Strategy For Treatment Of Diabetes Research Articles

The role of SLC7A11 in diabetic wound healing: novel insights and new therapeutic strategies

Diabetic wounds are a severe complication of diabetes, characterized by persistent, non-healing ulcers due to disrupted wound-healing mechanisms in a hyperglycemic environment. Key factors in the pathogenesis of these chronic wounds include unresolved inflammation and antioxidant defense imbalances. The cystine/glutamate antiporter SLC7A11 (xCT) is crucial for cystine import, glutathione production, and antioxidant protection, positioning it as a vital regulator of diabetic wound healing. Recent studies underscore the role of SLC7A11 in modulating immune responses and oxidative stress in diabetic wounds. Moreover, SLC7A11 influences critical processes such as insulin secretion and the mTOR signaling pathway, both of which are implicated in delayed wound healing. This review explores the mechanisms regulating SLC7A11 and its impact on immune response, antioxidant defenses, insulin secretion, and mTOR pathways in diabetic wounds. Additionally, we highlight the current advancements in targeting SLC7A11 for treating related diseases and conceptualize its potential applications and value in diabetic wound treatment strategies, along with the challenges encountered in this context.

Monitoring cysteine changes and assessing ferroptosis in diabetic mice with a lysosome-targeted near-infrared fluorescence probe

Diabetes, characterized by elevated blood sugar levels, often leads to various complications. Cysteine (Cys), a biomarker of oxidative stress, is crucial in the progression of diabetes and its complications. Unfortunately, up until now, fluorescent probes for imaging lysosomal Cys in diabetic mouse models have not been available. Ferroptosis, linked to antioxidant damage in the lysosomal Cys/GPX4 axis, plays a significant role in diabetes. Visualizing lysosomal Cys is vital for assessing ferroptosis and understanding diabetes. We introduce a new near-infrared (NIR) fluorescent probe, NIR-Lys-Cys, designed to detect lysosomal Cys in living cells and diabetic mouse models. This probe shows exceptional selectivity and sensitivity towards Cys, along with superior fluorescence characteristics, enabling detection of Cys in living cells. NIR-Lys-Cys can monitor ferroptosis and its inhibition by measuring lysosomal Cys levels and has been used to detect ferroptosis in glucose-induced diabetic cells. It revealed significantly lower Cys concentrations in the livers of diabetic mice compared to healthy controls. Administering antidiabetic medication increased Cys production in diabetic mice. These findings highlight the potential of NIR-Lys-Cys as a tool for elucidating the role of Cys in lysosome-related diseases, providing critical insights into diagnosis and treatment strategies for diabetes and its complications.

Pink1 gene: a key player in the pathophysiology of type 2 diabetes mellitus

Type 2 diabetes mellitus (T2DM) is a complicated metabolic condition with insulin resistance and poor glucose metabolism. Emerging evidence indicates the significance of (PTEN-induced putative kinase 1 (Pink1) in the progression of diseases. Pink1 encodes a protein kinase, which regulates and maintains mitochondrial activity, this mostly affects mitophagy and energy generation. Mutations in the Pink1 gene have been associated to oxidative stress, mitochondrial malfunction, and impaired cellular energy output. The presence of insulin resistance and T2DM may be caused by each of these characteristics. To understand Pink1 potential function in the development of diabetes, this review paper investigates the molecular mechanisms through which it influences glucose metabolism and insulin signaling. Based on preclinical investigations, there is potential for developing innovative therapeutic strategies that specifically target Pink1. These strategies could aim to regulate insulin resistance, improve glucose metabolism, and preserve beta-cell function among individuals diagnosed with diabetes. The following areas of research include figuring out how precisely Pink1 functions in diabetes, translating preclinical findings into clinical settings, exploring precision medicine approaches that specifically target Pink1, and identifying possible therapeutic targets within the Pink1 pathway. This review aims to enhance our understanding of Pink1 impact on T2DM and develop personalized treatments for metabolic disorders. Furthermore, it underscores the significance of persisting with this type of investigation to enhance diabetes treatment strategies.

