Beta-cell Research Articles

Metformin Preserves Insulin Secretion in Pancreatic β-cells through FGF21/Akt Pathway In vitro and In vivo.

In our previous studies, it was found that metformin can elevate the expression of FGF21 in the peripheral blood of type 2 diabetic rats and improve insulin sensitivity in diabetic rats. However, whether this effect is mediated by increased FGF21 expression in pancreatic islet β-cells is still unknown. Therefore, this study focuses on the effect of metformin on insulin secretion in pancreatic β-cells. Metformin can effectivly improve insulin resistance. Metformin influencing pancreatic β- cell function is inclusive. In this study, we sought to analyze possible variations in insulin secretion and possible signaling mechanisms after metformin intervention. The study employed an in vivo model of a high-fat diet in streptozocin-induced diabetic rats and an in vitro model of rat pancreatic β-cells (INS-1 cells) that were subjected to damage caused by hyperglycemia and hyperlipidemia. After treating INS-1 cells in normal, high-glucose, and high-glucose+metformin, we measured insulin secretion by glucose-stimulated insulin secretion (GSIS). Insulin was measured using an enzyme-linked immunosorbent assay. FGF21 expression was detected by RT-PCR and Western blot, as well as that p-Akt and t-Akt expression were detected by Western blot in INS-1 cells and diabetic rat islets. Finally, to verify the regulation of the FGF21 /Akt axis in metformin administration, additional experiments were carried out in metformin-stimulated INS-1 cells. High-glucose could significantly stimulate insulin secretion while metformin preserved insulin secretion. Expression of FGF21 and p-Akt was decreased in high-glucose, however, metformin could reverse this effect in INS-1 cells and diabetic rat islets. Our results demonstrate a protective role of metformin in preserving insulin secretion through FGF21/Akt signaling in T2DM.

Vemurafenib inhibits the replication of diabetogenic enteroviruses in intestinal epithelial and pancreatic beta cells

Enteroviruses, which infect via the gut, have been implicated in type 1 diabetes (T1D) development. Prolonged faecal shedding of enterovirus has been associated with islet autoimmunity. Additionally, enteroviral proteins and viral RNA have been detected in the pancreatic islets of individuals with recent-onset T1D, implicating their possible role in beta cell destruction. Despite this, no approved antiviral drugs currently exist that specifically target enterovirus infections for utilisation in disease interventions.Drug repurposing allows for the discovery of new clinical uses for existing drugs and can expedite drug discovery. Previously, the cancer drug Vemurafenib demonstrated unprecedented antiviral activity against several enteroviruses. In the present study, we assessed the efficacy of Vemurafenib and an analogue thereof in preventing infection or reducing the replication of enteroviruses associated with T1D. We tested Vemurafenib in intestinal epithelial cells (IECs) and insulin-producing beta cells. Additionally, we established a protocol for infecting human stem cell-derived islets (SC-islets) and used Vemurafenib and its analogue in this model.Our studies revealed that Vemurafenib exhibited strong antiviral properties in IECs and a beta cell line. The antiviral effect was also seen with the Vemurafenib analogue. SC-islets expressed the viral receptors CAR and DAF, with their highest expression in insulin- and glucagon-positive cells, respectively. SC-islets were successfully infected by CVBs and the antiviral activity of Vemurafenib and its analogue was confirmed in most SC-islet batches.In summary, our observations suggest that Vemurafenib and its analogue warrant further exploration as potential antiviral agents for the treatment of enterovirus-induced diseases, including T1D.

Evaluating the Protective Effect of Melatonin on Atorvastatin-induced Mitochondrial Toxicity in Pancreatic Beta Cells.

