Defective Secretion Research Articles

β-cell Jagged1 is sufficient but not necessary for islet Notch activity and insulin secretory defects in obese mice

ObjectiveNotch signaling, re-activated in β cells from obese mice and causal to β cell dysfunction, is determined in part by transmembrane ligand availability in a neighboring cell. We hypothesized that β cell expression of Jagged1 determines the maladaptive Notch response and resultant insulin secretory defects in obese mice. MethodsWe assessed expression of Notch pathway components in high-fat diet-fed (HFD) or leptin receptor-deficient (db/db) mice, and performed single-cell RNA sequencing (scRNA-Seq) in islets from patients with and without type 2 diabetes (T2D). We generated and performed glucose tolerance testing in inducible, β cell-specific Jagged1 gain-of- and loss-of-function mice. We also tested effects of monoclonal neutralizing antibodies to Jagged1 in glucose-stimulated insulin secretion (GSIS) assays in isolated islets. ResultsJag1 was the only Notch ligand that tracked with increased Notch activity in HFD-fed and db/db mice, as well as in metabolically-inflexible β cells enriched in patients with T2D. Neutralizing antibodies to block Jagged1 in islets isolated from HFD-fed and db/db mice potentiated GSIS ex vivo. To demonstrate if β cell Jagged1 is sufficient to cause glucose tolerance in vivo, we generated inducible β cell-specific Jag1 transgenic (β-Jag1TG) and loss-of-function (iβ-Jag1KO) mice. While forced Jagged1 impaired glucose intolerance due to reduced GSIS, loss of β cell Jagged1 did not protect against HFD-induced insulin secretory defects. ConclusionsJagged1 is increased in islets from obese mice and in patients with T2D, and neutralizing Jagged1 antibodies lead to improved GSIS, suggesting that inhibition of Jagged1-Notch signaling may have therapeutic benefit. However, genetic loss-of-function experiments suggest that β cells are not a likely source of the Jagged1 signal.

Vildagliptin inhibits high fat and fetuin-A mediated DPP-4 expression, intracellular lipid accumulation and improves insulin secretory defects in pancreatic beta cells

Dipeptidyl peptidase-4 (DPP-4), a ubiquitous proteolytic enzyme, inhibits insulin secretion from pancreatic beta cells by inactivating circulating incretin hormones GLP-1 and GIP. High circulating levels of DPP-4 is presumed to compromise insulin secretion in people with type 2 diabetes (T2D). Our group recently reported lipid induced DPP-4 expression in pancreatic beta cells, mediated by the TLR4-NFkB pathway. In the present study, we looked at the role of Vildagliptin on pancreatic DPP-4 inhibition, preservation of islet mass and restoration of insulin secretion. MIN6 mouse insulinoma cells incubated with palmitate and fetuin-A, a proinflammatory organokine associated with insulin resistance, showed activation of TLR4-NFkB pathway, which was rescued on Vildagliptin treatment. In addition, Vildagliptin, by suppressing palmitate-fetuin-A mediated DPP-4 expression in MIN6, prevented the secretion of IL-1beta and fetuin-A in the culture media. DPP-4 siRNA abrogated TLR4-NFkB pathway mediated islet cell inflammation. Vildagliptin also reduced palmitate-fetuin-A mediated intracellular lipid accumulation in MIN6 and isolated islets from high fat fed (HFD) mice as observed by Oil O Red staining with downregulation of CD36 and PPARgamma. Vildagliptin also preserved islet mass and rescued insulin secretory defect in HFD mice. Our results suggest that inhibition of DPP-4 by Vildagliptin protects pancreatic beta cells from the deleterious effects of lipid and fetuin-A, preserves insulin secretory functions and improves hyperglycemia.

Loss of the Golgi-localized v-ATPase subunit does not alter insulin granule formation or pancreatic islet β-cell function.