A Review of Antidiabetic Medicinal Plants as a Novel Source of Phosphodiesterase Inhibitors: Future Perspective of New Challenges Against Diabetes Mellitus.

Intracellular glucose concentration plays a crucial role in initiating the molecular secretory process of pancreatic β-cells through multiple messengers and signaling pathways. Cyclic nucleotides are key physiological regulators that modulate pathway interactions in β -cells. An increase of cyclic nucleotides is controled by hydrolysed phosphodiesterases (PDEs), which degrades cyclic nucleotides into inactive metabolites. Despite the undeniable therapeutic potential of PDE inhibitors, they are associated with several side effects. The treatment strategy for diabetes based on PDE inhibitors has been proposed for a long time. Hence, the world of natural antidiabetic medicinal plants represents an ideal source of phosphodiesterase inhibitors as a new strategy for developing novel agents to treat diabetes mellitus. This review highlights medicinal plants traditionally used in the treatment of diabetes mellitus that have been proven to have inhibitory effects on PDE activity. The contents of this review were sourced from electronic databases, including Science Direct, PubMed, Springer Link, Web of Science, Scopus, Wiley Online, Scifinder and Google Scholar. These databases were consulted to collect information without any limitation date. After comprehensive literature screening, this paper identified 27 medicinal plants that have been reported to exhibit anti-phosphodiesterase activities. The selection of these plants was based on their traditional uses in the treatment of diabetes mellitus. The review emphasizes the antiphosphodiesterase properties of 31 bioactive components derived from these plant extracts. Many phenolic compounds have been identified as PDE inhibitors: Brazilin, mesozygin, artonin I, chalcomaracin, norartocarpetin, moracin L, moracin M, moracin C, curcumin, gallic acid, caffeic acid, rutin, quercitrin, quercetin, catechin, kaempferol, chlorogenic acid, and ellagic acid. Moreover, smome lignans have reported as PDE inhibitors: (+)-Medioresinol di-O-β-d-glucopyranoside, (+)- Pinoresinol di-O-β-d-glucopyranoside, (+)-Pinoresinol-4-O-β-d-glucopyranosyl (1→6)-β-dglucopyranoside, Liriodendrin, (+)-Pinoresinol 4'-O-β-d-glucopyranoside, and forsythin. This review provides a promising starting point of medicinal plants, which could be further studied for the development of natural phosphodiesterase inhibitors to treat diabetes mellitus. Therefore, it is important to consider clinical studies for the identification of new targets for the treatment of diabetes.

Anti-Obesity and Anti-Diabetic Effects of Ostericum koreanum (Ganghwal) Extract.

"Ganghwal" is a widely used herbal medicine in Republic of Korea, but it has not been reported as a treatment strategy for obesity and diabetes within adipocytes. In this study, we determined that Ostericum koreanum extract (OKE) exerts an anti-obesity effect by inhibiting adipogenesis and an anti-diabetic effect by increasing the expression of genes related to glucose uptake in adipocytes and inhibiting α-glucosidase activity. 3T3-L1 preadipocytes were differentiated for 8 days in methylisobutylxanthine, dexamethasone, and insulin medium, and the effect of OKE was confirmed by the addition of 50 and 100 µg/mL of OKE during the differentiation process. This resulted in a reduction in lipid accumulation and the expression of PPARγ (Peroxisome proliferator-activated receptor γ) and C/EBPα (CCAAT enhancer binding protein α). Significant activation of AMPK (AMP-activated protein kinase), increased expression of GLUT4 (Glucose Transporter Type 4), and inhibition of α-glucosidase activity were also observed. These findings provide the basis for the anti-obesity and anti-diabetic effects of OKE. In addition, OKE has a significant antioxidant effect. This study presents OKE as a potential natural product-derived material for the treatment of patients with metabolic diseases such as obesity- and obesity-induced diabetes.

Advancing diabetes treatment: the role of mesenchymal stem cells in islet transplantation.