Atorvastatin and other statins belong to a category of cholesterollowering drugs, which may cause some damage to pancreatic cells despite their effectiveness. The present study investigated the effects of melatonin against atorvastatin-induced toxicity on islets of Langerhans and CRI-D2 cells. The MTT assay was used to determine cell viability. The effect of various concentrations of melatonin (0,10, 50, 100, 250, 500 and 1000 μM) on CRI-D2 cell viability was evaluated for 24 hours to determine the non-cytotoxic concentrations of melatonin. Additionally, cells were treated with different concentrations of atorvastatin (10, 100, and 150 ng/mL) for 24 hours to determine a concentration that could induce the maximum cell death. After selecting the appropriate concentrations for melatonin, cells were treated with atorvastatin (10, 100, and 150 ng/ml) and melatonin (10 and 100 μM) simultaneously for a period of 24 hours. Malondialdehyde (MDA), reactive oxygen species (ROS), superoxide dismutase, catalase, and glutathione peroxidase activity were assessed as indicators of oxidative stress. To assess mitochondrial function, the ratio of adenosine diphosphate (ADP) to adenosine triphosphate (ATP) and mitochondrial membrane potential (MMP) were measured. Atorvastatin markedly raised ROS and MDA levels. This result was associated with a decrease in MMP, an increase in the ADP/ATP ratio, and a change in the activity of antioxidant enzymes. Atorvastatin (150 ng/mL)-induced mitochondrial damage was alleviated by concurrent melatonin and atorvastatin therapy. These results suggest that melatonin has a protective effect against atorvastatininduced toxicity in the mitochondria of pancreatic cells.

Essential role of germ cell glycerol-3-phosphate phosphatase for sperm health, oxidative stress control and male fertility in mice.

Obesity, diabetes and high-calorie diets are associated with defective sperm function and lowered male fertility. Mature spermatozoa primarily use fructose and glucose, and glucose and glycerol metabolism are important for sperm function. We recently discovered a novel mammalian enzyme, glycerol-3-phosphate (Gro3P) phosphatase (G3PP), and showed that it operates the glycerol shunt by hydrolyzing Gro3P to glycerol, and regulates glucose, lipid and energy metabolism in pancreatic β-cells and liver. We now observed that G3PP expression is the highest in the testis and spermatozoa, and investigated its role in male fertility. We examined G3PP expression during spermatogenesis in mouse and assessed male fertility and spermatozoon function in conditional germ cell specific G3PP-KO (cG3PP-KO) mice and tamoxifen-inducible conditional germ cell G3PP-KO (icG3PP-KO) mice. We also determined the structural and metabolic parameters and oxidative stress in the spermatozoa from icG3PP-KO and control mice. G3PP expression in mouse spermatocytes and spermatids markedly increases during spermatogenesis. Male cG3PP-KO mice, in which germ cell G3PP is deleted from embryonic stage, are infertile due to dysfunctional sperm with reduced motility and capacitation, and elevated spontaneous acrosomal reaction and oxidative stress. However, in icG3PP-KO male mice do not have altered fertility, due to the presence of ∼10% normal spermatozoa. icG3PP-KO spermatozoa display significantly reduced functionality and morphological and ultrastructural alterations. The icG3PP-KO spermatozoa show reduced glycerol production, elevated levels of Gro3P and reactive oxygen species (ROS), and oxidative stress that is associated with increased mitochondrial membrane potential. Germ cell G3PP deletion leads to the generation of spermatozoa that are functionally and structurally abnormal, likely due to the build-up of Gro3P that increases mitochondrial membrane potential, ROS, and oxidative stress and alters spermatozoa function. Overall, the results indicate that G3PP and the glycerol shunt are essential for normal spermatozoa function and male fertility.

Visceral Adipocyte-Derived Extracellular Vesicle miR-27a-5p Elicits Glucose Intolerance by Inhibiting Pancreatic β-Cell Insulin Secretion.

Pancreatic β-cell dysfunction caused by obesity can be associated with alterations in the levels of microRNAs (miRNAs). However, the role of miRNAs in such processes remains elusive. Here, we show that pancreatic islet miR-27a-5p, which is markedly increased in obese mice and impairs insulin secretion, is mainly delivered by visceral adipocyte-derived extracellular vesicles (EVs). Depleting miR-27a-5p significantly improves insulin secretion and glucose intolerance in db/db mice. Supporting the function of EVs' miR-27a-5p as a key pathogenic factor, intravenous injection of miR-27a-5p-containing EVs shows their distribution in mouse pancreatic islets. Tracing the injected AAV-miR-27a-5p (AAV-miR-27a) or AAV-FABP4-miR-27a-5p (AAV-FABP4-miR-27a) in visceral fat results in upregulating miR-27a-5p in EVs and serum, and elicits mouse pancreatic β-cell dysfunction. Mechanistically, miR-27a-5p directly targets L-type Ca2+ channel subtype CaV1.2 (Cacna1c) and reduces insulin secretion in β-cells. Overexpressing mouse CaV1.2 largely abolishes the insulin secretion injury induced by miR-27a-5p. These findings reveal a causative role of EVs' miR-27a-5p in visceral adipocyte-mediated pancreatic β-cell dysfunction in obesity-associated type 2 diabetes mellitus.

