05) in patients with type 2 diabetes, there was a decrease in the concentration of TMAO in blood serum (p&lt;0.05) and an increase in the concentration of SCFA: acetic, propionic (p&lt;0.05) in the coprofiltrate and a tendency to increase in the level of butyric acids. Data analysis also established an increase in the concentration of endogenous GLP-1 in the blood (p&lt;0.05). Conclusions. The detected changes in microbial metabolites may indicate a positive effect of raGLP-1 on the composition of the intestinal microbiota and its metabolic activity in patients with T2DM, which in turn contributes to the improvement of endogenous secretion of incretins