Diabetes mellitus, a prevalent global health challenge, significantly impacts societal and economic well-being. Islet transplantation is increasingly recognized as a viable treatment for type 1 diabetes that aims to restore endogenous insulin production and mitigate complications associated with exogenous insulin dependence. We review the role of mesenchymal stem cells (MSCs) in enhancing the efficacy of islet transplantation. MSCs, characterized by their immunomodulatory properties and differentiation potential, are increasingly seen as valuable in enhancing islet graft survival, reducing immune-mediated rejection, and supporting angiogenesis and tissue repair. The utilization of MSC-derived extracellular vesicles further exemplifies innovative approaches to improve transplantation outcomes. However, challenges such as MSC heterogeneity and the optimization of therapeutic applications persist. Advanced methodologies, including artificial intelligence (AI) and single-cell RNA sequencing (scRNA-seq), are highlighted as potential technologies for addressing these challenges, potentially steering MSC therapy toward more effective, personalized treatment modalities for diabetes. This review revealed that MSCs are important for advancing diabetes treatment strategies, particularly through islet transplantation. This highlights the importance of MSCs in the field of regenerative medicine, acknowledging both their potential and the challenges that must be navigated to fully realize their therapeutic promise.

Islet-resident macrophage-derived miR-155 promotes β cell decompensation via targeting PDX1

Chronic inflammation is critical for the initiation and progression of type 2 diabetes mellitus via causing both insulin resistance and pancreatic β cell dysfunction. miR-155, highly expressed in macrophages, is a master regulator of chronic inflammation. Here we show that blocking a macrophage-derived exosomal miR-155 (MDE-miR-155) mitigates the insulin resistances and glucose intolerances in high-fat-diet (HFD) feeding and type-2 diabetic db/db mice. Lentivirus-based miR-155 sponge decreases the level of miR-155 in the pancreas and improves glucose-stimulated insulin secretion (GSIS) ability of β cells, thus leading to improvements of insulin sensitivities in the liver and adipose tissues. Mechanistically, miR-155 increases its expression in HFD and db/db islets and is released as exosomes by islet-resident macrophages under metabolic stressed conditions. MDE-miR-155 enters β cells and causes defects in GSIS function and insulin biosynthesis via the miR-155-PDX1 axis. Our findings offer a treatment strategy for inflammation-associated diabetes via targeting miR-155.

Aerobic training with moderate or high doses of vitamin D improve liver enzymes, LXRα and PGC-1α levels in rats with T2DM