Simultaneous Pancreas-Kidney Transplant Outcomes Stratified by Autoantibodies Status and Pretransplant Fasting C-peptide.

Pancreatic beta cell function and islet autoantibodies classically distinguish types of diabetes (type 1 diabetes mellitus [DM] or type 2 DM). Here, we sought to evaluate simultaneous pancreas-kidney (SPK) transplant outcomes stratified by the presence or absence of beta cell function and autoantibodies. SPK recipients were eligible if pretransplant autoantibodies were measured against insulin, islet cell, or glutamic acid decarboxylase 65-kD isoform. Recipients were categorized as A+ or A- based on the detection of ≥1 autoantibodies. Recipients were similarly categorized on the basis of detectable pretransplant fasting C-peptide of ≥2 ng/mL (β+) or <2 ng/mL (β-). Thus, recipients were categorized into 4 groups: A+β-, A-β-, A-β+, and A+β+. Outcomes of interest were overall pancreas graft failure (non-death-censored), death-censored pancreas, or kidney graft failure (death-censored pancreas graft failure [DCGF]; kidney DCGF), composite outcomes with any of the 3 outcomes as pancreas DCGF, use of an antidiabetic agent, or hemoglobin A1c >6.5. One hundred eighty-three SPK recipients were included: A+β- (n = 72), A-β- (n = 42), A-β+ (n = 49), and A+β+ (n = 20). We did not detect a statistical difference in non-death-censored pancreas graft failure for A+β- recipients compared with other groups: A-β- (adjusted hazard ratio [aHR]: 0.44; 95% confidence interval [CI], 0.14-1.42), A-β+ (aHR: 1.02; 95% CI, 0.37-2.85), and A+β+ (aHR: 0.67; 95% CI, 0.13-3.33) in adjusted analyses. Similar outcomes were observed for other outcomes. In SPK recipients, outcomes were similar among recipients with classic features of type 1 DM and various other types of DM.

Environmental Heavy Metal Exposure and Associated Cardiovascular Diseases in Light of the Triglyceride Glucose Index.

Cardiovascular diseases (CVD), primarily ischemic heart disease and stroke, remain leading global health burdens. Environmental risk factors have a major role in the development of CVD, particularly exposure to heavy metals. The Triglyceride Glucose Index (TyG), a measure of insulin resistance and CVD risk, is the primary focus of this study, which summarizes the most recent findings on the effects of lead (Pb), arsenic (As), and cadmium (Cd) on CVD risk. A higher risk of CVD is correlated with an elevated TyG index, which has been linked to insulin resistance. Exposure to Cd is associated with disturbance of lipid metabolism and oxidative stress, which increases the risk of CVD and TyG. Exposure reduces insulin secretion and signaling, which raises the TyG index and causes dyslipidemia. Pb exposure increases the risk of CVD and TyG index via causing oxidative stress and pancreatic β-cell destruction. These results highlight the need of reducing heavy metal exposure by lifestyle and environmental modifications in order to lower the risk of CVD. To comprehend the mechanisms and create practical management plans for health hazards associated with heavy metals, more study is required.

A Perspective On A Promising Role For Caffeine In Modulating The Casr In Pancreatic Β-Cells

The extracellular calcium-sensing receptor (CaSR) is a G-protein-coupled receptor (GPCR) that plays a crucial role in the parathyroid glands and kidneys in maintaining calcium (Ca2+) homeostasis. The extracellular CaSR is present in various cell types not implicated in controlling plasma Ca2+ levels. There is accumulating evidence that CaSR plays a significant role in regulating the function of β-cells in the pancreas. Divalent cations and insulin are released together during exocytosis, and their concentration in the restricted intercellular compartments of the pancreatic islet increases to activate CaSR in neighboring cells. Subsequently, the activated CaSR stimulates insulin vesicle release in the adjacent cells, and by repeating these steps, the signal is amplified in the whole islet. Recent work developed a photoaffinity-tagged glutathione derivative (DAZ-G) as a chemical tool. The study demonstrated that DAZ-G can identify and analyze CaSR ligands. The use of DAZ-G identified caffeine as a positive allosteric modulator of the CaSR, suggesting that the physiological effects of caffeine are partly attributed to its stimulation of the CaSR. Future work may utilize caffeine to activate the CaSR in pancreatic β-cells to improve their secretory function