Delayed Golgi export of proinsulin has recently been identified as an underlying mechanism leading to insulin granule loss and β-cell secretory defects in type 2 diabetes (T2D). Because acidification of the Golgi lumen is critical for proinsulin sorting and delivery into the budding secretory granule, we reasoned that dysregulation of Golgi pH may contribute to proinsulin trafficking defects. In this report, we examined pH regulation of the Golgi and identified a partial alkalinization of the Golgi lumen in a diabetes model. To further explore this, we generated a β-cell specific knockout (KO) of the v0a2 subunit of the v-ATPase pump, which anchors the v-ATPase to the Golgi membrane. Although loss of v0a2 partially neutralized Golgi pH and was accompanied by distension of the Golgi cisternae, proinsulin export from the Golgi and insulin granule formation were not affected. Furthermore, β-cell function was well preserved. β-cell v0a2 KO mice exhibited normal glucose tolerance in both sexes, no genotypic difference to diet-induced obesity, and normal insulin secretory responses. Collectively, our data demonstrate the v0a2 subunit contributes to β-cell Golgi pH regulation but suggest that additional disturbances to Golgi structure and function contribute to proinsulin trafficking defects in diabetes.NEW & NOTEWORTHY Delayed proinsulin export from the Golgi in diabetic β-cells contributes to decreased insulin granule formation, but the underlying mechanisms are not clear. Here, we explored if dysregulation of Golgi pH can alter Golgi function using β-cell specific knockout (KO) of the Golgi-localized subunit of the v-ATPase, v0a2. We show that partial alkalinization of the Golgi dilates the cisternae, but does not affect proinsulin export, insulin granule formation, insulin secretion, or glucose homeostasis.

Ethanolic Stem-Bark Extract of Blighia unijugata Possesses Anti-Hyperglycemic and Anti-Hyperlipidemic Activity in a Streptozotocin-Induced Diabetes Model

Introduction: The global rise in the incidence of diabetes mellitus, particularly type 2 diabetes mellitus (T2DM), and its associated complications have become a public health threat. Besides hyperglycemia, hyperlipidemia has been associated with diabetes due to the defect in insulin secretion and/or action. Medicinal plants are being investigated to discover drug alternatives with better efficacies, lesser adverse effects, and cost-effectiveness. This work investigated the anti-hyperglycemic and anti-hyperlipidemic activity of ethanolic stem bark extract of Blighia unijugata (EBU) in streptozotocin (STZ)-induced diabetic Sprague- Dawley (SD) rats.
 Method: T2DM was induced in male SD rats by a single intraperitoneal injection of STZ (50 mg/kg in 0.1 M citrate buffer, pH 4.5) and confirmed 72 hours later. EBU (100 and 200 mg/kg) and glibenclamide (5 mg/kg) were administered orally to the diabetic rats (n = 5) for 28 days. The effect of the treatments on fasting blood glucose (FBG), lipid profile, atherogenic predictor indices, and body weight were assessed.
 Results: EBU treatments significantly reduced (p≤0.001) elevated blood glucose, total cholesterol, triglycerides, and Very Low-Density Lipoprotein cholesterol (VLDL-c, p≤0.001) but increased High-Density Lipoprotein cholesterol (HDL, p≤0.05) compared to the diabetic control. Also, all the atherogenic risk predictor indices were significantly reduced (p≤0.001). In addition, EBU treatment mitigated the significant weight loss (p≤0.01) associated with the diabetic state when compared to the normal control.
 Conclusion: These findings first report the anti-hyperglycemic, anti-hyperlipidemic, and anti-atherogenic properties of the stem bark of ethanolic extract of Blighia unijugata, and can be further studied and used as an anti-diabetic and anti-hyperlipidemic agent.
 Keywords: Blighia unijugata; hyperglycemia; atherogenic index; hyperlipidemia; diabetes

ANGPTL3 deficiency impairs lipoprotein production and produces adaptive changes in hepatic lipid metabolism