Dysregulation of key transcription factors involved in hepatic energy metabolism, such as peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α) and liver X receptor alpha (LXRα), has been observed in T2DM. The present study aims to investigate the effects of aerobic training and vitamin D supplementation on liver enzyme levels and the levels of PGC-1α and LXRα proteins in hepatocytes, in a rat model of T2DM. The study involved 56 male Wistar rats, divided into two groups: one was non-diabetic and acted as a control group (n = 8), and the other had induced diabetes (n = 48). The diabetic rats were then split into six subgroups: two groups received high or moderate doses of vitamin D and aerobic training (D + AT + HD and D + AT + MD); two groups received high or moderate doses of vitamin D alone (D + HD and D + MD); one group underwent aerobic training with vehicle (sesame oil; D + AT + oil), and one group was a diabetic control receiving only sesame oil (oil-receiving). The D + AT + HD and D + HD groups received 10,000 IU of vitamin D, while the D + AT + MD and D + MD groups received 5000 IU of vitamin D once a week by injection. The D + AT + oil group and the sham group received sesame oil. After eight weeks of treatment, body weight, BMI, food intake, serum insulin, glucose, 25-hydroxyvitamin D, ALT, AST, and visceral fat were measured. The levels of PGC-1α and LXRα proteins in the liver was assessed by western blotting. Statistical analysis was performed using the paired t-test, one-way analysis of variance (ANOVA), and the Tukey post hoc test at a significance level of P < 0.05. Body weight, food intake, and BMI decreased significantly in the D + AT + HD, D + AT + MD, D + AT + oil, D + HD, and D + MD groups with the highest reduction being observed in body weight and BMI in the D + AT + HD group. The D + AT + HD group exhibited the lowest levels of insulin, glucose, and HOMA-IR while the D + C group exhibited the highest levels among the diabetic groups. The D + AT + HD and D + AT + MD groups had lower levels of ALT and AST enzymes compared to the other groups with no significant difference between D + AT + HD and D + AT + MD. D + AT + HD (p = 0.001), D + AT + MD (p = 0.001), D + HD (p = 0.023), D + MD (p = 0.029), and D + AT + oil (p = 0.011) upregulated LXRα compared to D + C. Among these groups, D + AT + HD exhibited a more profound upregulation of LXRα than D + AT + MD, D + AT + oil, D + HD, and D + MD (p = 0.005; p = 0.002, p = 0.001, and p = 0.001, respectively). Similarly, D + AT + HD showed a more notable upregulation of PGC-1α compared to D + AT + oil, D + HD, and D + MD (p = 0.002; p = 0.001, and p = 0.001, respectively). Pearson correlation tests showed significant and negative correlations between serum 25-hydroxyvitamin levels and both visceral fat (r = − 0.365; p = 0.005) and HOMA-IR (r = − 0.118; p = 0.009); while positive and significant correlations between the liver-to-bodyweight ratio with both ALT and AST enzymes and also between QUICKI levels with LXRα (r = 0.578; p = 0.001) and PGC-1α (r = 0.628; p = 0.001). Combined administration of aerobic training and vitamin D supplementation potentially improves liver enzymes in type-2 diabetic rats that were simultaneous with upregulating the levels of PGC-1α and LXRα proteins in hepatocytes. These improvements were more significant when combining exercise with high-dose vitamin D supplementation. This study highlights the potential of this combination therapy as a new diabetes treatment strategy.

Investigating Ayurvedic Strategies: An In-Depth Examination of Managing Diabetes across Different Types.

In light of the escalating global concern surrounding diabetes mellitus, contemporary medical practices predominantly hinge on pharmaceutical interventions, accompanied by inherent side effects and enduring limitations. This investigation accentuates a discernible research void regarding the amalgamation of Ayurvedic principles an age-old traditional medical system with prevalent approaches to diabetes management. Despite Ayurveda's promising potential in furnishing a comprehensive and personalized strategy for diabetes treatment, the imperative for further research and collaboration between Ayurvedic practitioners and contemporary healthcare professionals becomes evident. Existing scholarly works underscore the potential advantages of Ayurveda in delivering holistic diabetes care, encompassing not only glycemic control but also fostering overall well-being. Nevertheless, a closer examination reveals specific limitations, challenges, and gaps in current research, necessitating targeted efforts to enable a more exhaustive exploration of Ayurvedic interventions within diabetes management. This comprehensive review scrutinizes Ayurvedic recommendations pertaining to dietary practices, lifestyle adjustments, and herbal therapeutics, shedding light on their plausible efficacy. It serves as a clarion call for heightened research endeavors, aiming to bridge existing gaps and carve a pathway toward an integrated, patientcentric paradigm in diabetes care. In summary, as diabetes prevalence continues to rise globally, the study underscores the limitations of current pharmaceutical-centric approaches and highlights the need for extensive research and collaboration to unlock the full potential of Ayurvedic principles in providing a more holistic and personalized framework for diabetes management. The review navigates through Ayurvedic recommendations, emphasizing the urgency for intensified research efforts to fill existing gaps and pave the way for a seamlessly integrated, patient-focused approach to diabetes care.