The general glycan profiling of Dendrobium officinale and their protective effects on MIN6 cells via ERK signaling pathway

Based on structural elucidation of natural and hydrolyzed glycans, the general glycans profiling of D. officinale were unequivocally established for the first time as follows: [Display omitted] The results indicated that the structure of D. officinale glycans with low degree of polymerization (DP ≤ 22) was linear α-D-1,4-glucan, whereas the structure of glycans with high degree of polymerization (DP > 24) was linear acetylated 1,4-glucomannan. The content of acetyl groups and mannose to glucose (M/G) ratio increased with the degree of polymerization of D. officinale glycans. In addition, this study showed that natural D. officinale glycans protected pancreatic β-cell damage induced by glucotoxicity through the extracellular signal–regulated kinase (ERK)1/2 pathway.

Berberine: A Multi-Target Natural PCSK9 Inhibitor with the Potential to Treat Diabetes, Alzheimer's, Cancer and Cardiovascular Disease.

Berberine is a natural product with a wide range of pharmacological effects. It has antimicrobial, anti-cancer, anti-inflammatory, anti-hyperlipidemic, neuroprotective, and cholesterollowering properties, among others. It has been used in traditional Chinese and Ayurvedic medicine for 3000 years and is generally well-tolerated with few side effects. Its main drawback is low oral bioavailability, which has hindered widespread clinical use. However, recent interest has surged with the emergence of evidence that berberine is effective in treating cancer, diabetes, Alzheimer's disease, and cardiovascular disease via multiple mechanisms. It enhances insulin sensitivity and secretion by pancreatic β-cells in Type 2 Diabetes Mellitus in addition to reducing pro-inflammatory cytokines such as IL-6, IL-1β, TLR4 and TNF-α. These cytokines are elevated in Alzheimer's disease, cardiovascular disease, and diabetes. Reductions in pro-inflammatory cytokine levels are associated with positive outcomes such as improved cognition, reduced cardiovascular events, and improved glucose metabolism and insulin sensitivity. Berberine is a natural PCSK9 inhibitor, which contributes to its hypolipidemic effects. It also increases low-density lipoprotein receptor expression, reduces intestinal cholesterol absorption, and promotes cholesterol excretion from the liver to the bile. This translates into a notable decrease in LDL cholesterol levels. High LDL cholesterol levels are associated with increased cardiovascular disease risk. Novel synthetic berberine derivatives are currently being developed that optimize LDL reduction, bioavailability, and other pharmacokinetic properties.

Metformin (The Miracle Drug) Kinetics in Different Diseases such as Cancer

: Metformin, a miracle drug that was introduced a century ago, could be considered for various aspects of diseases such as diabetes (type 1 and 2), cancer prevention or chemotherapy, metabolic and neurodegenerative disease. It is well known that the frequency of cancer is higher in patients with type 2 diabetes mellitus. This review aims to provide updated information regarding clinical pharmacokinetics and the mechanism of action of Metformin in different diseases such as cancer. Diabetes type 1 is another chronic autoimmune disease detected usually in early childhood due to immune-mediated devastation of insulin-producing pancreatic beta-cells. Because of the lack of effective therapeutic approaches, its prevalence is increasing. Regarding cancer, an estimated 19.3 million new cancer cases and almost 10.0 million cancer deaths were reported in 2020 worldwide. By 50-60% bioavailability, the main route of metformin excretion is through urine. Its mechanism of action is based on 1) initiation of adenosine monophosphate-activated kinase, 2) block proinflammatory paths in perivascular adipose tissue, 3) decrease in monocyte-to-macrophage differentiation in vascular tissues, and 4) improvement in endothelial function. Metformin induces adenosine monophosphate-activated protein kinase signaling and suppresses gluconeogenesis. Antitumor properties of Metformin include a decrease in reactive oxygen species generation and inducing autophagy. In addition to glucose-lowering effects, Metformin has moderate anti-inflammatory and antioxidative effects. It could improve lipid profile and reduce overweight individuals' body mass and arterial blood pressure. In type 1 diabetes, Metformin reduces the requirement for daily insulin and improves glycemia. Its long-term use decreases cardiovascular events. In addition to inhibiting the synthesis of lipids via a reduction in oxidative stress, Metformin inhibits inflammation and increases energy metabolism. Finally, by reducing micro- and macro-vascular consequences, mortality-related diabetes and cancer decline by metformin administration. Therefore, in addition to diabetes, Metformin could reduce the proliferation of cancer cells and the possibility of malignancies in different types of cancer.