Angiopoietin-like protein 3 (ANGPTL3) is a hepatically secreted protein and therapeutic target for reducing plasma triglyceride-rich lipoproteins and low-density lipoprotein (LDL) cholesterol. Although ANGPTL3 modulates the metabolism of circulating lipoproteins, its role in triglyceride-rich lipoprotein assembly and secretion remains unknown. CRISPR-associated protein 9 (CRISPR/Cas9) was used to target ANGPTL3 in HepG2 cells (ANGPTL3−/−) whereupon we observed ∼50% reduction of apolipoprotein B100 (ApoB100) secretion, accompanied by an increase in ApoB100 early presecretory degradation via a predominantly lysosomal mechanism. Despite defective particle secretion in ANGPTL3−/− cells, targeted lipidomic analysis did not reveal neutral lipid accumulation in ANGPTL3−/− cells; rather ANGPTL3−/− cells demonstrated decreased secretion of newly synthesized triglycerides and increased fatty acid oxidation. Furthermore, RNA sequencing demonstrated significantly altered expression of key lipid metabolism genes, including targets of peroxisome proliferator-activated receptor α, consistent with decreased lipid anabolism and increased lipid catabolism. In contrast, CRISPR/Cas9 LDL receptor (LDLR) deletion in ANGPTL3−/− cells did not result in a secretion defect at baseline, but proteasomal inhibition strongly induced compensatory late presecretory degradation of ApoB100 and impaired its secretion. Additionally, these ANGPTL3−/−;LDLR−/− cells rescued the deficient LDL clearance of LDLR−/− cells. In summary, ANGPTL3 deficiency in the presence of functional LDLR leads to the production of fewer lipoprotein particles due to early presecretory defects in particle assembly that are associated with adaptive changes in intrahepatic lipid metabolism. In contrast, when LDLR is absent, ANGPTL3 deficiency is associated with late presecretory regulation of ApoB100 degradation without impaired secretion. Our findings therefore suggest an unanticipated intrahepatic role for ANGPTL3, whose function varies with LDLR status.

Epcam regulates intrahepatic bile duct reconstruction in zebrafish, providing a potential model for primary cholangitis model

Epithelial cell adhesion molecules (EpCAMs) have been identified as surface markers of proliferating ductal cells, which are referred to as liver progenitor cells (LPCs), during liver regeneration and correspond to malignancies. These cells can differentiate into hepatocytes and biliary epithelial cells (BECs) in vitro. EpCAM-positive LPCs are involved in liver regeneration following severe liver injury; however, the in vivo function of EpCAMs in the regenerating liver remains unclear. In the present study, we used a zebrafish model of LPC-driven liver regeneration to elucidate the function of EpCAMs in the regenerating liver in vivo. Proliferating ductal cells were observed after severe hepatocyte loss in the zebrafish model. Analyses of the liver size as well as hepatocyte and BEC markers revealed successful conversion of LPCs to hepatocytes and BECs in epcam mutants. Notably, epcam mutants exhibited severe defects in intrahepatic duct maturation and bile acid secretion in regenerating hepatocytes, suggesting that epcam plays a critical role in intrahepatic duct reconstruction during LPC-driven liver regeneration. Our findings provide insights into human diseases involving non-parenchymal cells, such as primary biliary cholangitis, by highlighting the regulatory effect of epcam on intrahepatic duct reconstruction.

Dynamic regulation of hepatic lipid metabolism by torsinA and its activators.

Depletion of torsinA from hepatocytes leads to reduced liver triglyceride secretion and marked hepatic steatosis. TorsinA is an atypical ATPase that lacks intrinsic activity unless it is bound to its activator, lamina-associated polypeptide 1 (LAP1) or luminal domain-like LAP1 (LULL1). We previously demonstrated that depletion of LAP1 from hepatocytes has more modest effects on liver triglyceride secretion and steatosis development than depletion of torsinA. We now show that depletion of LULL1 alone does not significantly decrease triglyceride secretion or cause steatosis. However, simultaneous depletion of both LAP1 and LULL1 leads to defective triglyceride secretion and marked steatosis similar to that observed with depletion of torsinA. Depletion of both LAP1 and torsinA from hepatocytes generated phenotypes similar to those observed with only torsinA depletion, implying that the 2 proteins act in the same pathway in liver lipid metabolism. Our results demonstrate that torsinA and its activators dynamically regulate hepatic lipid metabolism.

The Protein S Erlangen Mutation PROS1c.1904T>C (F635S) Suppresses Secretion.