Identification and analysis of the expression of genes, involved in insulin signals transmission in the development of experimental type 2 diabetes mellitus

Type 2 diabetes mellitus is a significant concern due to its high prevalence and impact on global health. Ongoing scientific research aims to enhance our understanding of the mechanisms involved in the development and progression of diabetes and devise effective strategies for its treatment. This involves the development of new pharmacological treatments, including novel antidiabetic drugs, and the exploration of individualized approaches to therapy. The mechanisms underlying type 2 diabetes are intricate, involving various aspects of physiology and biochemistry. Gaining insight into the development and progression of type 2 diabetes mellitus through modern laboratory diagnostic methods is crucial for the development of effective treatment and prevention strategies for diabetes. The aim of the study is to identify and analyze a panel of genes, involved in insulin signals transmission in the development of experimental type 2 diabetes mellitus. Materials and methods. The analysis of gene expression involved in insulin signal transmission was conducted using real-time reverse transcription-polymerase chain reaction (RT-qPCR) on the CFX-96 Touch™ system (Bio-Rad, USA). The RT2Profiler™ PCR Array Rat Diabetes kit (QIAGEN, Germany) was employed for this purpose. Results. Based on the study results, the activity of the genes involved in insulin signal transmission can be categorized as follows: genes with low expression compared to the control group of animals, where ∆∆Ct &lt;30 (Akt2, Mapk14, Pik3r1); genes in which no significant changes were detected in the samples compared to the control group (Irs1, Irs2, Pik3cd); no genes with high expression were observed compared to the control group. Conclusions. In the development of experimental type 2 diabetes mellitus, genes involved in insulin signal transmission (Akt2, Mapk14, Pik3r1) exhibited significantly low expression levels (Akt2 – 2.9, Mapk14 – 5.01, Pik3r1 – 8.87) where ∆∆Ct &lt;30, compared to the control group of animals. Conversely, no significant changes were observed in the expression of genes Irs1, Irs2, Pik3cd, also involved in insulin signal transmission, during the development of experimental type 2 diabetes mellitus, compared to the control group of experimental animals.

Diabetes Health Supervision and Treatment Strategy Based on Data Management and Analysis on eKTANG Platform.

The management of diabetes-related risk factors could effectively reduce the occurrence of its complications, improve the quality of life of patients, and reduce the mortality of patients. Data analysis based on the eKTANG platform could greatly improve the efficiency of communication between patients and doctors, and strengthen the treatment and management of diabetes. We created eKTANG to monitor patient health effectively. The eKTANG health management system aims to extensively intervene in blood glucose monitoring, nutrition, exercise, medicine, and health education to enable diabetes patients to achieve optimal treatment results. Diabetes patients diagnosed by Henan University Medical School included through the eKTANG platform were randomly divided into three groups: member service package group, discharge/ outpatient follow-up group, and out-of-hospital care group. We conducted intensive out-ofhospital interventions for three groups of patients for three months to help patients formulate precise blood glucose control plans and conduct training. The traditional group was compared with the eKTANG platform group, and the physiological indicators and patient compliance of the four groups were observed 6 months later. In the eKTANG platform management group, the average blood glucose compliance rate increased significantly, and the percentage of average blood glucose in the range of 3.9-10.0 showed an upward trend. Fasting blood glucose and postprandial blood glucose showed a downward trend. At the same time, the number of patients per capita blood glucose monitoring showed a significant increase compared with the control group. The establishment of the eKTANG platform can improve the efficiency of patient's medical treatment, improve their lifestyles, reduce the incidence of patient complications, and build a virtuous circle gradually. This research has strengthened the health management and autonomy of diabetic patients and improved the efficiency of treatment. It is worthy of promotion.

Predicting early-stage diabetes risk: A machine learning approach

This study evaluates the potential of machine learning algorithms for early-stage diabetes prediction. A dataset containing demographic information, medical history, and lab results was analyzed using Logistic Regression and Random Forest Classifier. The results showed that Random Forest algorithms were able to accurately predict diabetes at an early stage with high accuracy. The best-performing algorithm was found to be the Random Forest Classifier, with an accuracy of 98.0%. These findings suggest that machine-learning algorithms hold great promise for improving diabetes diagnosis and management. The results of this study provide valuable insights for future research in this area and may help inform the development of more effective and efficient screening and treatment strategies for diabetes.