A 3D-Printed Microdevice Encapsulates Vascularized Islets Composed of iPSC-derived β-like Cells and Microvascular Fragments for Type 1 Diabetes Treatment

Tranplantation of insulin-secreting cells provides a promising method for re-establishing the autonomous blood glucose control ability of type 1 diabetes (T1D) patients, but the low survival of the tranlplanted cells hinder the therapeutic efficacy. In this study, we 3D-printed an encapsulation system contraining β-like cells and microvascular fragments (MVF), to create a retrivable microdevice with vascularized islets in vivo for T1D therapy. The functional β-like cells were differentiated from the urine epithelial cell-derived induced pluripotent stem cells (UiPSCs). Single-cell RNA sequencing provided an integrative study and macroscopic developmental analyses of the entire process of differentiation, which revealed the developmental trajectory of differentiation in vitro follows the developmental pattern of embryonic pancreas in vivo. The MVF were isolated from the epididymal fat pad. The microdevice with a groove structure were rapidly fabricated by the digital light processing (DLP)-3D printing technology. The β-like cells and MVF were uniformly distributed in the device. After subcutaneous transplantation into C57BL/6 mice, the microdevice have less collagen accumulation and low immune cell infiltration. Moerover, the microdevice encapsulated vascularized islets reduced hyperglycemica in 33% of the treated mice for up to 100 days without immunosuppressants, and the humanized C-peptide was also detected in the serum of the mice. In summary, we described the microdevice-protecd vasculared islets for long-term treatment of T1D, with high safety and potential clinical transformative value, and may therefore provide a translatable solution to advance the research progress of β cell replacement therapy for T1D.

Clinical characteristics, treatment, and treatment switch after molecular-genetic classification in individuals with maturity-onset diabetes of the young: Insights from the multicenter real-world DPV registry.

Individuals with maturity-onset diabetes of the young (MODY) are often misdiagnosed as type 1 or type 2 diabetes and receive inappropriate care. We aimed to investigate the characteristics and treatment of all MODY types in a multicenter, real-world setting. Individuals with MODY from the diabetes prospective follow-up (DPV) registry were studied. We compared clinical parameters during the first year of diabetes and the most recent treatment year after MODY diagnosis. A total of 1640 individuals were identified with GCK-MODY (n = 941) and HNF1A-MODY (n = 417) as the most frequent types. Among these, 912 individuals were available with information during the first and the most recent treatment year (median duration of follow-up: 4.2 years [2.6-6.6]). Positive beta cell autoantibodies were present in 20.6% (15.2% IAA). Median age at diagnosis ranged from 9.9 years in GCK-MODY (Q1-Q3: 6.2-13.1 years) and INS-MODY (2.7-13.7 years) to 14.3 years (5.0-17.1) in KCNJ11-MODY. Frequency of oral antidiabetic agents (OAD) use increased and insulin decreased in HNF4A-MODY (OAD: 18% to 39%, insulin: 34% to 23%) and in HNF1A-MODY (OAD: 18% to 31%, insulin: 35% to 25%). ABCC8-MODY was characterized by a decrement in nonpharmacological treatment (26% to 16%) and "insulin only" treatment (53% to 42%), while the proportion of individuals treated with OAD but no insulin increased from 0% to 21%. Our results indicate that some teams caring for individuals with MODY are hesitant with regard to current recommendations. Registries are an essential source of information and provide a basis for discussing treatment guidelines for MODY.

In Silico Analysis of novel Phytocompounds targetting Dipeptidyl peptidase 4 Enzyme: A New Link between Prediabetes and its cardio-metabolic complications