The recently identified PROS1 mutation Protein S Erlangen c.1904T>C, resulting in amino acid exchange F635S, is associated with severe quantitative protein S (PS) deficiency and clinical thrombosis. It was hypothesized that this deficiency is due to a secretion defect [1]. This report aims to further elucidate the potential secretion defect of PS Erlangen. Coding sequences (CDS) of wild type (WT) PROS1 (encoding PS) and mutated PROS1c.1904T>C (encoding PSF635S) were cloned in front of the CDS of green fluorescent protein (GFP), and the respective plasmids were introduced into HEK293T cells. PROS1-GFP and PROS1c.1904T>C-GFP expressing HEK293T cell lines were analyzed by confocal laser scanning microscopy and western blot for cellular proteins and proteins secreted to the growth medium. Western blot analysis revealed a significantly reduced secretion of PSF635S compared to WT PS. This observation was confirmed by the detection of mutant PSF635S-GFP fusion exclusively in the endoplasmic reticulum (ER), while PS-GFP passed through the entire secretory pathway, as indicated by the localization within both the ER and Golgi apparatus. The Protein S Erlangen mutation results in type I PS deficiency caused by a secretion defect.

Дифференциальная диагностика гипогликемий, развившихся на фоне врожденного гиперинсулинизма

Congenital hyperinsulinism (CHI) is a genetic disorder characterized by inappropriate insulin secretion by pancreatic b-cells. CHI may induce the development of severe hypoglycemic conditions already in the neonatal period. The causes of neonatal hypoglycemia are diverse; therefore, an accurate algorithm is needed for diagnosis and differential diagnosis of pathological conditions accompanied by hypoglycemia. One of the causes of low blood glucose levels is hyperinsulinism, both exogenous (administration of insulin or its stimulants) and endogenous (autonomous insulin secretion, disorders of the propulsive or endocrine function of the gastrointestinal tract). An increase in insulin levels in the blood due to hypoketonemia is one of the common signs of this condition. In etiopathogenesis, transient and persistent hyperinsulinism are distinguished. The latter is represented by monogenic (genetic defects in insulin secretion) and syndromic (associated with other hereditary diseases) forms. This article presents data on the characteristics of insulin metabolism, possible causes of CHI, and discusses the algorithm for differential diagnosis of neonatal hypoglycemia for timely detection of CHI. Key words: congenital hyperinsulinism, neonatal hypoglycemia, hyperinsulinism-hyperammonemia syndrome, Sotos syndrome, Beckwith–Wiedemann syndrome, Kabuki syndrome, Costello syndrome, congenital disorders of glycosylation

Tratamento de diabetes mellitus tipo 2 em um sagui-de-orelha-preta (Callithrix penicillata)

ABSTRACT: Type-2 diabetes mellitus (T2DM) is characterized by defects in insulin secretion and combined peripheral resistance to the hormone. Several non-human primates (NHP) species develop T2DM, mainly captive animals with reduced physical activity and incorrect feeding. This case report describes the T2DM treatment of a black-eared marmoset (Callithrix penicillata) by diet reformulation and metformin oral administration. An adult female was diagnosed with T2DM after hyperglycemia and high serum fructosamine associated with glycosuria and obesity. Metformin hydrochloride (125mg/animal, orally, q24h) associated with feeding intervention was started. After 26 days, a significant reduction in weight, glycemia, and serum fructosamine could be observed, showing satisfactory results for the adopted therapy. Metformin is considered a safe drug for T2DM treatment due to its low hypoglycemia risk. The new diet consisted of sweet potato, squash, and varied fruits offered twice daily. In addition, thawed-mice newborns, egg whites, and small portions of pelleted primate food. In the present report, metformin use, associated with a low glycemic index diet, was effective in treating this particular marmoset and may present a potential for T2DM treatment in other NHPs.

Endoplasmic reticulum stress in pancreatic β-cell dysfunctionality and diabetes mellitus: a promising target for generation of functional hPSC-derived β-cells in vitro.