FRI031 A Novel Strategy To Detect Leptin Receptor (Lepr, fa) Mutation In Obesity And Diabetic Animal Model (Zucker Rats)

Abstract Disclosure: X. Xu: None. X. Hu: None. G. Ma: None. T. Wang: None. J. Wang: None. G. Chen: None. L. Zhao: None. J. Chen: None. Globally, diabetes is among the leading causes of premature morbidity and mortality. Early intervention is crucial to achieve optimal outcomes and minimize the burden of diabetes. Animal models are indispensable tools to investigate etiology and explore novel strategies for diabetes treatment and prevention. Zucker strain and its derivatives, Zucker Fatty (ZF) and Zucker Diabetic Fatty (ZDF) rats, are one of the most used rodent models to study diabetes and diabetes-associated metabolic disorders. Homozygous Zucker rats with leptin receptor gene mutation (Lepr, fa-/-) spontaneously develop obesity, hypercholesterolemia, and hyperlipidemia. The wildtype (fa+/+) and heterozygous (fa+/-) littermates phenotypically are indistinguishable. Furthermore, early stages of diabetes are asymptomatic, and the obese phenotype is not appreciable in homogenous (fa-/-) Zucker rats until week 4 of age. Therefore, a rapid, cost-effective, and reliable genotyping method is essential to differentiate homozygous (fa-/-) rats from either wildtype (fa+/+) or heterozygotes (fa+/-) in early interventional studies. We reported a tetra-primer Amplification-Refractory Mutation System (ARMS)—PCR approach to detect leptin receptor fa mutation using genome DNA collected from ear and tail tissues of Zucker rats. Three different types of amplicon patterns are easily identified by agarose gel electrophoresis. Wildtype (fa+/+) genotype displays a 401 bp and a 201 bp amplicon band; heterozygous (fa+/-) consists of a 401 bp, a 263 bp, and a 201 bp amplicon band on the gel; homozygous (fa-/-) comes up with two bands of 401 bp and 263 bp. The genotypes identified by our tetra-primer ARMS—PCR method are further confirmed by sequence analysis. This method requires neither DNA purification nor restriction enzyme digestion, which is suitable for research exploring gene-environment interaction, as well as implementing appropriate intervention approaches in the research areas of diabetes and metabolic diseases. Presentation: Friday, June 16, 2023

Engineering strategies of islet products for endocrine regeneration

Islet transplant has proven to be one promising strategy for diabetes treatment with minimal invasiveness, which restore the patient's endocrine function and avoid exogenous insulin injection. In the past decades, the ever-increasing diabetic population has brought more demand for this technology, therefore, accelerating the development of numerous engineering technologies optimizing the transplantation efficiency. In this review, we summarized the emerging engineering approaches in this field, aiming to provide a general understanding of islet transplantation challenges and the cutting edge of engineering technologies. Firstly, we introduced the islet product sources used for transplantation and analyzed their respective advantages and disadvantages. Afterwards, we focused on the advanced engineering strategies for maintaining islet graft viability and function in the transplantation. Finally, we summarized the engineering challenges and potential research directions in this field.

TheEffects of Eight Weeks of Circuit Resistance Training on Serum METRNL Levels and Insulin Resistance in Individuals with Type 2 Diabetes.