BackgroundDPP-4 inhibitors, are widely used clinically for treatment of Diabetes. Increase in circulating DPP4 levels have been well demonstrated in patients with Type 2 Diabetes mellitus. The present study assessed the contribution of DPP-4 axis to the pathophysiology of Prediabetes and its cardiometabolic complications. In addition, in silico analysis of phytocompounds that target DPP 4 enzyme was undertaken to identify novel Phytocompounds with therapeutic potential in Prediabetes. MethodologyA novel experimental model of Prediabetes coexisting with hypertension and dyslipidemia was developed in experimental rats to elucidate the pathophysiological role of DPP-4 in Prediabetes and its resultant cardio-metabolic sequale. In the Prediabetic rats, DPP-4 levels, lipid profile, blood pressure readings, fasting blood sugar values, insulin resistance, beta cell function were measured and compared to Normal Control group. In addition, the DPP-4 Inhibitory activity of Phytocompounds (Arjunetin, Guggulsterone) was studied by molecular docking studies including Root Mean Square Deviation (RMSD), Root Mean Square Fluctuation (RMSF), DPP 4 binding affinity and Protein-ligand simulation between the DPP4 and the Phytocompounds was performed. Results were compared to Vildagliptin, the synthetic DPP-4 inhibitor and metformin (Glucophage), the standard antidiabetic drug used in clinical settings. ResultsA statistically significant increase (p < 0.001) in DPP-4 levels along with a decline in bea cell function with increase in Insulin resistance was observed in Prediabetic rats. A positive correlation (p < 0.001) between serum DPP-4 with HbA1c, lipids, and systolic blood pressure was found. The novel model of Prediabetes co-existing with hypertension and dyslipidemia was successfully developed and validated. The silico active site interaction data from simulation studies demonstrated that Arjunetin and Guggulsterone shows effective and stable binding with DPP-4. Arjunetin maintains its contact with Glu205, Glu206, and Asn710 and by interacting with Val207 and His740, it effectively occupies the flanking residues of the active site area. Based on their protein-ligand contact report, Vildagliptin maintains its connection through Tyr547 and during simulation, Guggulsterone interacts with Ser630. ConclusionThe current study offers experimental evidence of DPP-4′s causal role in the development of cardio-metabolic consequences (dyslipidemia and hypertension) of Prediabetes. Arjunetin and Guggulsterone are two Phytocompounds whose potential as promising DPP-4 inhibitors has been further documented using in silico molecular docking studies.

A prospective mixed‐methods pilot study of a novel group structured education programme for adults with cystic fibrosis diabetes

AbstractBackground: Cystic fibrosis diabetes (CFD) is associated with increased morbidity and mortality in adults with cystic fibrosis (CF). In addition, poor glycaemic control can result in microvascular complications. Group educational programmes for people with type 1 and 2 diabetes have been shown to improve diabetes outcomes. The national guidelines recommend that people with CFD should receive education regarding diabetes; however, specific CFD group education programmes have not been evaluated.Aims: This study aimed to test whether this novel diabetes contents and intervention for CFD based on the Beta Cell Education Resources for Training in Insulin and Eating (BERTIE) type 1 diabetes education programme was beneficial for adults with CFD. The adapted course, Improved Diabetes Education in Adults with Cystic Fibrosis (IDEA‐CF ), incorporated CFD‐specific topics and was delivered virtually via videoconference group sessions to facilitate peer learning and support without the risk of cross‐infection. A pilot study was conducted utilising this novel IDEA‐CF virtual structured program to ensure that the intervention met the patients’ educational needs.Methods: This randomised controlled multimethods pilot study recruited adults with CFD taking insulin therapy and cared for by a large regional CF centre. After providing written informed consent, the participants completed all the study forms and questionnaires before randomisation. Randomisation was performed using a computerised randomisation system that allocated adults with CFD into the intervention group (IDEA‐CF) or routine care group for the 12‐week study period. Participants who were randomised into the routine group continued to receive one‐on‐one education as before. Using the CF quality‐of‐life (QoL) questionnaire (revised Cystic Fibrosis Questionnaire [CFQ‐R]), outcomes were measured at baseline and 12‐week visits in both groups. The participants in the intervention group were asked to take part in a semistructured qualitative interview after the completion of the intervention, which was performed by a CF psychologist.Results: A total of 20 participants were recruited, with 18 completing the intervention and study follow‐up visits. In the CFQ‐R domains, physical functioning, emotional functioning, eating, role functioning and respiratory symptoms were significantly improved in the intervention group compared with the routine care group. The IDEA‐CF Knowledge Assessing Questionnaire (IDEA‐CF KAQ) scores in the intervention group improved compared with the IDEA‐CF KAQ scores in the control group, suggesting that education improves knowledge and understanding. The IDEA‐CF structured virtual group education group was well received, with participants valuing the educational content and the ability to interact with each other and to learn from their peers’ experiences constructively.Conclusions: Our study demonstrated that the IDEA‐CF education programme improved health‐related QoL and diabetes knowledge, as evidenced by the results of the IDEA‐CF KAQ. The participants valued the educational contents of the programme and reported a positive experience interacting with their peers.