Diabetes mellitus (DM), is a chronic disorder characterized by impaired glucose homeostasis that results from the loss or dysfunction of pancreatic β-cells leading to type 1 diabetes (T1DM) and type 2 diabetes (T2DM), respectively. Pancreatic β-cells rely to a great degree on their endoplasmic reticulum (ER) to overcome the increased secretary need for insulin biosynthesis and secretion in response to nutrient demand to maintain glucose homeostasis in the body. As a result, β-cells are potentially under ER stress following nutrient levels rise in the circulation for a proper pro-insulin folding mediated by the unfolded protein response (UPR), underscoring the importance of this process to maintain ER homeostasis for normal β-cell function. However, excessive or prolonged increased influx of nascent proinsulin into the ER lumen can exceed the ER capacity leading to pancreatic β-cells ER stress and subsequently to β-cell dysfunction. In mammalian cells, such as β-cells, the ER stress response is primarily regulated by three canonical ER-resident transmembrane proteins: ATF6, IRE1, and PERK/PEK. Each of these proteins generates a transcription factor (ATF4, XBP1s, and ATF6, respectively), which in turn activates the transcription of ER stress-inducible genes. An increasing number of evidence suggests that unresolved or dysregulated ER stress signaling pathways play a pivotal role in β-cell failure leading to insulin secretion defect and diabetes. In this article we first highlight and summarize recent insights on the role of ER stress and its associated signaling mechanisms on β-cell function and diabetes and second how the ER stress pathways could be targeted in vitro during direct differentiation protocols for generation of hPSC-derived pancreatic β-cells to faithfully phenocopy all features of bona fide human β-cells for diabetes therapy or drug screening.

The Effect of Probiotic Supplementation on the Levels of Biomarkers in Diabetic Animal Model: A Research Protocol

Introduction: Type 2 Diabetes Mellitus (T2DM) is characterised by hyperglycaemia, insulin secretion defects, or resistance. Most T2DM drugs help to improve glycaemic status, but the response varies among individuals. The modern lifestyle with unhealthy eating habits leads to gut dysbiosis. Altered gut microbiota can disrupt the host’s metabolic and signaling pathways, intestinal barrier integrity, and function. Probiotics could restore a healthy microbiota in the intestine, thus improving glycaemic status. Need of the study: Probiotics may assist in re-establishing a healthy microbiota composition in the intestine. Limited studies have evaluated the supplementation of probiotics for effectively managing T2DM. Aim: To investigate the effects of probiotics on biomarker levels in type 2 diabetic male Wistar rats. Materials and Methods: This interventional case-control study will be conducted at the Centre for Toxicology and Developmental Research (CEFTE) at Sri Ramachandra Institute of Higher Education and Research, Chennai, Tamil Nadu, India. The study will involve 46 male Wistar rats divided into five groups. Diabetes will be induced by feeding the animals a High-Fat Diet (HFD) and administering a low dose of Streptozotocin (STZ) injection. Groups 1 and 2 will be on basal and HFDs, serving as negative and positive controls, respectively. Groups 3, 4 and 5 will be the intervention groups. The study duration will be four weeks and three days for diabetes induction and six weeks for intervention. Blood samples will be collected periodically to assess biomarkers, and at the end of the study, internal organs will be harvested for histopathological examination. Institutional Ethics Committee (IEC) approval has been obtained. Categorical variables will be analysed using Chi-square or Fisher’s exact test, while continuous variables will be analysed using repeated measures Analysis of Variance (ANOVA). A p-value of ≤0.05 will be considered statistically significant, and statistical analysis will be performed using Statistical Package for Social Sciences (SPSS) version 16.0.

Flow-chamber device (T-TAS) to diagnose patients suspected of platelet function defects.

Patients suspected of platelet function defects represent a diagnostic challenge for the clinical laboratory, mainly due to the complexity and poor standardization of screening methods. We compared a new flow-based chip-equipped point-of-care (T-TAS) device with lumi-aggregometry and other specific tests. The study included 96 patients suspected of platelet function defects and 26 patients referred to hospital for an evaluation of residual platelet function while on antiplatelet therapy. Forty-eight of 96 patients displayed abnormal platelet function by lumi-aggregometry, and 10 of them had defective granule content and were classified as δ-storage pool disease (δ-SPD). T-TAS compared favorably with lumi-aggregometry in detecting the most severe forms of platelet function defects (i.e., δ-SPD) [test agreement (lumi-light transmission aggregometry [lumi-LTA] vs T-TAS) for the δ-SPD subgroup was 80% and K CHOEN 0.695. T-TAS was less sensitive to milder platelet function defects (i.e., primary secretion defects [PSD]). Concerning patients on antiplatelets, test agreement (lumi-LTA vs T-TAS) in detecting patients who were responders to this therapy was 54%; K CHOEN 0.150. The results indicate that T-TAS can detect the more severe forms of platelet function defects such as δ-SPD. There is limited agreement of T-TAS with lumi-aggregometry in identifying responders to antiplatelets. However, this poor agreement is commonly shared by lumi-aggregometry and other devices owing to the lack of test specificity and of prospective data from clinical trials linking platelet function with therapeutic efficacy.