The effects of exercise training on meteorin-like protein (METRNL), one of the newest factors involved, is one of the treatment strategies for diabetes. The present study aimed to investigate the effects of circuit resistance training on METRNL and insulin resistance in people with Type 2 Diabetes Mellitus (T2DM). Twenty eligible diabetics volunteered to participate and were randomly divided into control (n = 10, age = 51 ± 1years, BMI = 27.43 ± 0.98kg/m2) and experimental groups (n = 10, age = 51 ± 1years, BMI = 30.12 ± 0.92kg/m2). The circuit resistance training (10 exercises) used in this study was performed for eight weeks (3 non-consecutive sessions/week, 2-4 circuits, 40%-80% 1RM, 15-6 repetitions). The rest period between each exercise was 20-30s, and the rest between each circuit was 3min. Participants in the control groups were asked to maintain their daily physical activities and not to engage in any systematic training program throughout the study. METRNL did not change significantly in the control group (0.66 ± 0.06 to 0.7 ± 0.04), but it increased significantly in the experimental group (0.3 ± 0.06 to 0.71 ± 0.03, p = 0.001); In contrast, FBS increased significantly in the control group (122.8 ± 7.5 to 192.8 ± 14.9) and decreased significantly in the experimental group (197.2 ± 7.1 to 135.00 ± 14.00, p = 0.001). Insulin in control and experimental groups did not change significantly (p = 0.96); However, the IR of the control group increased significantly (6.37 ± 1.46 to 9.6 ± 1.53), but its level was significantly attenuated in the experimental group (4.89 ± 1.37 to 4.38 ± 1.44, p = 0.028). Eigth weeks of circuit resistance training with low to high intensities can increase the resting levels of METRNL in men with T2DM, which can be significantly associated with the improved fasting blood glucose levels and insulin resistance.

Parkin-mediated mitophagy is negatively regulated by FOXO3A, which inhibits Plk3-mediated mitochondrial ROS generation in STZ diabetic stress-treated pancreatic β cells.

Diabetes mellitus (DM) is one of the most researched metabolic diseases worldwide. It leads to extensive complications such as cardiovascular disease, nephropathy, retinopathy, and peripheral and central nervous system through an inability to produce or respond to insulin. Although oxidative stress-mediated mitophagy has been reported to play an important role in the pathogenesis of DM, specific studies are still lacking as well as remain highly controversial. Here, we found that Parkin-mediated mitophagy in pancreatic β cells under streptozotocin (STZ)-diabetic stress was induced by Polo-like kinase 3 (Plk3) and inhibited by the transcription factor Forkhead Box O3A (FOXO3A). STZ stress induces mitochondrial recruitment of Parkin through Plk3-mediated mitochondrial reactive oxygen species (ROS) generation, which causes pancreatic cell damage. Conversely, FOXO3A acts as negative feedback to prevent diabetic stress by inhibiting Plk3. Meanwhile, antioxidants including N-acetylcysteine (NAC) and natural COA water scientifically block these mitochondrial ROS and mitochondrial recruitment of Parkin by inhibiting Plk3. Through a 3D organoid ex vivo model, we confirmed that not only ROS inhibitors but also mitophagy inhibitory factors such as 3-MA or Parkin deletion can compensate for pancreatic cell growth and insulin secretion under STZ diabetic stress. These findings suggest that the Plk3-mtROS-PINK1-Parkin axis is a novel mitophagy process that inhibits pancreatic β-cell growth and insulin secretion and FOXO3A and antioxidants may provide new alternatives for effective diabetes treatment strategies in the future.

Construction of PLGA Porous Microsphere-Based Artificial Pancreatic Islets Assisted by the Cell Centrifugation Perfusion Technique.

Pancreatic islet transplantation is a promising treatment that could potentially reverse diabetes, but its clinical applicability is severely limited by a shortage of organ donors. Various cell loading approaches using polymeric porous microspheres (PMs) have been developed for tissue regeneration; however, PM-based multicellular artificial pancreatic islets' construction has been scarcely reported. In this study, MIN6 (a mouse insulinoma cell line) and MS1 (a mouse pancreatic islet endothelial cell line) cells were seeded into poly(lactic-co-glycolic acid) (PLGA) PMs via an upgraded centrifugation-based cell perfusion seeding technique invented and patented by our group. Cell morphology, distribution, viability, migration, and proliferation were all evaluated. Results from glucose-stimulated insulin secretion (GSIS) assay and RNA-seq analysis suggested that MIN6 and MS1-loaded PLGA PMs exhibited better glucose responsiveness, which is partly attributable to vascular formation during PM-dependent islet construction. The present study suggests that the PLGA PM-based artificial pancreatic islets may provide an alternative strategy for the potential treatment of diabetes in the future.