Human peripancreatic adipose tissue paracrine signaling impacts insulin secretion, blood flow, and gene transcription.

Adipose tissue accumulation around non-adipose tissues is associated with obesity and metabolic disease. One relatively unstudied depot is peripancreatic adipose tissue (PAT) that accumulates in obesity and insulin resistance and may impact beta cell function. Pancreatic lipid accumulation and PAT content are negatively related to metabolic outcomes in humans, but these studies are limited by the inability to pursue mechanisms. We obtained PAT from human donors through the Human Pancreas Analysis Program to evaluate differences in paracrine signaling compared to subcutaneous adipose tissue (SAT), as well as effects of the PAT secretome on aortic vasodilation, human islet insulin secretion, and gene transcription using RNAseq. PAT had greater secretion of IFN-γ and most inflammatory eicosanoids compared to SAT. Secretion of adipokines negatively related to metabolic health were also increased in PAT compared to SAT. We found no overall effects of PAT compared to SAT on human islet insulin secretion, however, insulin secretion was suppressed after PAT exposure from men compared to women. Vasodilation was significantly dampened by PAT conditioned media, an effect explained almost completely by PAT from men and not women. Islets treated with PAT showed selective changes in lipid metabolism pathways while SAT altered cellular signaling and growth. RNAseq analysis showed changes in islet gene transcription impacted by PAT compared to SAT, with the biggest changes found between PAT based on sex. The PAT secretome is metabolically negative compared to SAT, and impacts islet insulin secretion, blood flow, and gene transcription in a sex dependent manner.

Review Article : The Effect of Quercetin Compounds on Type II Diabetes Mellitus

The immune system of the body targets the insulin-producing pancreatic cells, which results in diabetes mellitus. Synthesized antidiabetic drugs cause side effects of liver and kidney damage. Quercetin are known to have the same mechanism as synthetic antidiabetic drugs, so it can be an alternative treatment for diabetes. This article is a review with a literature search using PubMed, MDPI and Google Scholar. Quercetin activate AMPK which affects the decrease in blood glucose levels, protect cell damage due to free radicals so as to prevent a decrease in insulin levels and repair tissue damage due to hyperglycemia. Quercetin plays a role in reducing the risk of Type II DM complications. Quercetin compounds affect Type II Diabetes Mellitus with various mechanisms.

Antidiabetic Potential of Mangifera Indica: Insights from In Vitro and In Vivo Studies

Background: Diabetes mellitus is a chronic endocrine disorder characterized by elevated blood glucose levels. Owing to the adverse side effects of synthetic drugs, natural products attract research interest because of their fewer side effects and prominent efficacy. In the present study, we examined the antidiabetic effects of the seeds of Mangifera indica. Materials &amp; Methods: Phytochemical analysis (quantitative and free radical scavenging activity), in vitro enzymatic assays, and in vivo antidiabetic studies were performed on the hydroalcoholic extract of M. indica. Additionally, an immunohistochemistry approach was utilized to illustrate the alteration of the cellular architecture in the pancreatic islets of extract-treated diabetic rats. Results: The hydroalcoholic extract exhibited good phenolic and flavonoid contents, prominent radical scavenging ability, and antidiabetic activity in an in vitro enzymatic assay. At a dose of 200 mg/kg body weight, the hydroalcoholic extract significantly decreased the blood glucose and HbA1c levels and substantially improved the serum marker levels (GLU, ALB, UREA, CREA, CHOL, TG, SGPT, SGOT, TP, HDL, and ALP). The immunohistological study revealed 40% regeneration of pancreatic β-cells upon extract treatment. Conclusion: The hydroalcoholic extract has prominent antidiabetic activity, as evidenced by both in vitro and in vivo studies, by modulating the cellular composition and regenerating the β-cells of the pancreatic islet.