Oligodendrocyte-derived LGI3 and its receptor ADAM23 organize juxtaparanodal Kv1 channel clustering for short-term synaptic plasticity

Neurodevelopmental disorders, such as intellectual disability (ID), epilepsy, and autism, involve altered synaptic transmission and plasticity. Functional characterization of their associated genes is vital for understanding physio-pathological brain functions. LGI3 is a recently recognized ID-associated gene encoding a secretory protein related to an epilepsy-gene product, LGI1. Here, we find that LGI3 is uniquely secreted from oligodendrocytes in the brain and enriched at juxtaparanodes of myelinated axons, forming nanoscale subclusters. Proteomic analysis using epitope-tagged Lgi3 knockin mice shows that LGI3 uses ADAM23 as a receptor and selectively co-assembles with Kv1 channels. A lack of Lgi3 in mice disrupts juxtaparanodal clustering of ADAM23 and Kv1 channels and suppresses Kv1-channel-mediated short-term synaptic plasticity. Collectively, this study identifies an extracellular organizer of juxtaparanodal Kv1 channel clustering for finely tuned synaptic transmission. Given the defective secretion of the LGI3 missense variant, we propose a molecular pathway, the juxtaparanodal LGI3-ADAM23-Kv1 channel, for understanding neurodevelopmental disorders.

Correlation of Glycated Hemoglobin with Serum Triglyceride to High Density Lipoprotein Ratio in Type 2 Diabetes Mellitus Patients

Introduction: Diabetes mellitus is an endocrine disorder characterized by hyperglycemia. It may be due to a defect in insulin secretion or action or both. Importantly, lipid metabolism is also abnormal in diabetes such as an increment of TG level and reduction in plasma HDL level which is the major cardiovascular risk. Glycated hemoglobin is measured to monitor the long-term glycemic status of the patients.Materials and Methods: The current study is designed retrospectively to find out the correlation between HbA1C and TG to HDL ratio. The data onthe lipid profile of newly diagnosed diabetes mellitus were retrieved from the laboratory software of National Medical College, a tertiary care hospital in Madhesh province, Nepal. The categorical data were expressed in frequency and percentage and continuous data were expressed in mean and standard deviation depending on their distribution. Pearson correlation analysis was used to correlate the glycated hemoglobin and TG to HDL ratio. Results: The current study investigated the diabetic and lipid profile in 604 retrospectively enrolled patients. Out of which 358 (59.3%) were diabetic and 246 (40.7%) were healthy subjects.The comparison of serum lipid levels between diabetes and healthy subjects revealed a significant difference concerningTriglycerides, total cholesterol, HDL, LDL, and VLDL (P value less than 0.05). The correlation analysis revealed a significant positive correlation betweenTG/HDL ratio and glycated hemoglobin (0.09, 0.02).Conclusion: Our results revealed the correlation between HbA1C and TG/ HDL ratio in the Nepalese diabetic population. Hypertriglyceridemia was common in diabetic patients. Elevation of the TG/HDL ratio aggravates the cardiovascular risks in the diabetic patients.