Historical perspectives of glucagon’s discovery and early research

Abstract This review article looks at the historical journey of the discovery of glucagon and the initial stages of research that paved the way for a comprehensive understanding of its physiological significance. Glucagon, an essential peptide hormone produced by the pancreas, plays a pivotal role in maintaining glucose homeostasis. Tracing the trajectory of its discovery from its initial identification to the unraveling of its complex functions, this article offers a detailed analysis of the early scientific endeavors, and collaborations that contributed to shaping our understanding of glucagon’s pivotal role. By exploring the historical context, controversies, and advancements, this review sheds light on the evolution of endocrinological knowledge and its profound implications for diabetes research and treatment strategies.

Three-in-one customized bioink for islet organoid: GelMA/ECM/PRP orchestrate pro-angiogenic and immunoregulatory function

Islet organoids open up new strategies for diabetes treatment and pancreatic tissue engineering. Digital light processing (DLP) bioprinting has been extensively applied to the construction of organoids due to its ability to provide precisely patterned scaffolds with fast printing time while specific tailored bioink is indispensable for islet organoid. Customized bioinks that meet different needs were created and frequently applied based on gelatin methacryloyl (GelMA) mixed with other ingredients. Decellularized extracellular matrix (ECM) retains many organic specific structural and functional components and is widespread utilized to reconstruct the native niche like environment. However, considerable cytokines and growth factors were inevitably lost during the decellularized process, while platelet rich plasma (PRP) contains a string of growth factors which often exerted pro-angiogenic role. Therefore, a customized specific bioink for constructing islet organoid based on GelMA, pancreatic ECM and PRP was prepared in our research. In vitro, tube formation assay, CD31 immunofluorescence and relative mRNA expression of vascular genes indicated that the bioink with distinctively promote angiogenesis potential. Macrophages polarization was also conducted, which exhibited superior expression of CD206 (M2 marker) and inferior expression of iNOS (M1 marker). 3D printed organoids maintain the activity of mouse islet β-cells (MIN6) with enhanced glucose sensitivity. In vivo, the results of CD31, CD206 and iNOS immunofluorescence were consistent with that in vitro. In summary, we prepared and characterized specific custom-made bioink with orchestrating immune-regulation response indicated by abundant M2-polarized macrophages, attenuated inflammation, and promoted angiogenesis, which provides an underlying bioink for the fabrication of 3D printed islet organoid.

Role of brain-gut-muscle axis in human health and energy homeostasis.

The interrelationship between brain, gut and skeletal muscle plays a key role in energy homeostasis of the body, and is becoming a hot topic of research. Intestinal microbial metabolites, such as short-chain fatty acids (SCFAs), bile acids (BAs) and tryptophan metabolites, communicate with the central nervous system (CNS) by binding to their receptors. In fact, there is a cross-talk between the CNS and the gut. The CNS, under the stimulation of pressure, will also affect the stability of the intestinal system, including the local intestinal transport, secretion and permeability of the intestinal system. After the gastrointestinal tract collects information about food absorption, it sends signals to the central system through vagus nerve and other channels to stimulate the secretion of brain-gut peptide and produce feeding behavior, which is also an important part of maintaining energy homeostasis. Skeletal muscle has receptors for SCFAs and BAs. Therefore, intestinal microbiota can participate in skeletal muscle energy metabolism and muscle fiber conversion through their metabolites. Skeletal muscles can also communicate with the gut system during exercise. Under the stimulation of exercise, myokines secreted by skeletal muscle causes the secretion of intestinal hormones, and these hormones can act on the central system and affect food intake. The idea of the brain-gut-muscle axis is gradually being confirmed, and at present it is important for regulating energy homeostasis, which also seems to be relevant to human health. This article focuses on the interaction of intestinal microbiota, central nervous, skeletal muscle energy metabolism, and feeding behavior regulation, which will provide new insight into the diagnostic and treatment strategies for obesity, diabetes, and other metabolic diseases.