Vector of glycated hemoglobin in the formation of dysglycemia in postmenopause: Emphasis on early diagnosis and therapy

Introduction. The close relationship of postmenopause with insulin resistance (IR) and metabolic syndrome (MetS) marks a high cardiometabolic risk of dysglycemia, determining the need for its early diagnosis and therapy. Pathogenetically substantiated criteria for the diagnosis of prediabetes and the nature of early drug therapy for type 2 diabetes mellitus (T2DM) are debated. Information on the relationship between glucose homeostasis parameters and menopausal MetS is fragmentary.Aim. To evaluate the associations of glycated hemoglobin (HbA1c) levels with indices of IR, β-cell function and MetS character- istics in a cohort of postmenopausal women with different carbohydrate metabolic states.Materials and methods. In 94 Caucasian postmenopausal women 58.0 (53.0; 63.0) years old the following were determined: HbA1c, fasting glycemia (FG), TyG and HOMA2 indices, C-peptid, BMI, waist circumference (WC), blood pressure (BP), triglycerides (TG), HDL-C levels. When classifying women by HbA1c (ADA criteria), 15 had normoglycemia, 24 prediabetes, 55 T2DM. ME (25–75%) was assessed using SPSS (version 17); intergroup differences according to the Mann – Whitney test; Spearman and partial correlation analysis were performed.Results. HbA1c age independently correlated with IR parameters: TyG (R = 0.590; p &lt; 0.001), HOMA2-IR (R = 0.318; p &lt; 0.05) and beta cell function: HOMA2-B (R = -0.355; p &lt; 0.001); with lipid markers of MetS (TG, HDL-C, respectively R = 0.382; -0.448; p &lt; 0.001), anthropometric and blood pressure levels.Conclusion. Associations of HbA1c in postmenopausal women with a spectrum of glucose homeostasis parameters and MetS mark it as a vector of formation and progression of dysglycemia due to a close connection with the functional state of β-cells and the importance of lipoglucotoxicity in the dynamics of postmenopausal IR. The obtained data pathogenetically determine the use of HbA1c in the verification of dysglycemia and the early administration of combined antihyperglycemic therapy aimed at preserving β-cell function. The potential of dipeptidyl peptidase-4 inhibitors in slowing the progression of type 2 diabetes mellitus is considered

Effect of fenofibrate on residual beta cell function in adults and adolescents with newly diagnosed type 1 diabetes: a randomised clinical trial.

Fenofibrate, a peroxisome proliferator-activated receptor alpha agonist, shows some promise in alleviating beta cell stress and preserving beta cell function in preclinical studies of type 1 diabetes. The aim of this phase 2, placebo-controlled, double-blinded, randomised clinical trial was to investigate the efficacy and safety of fenofibrate in adults and adolescents with newly diagnosed type 1 diabetes. We enrolled 58 individuals (aged 16 to 40 years old) with newly diagnosed type 1 diabetes and randomised them to daily oral treatment with fenofibrate 160 mg or placebo for 52 weeks (in a block design with a block size of 4, assigned in a 1:1 ratio). Our primary outcome was change in beta cell function after 52 weeks of treatment, assessed by AUC for C-peptide levels following a 2h mixed-meal tolerance test. Secondary outcomes included glycaemic control (assessed by HbA1c and continuous glucose monitoring), daily insulin use, and proinsulin/C-peptide (PI/C) ratio as a marker of beta cell stress. We assessed outcome measures before and after 4, 12, 26 and 52 weeks of treatment. Blinding was maintained for participants, their healthcare providers and all staff involved in handling outcome samples and assessment. The statistical analyses for the primary outcome included 56 participants (n=27 in the fenofibrate group, after two withdrawals, and n=29 in the placebo group). We found no significant differences between the groups in either 2h C-peptide levels (mean difference of 0.08 nmol/l [95% CI -0.05, 0.23]), insulin use or glycaemic control after 52 weeks of treatment. On the contrary, the fenofibrate group showed a higher PI/C ratio at week 52 compared with placebo (mean difference of 0.024 [95% CI 0.000, 0.048], p<0.05). Blood lipidome analysis revealed that fenofibrate repressed pathways involved in sphingolipid metabolism and signalling at week 52 compared with placebo. The 52 week intervention evoked few adverse events and no serious adverse events. Follow-up in vitro experiments in human pancreatic islets demonstrated a stress-inducing effect of fenofibrate. Contrary to the beneficial effects of fenofibrate found in preclinical studies, this longitudinal, randomised, placebo-controlled trial does not support the use of fenofibrate for preserving beta cell function in individuals with newly diagnosed type 1 diabetes. EudraCT number: 2019-004434-41 FUNDING: This study was funded by the Sehested Hansens Foundation.