Antioxidant and Antidiabetic Properties of Pectin Extracted from Pomegranate (Punica granatum) Peel

Diabetes mellitus is a chronic disease resulting from defects in insulin secretion, insulin action or both. The prevalence of diabetes has been increasing gradually over the last few decades. It has emerged as a global health concern that burdens public health and socioeconomic development. Oxidative stress plays a crucial role in developing diabetic complications affecting the eyes, kidneys, nerves, and heart. There are various established adverse effects of current conventional antidiabetic drugs. Due to this fact, plants have been chosen for developing new drugs as the bioactive compounds in plants have higher antidiabetic and antioxidant properties with low toxicity. Pomegranate peel is an agro-industrial waste that is rich in pectin. Pectin is a natural polysaccharide that has gained importance due to its pharmacological properties. In this study, pectin from pomegranate peel was extracted using ultrasound-assisted extraction to characterize the pectin and to evaluate its antioxidant and antidiabetic activity. Pomegranate peel pectin (PPP) was extracted using citric acid (solid-to-liquid ratio of 1:30 g/mL) at pH 2 under optimized conditions at 75°C for 40 min. A white sponge-like solid was obtained upon freeze-drying with a yield of 18.17%. The moisture content of pectin was 18.26% and it was found to be a low-methoxylated pectin with a degree of esterification (DE) of 31.07%. Fourier Transform Infrared Spectroscopy (FTIR) results showed that pectin from pomegranate peel was quite similar to commercial pectin. The antioxidant activity was evaluated using scavenging assays, 1,1- diphenyl-2-picrylhydrazyl (DPPH), Ferric Reducing Antioxidant Potential (FRAP) and 2,2′-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) at 1 mg/mL (78.26% with IC50 value of 326.8 μg/mL, 79.12% with IC50 value of 83.63 μg /mL and 442.7 mg Fe2+/g, respectively). The antidiabetic activity was assessed using an α-amylase inhibition assay at 1 mg/mL (43.82%). These results suggest that PPP has the potential to be used as an antidiabetic and antioxidant agents.

Description of the Level of Knowledge and Behavior of Type Two Diabetes Mellitus Patients Regarding Diabetic Foot at Koja Regional Hospital in June 2023

Diabetes mellitus is a group of metabolic diseases characterized by hyperglycemia resulting from defects in insulin secretion, insulin action or both. In the Southeast Asia region, Indonesia is ranked 3rd with a prevalence of 11.3%. Previous studies have shown that the level of knowledge and behavior of type 2 diabetes mellitus patients regarding diabetic foot is still inadequate. This study aims to describe the level of knowledge and behavior of patients with type 2 diabetes mellitus regarding diabetic foot. The research design is descriptive with a cross-sectional approach. The reachable population for this study were all type two diabetes mellitus patients at Koja Hospital who the researchers could meet when conducting the study in June 2023. The sampling technique used was purposive sampling with a sample size of 40 patients. The research subjects were 40 people with type 2 Diabetes Mellitus. The results showed that in terms of knowledge, 50% of sufferers had a high level of knowledge. However, negative behavior is more dominant with a percentage of 57.5%. Although the level of knowledge and type two diabetes mellitus patients about diabetic feet at Koja Hospital in June 2023 is still high, patient behavior is still low, so it is necessary to train and empower health service providers to deliver adequate health messages regarding the prevention of diabetic feet

Research Progress of Diabetic Disease Prediction Model in Deep Learning

Diabetes is a metabolic disease characterized by high blood sugar, which is mostly caused by the defect of insulin secretion or the impairment of its biological function. The persistent high blood sugar in diabetes will damage various tissues, especially the brain, kidney, heart, nerves and so on. Diabetic disease is one of the main causes of visual impairment in diabetic patients. Early classification diagnosis is of great significance for the treatment and control of the disease. Deep learning methods can automatically extract the characteristics of retinopathy and classify them, so they become an important tool for the classification of diabetic retinopathy[1-3]. Firstly, the application of deep learning in the binary classification of diabetic retinopathy was summarized by introducing the commonly used data sets and evaluation indicators of diabetic retinopathy. Secondly, the application of different classical deep learning models in the classification of the severity of diabetic retinopathy was reviewed, with emphasis on the classification and diagnosis methods of convolutional neural network, and a comprehensive comparative analysis of different methods was made. Finally, the challenges facing this field are discussed and the future development direction is prospected.

Knowledge, attitude and practice of self-administered insulin by diabetes mellitus patients: A cross sectional study

Diabetes mellitus is a heterogeneous clinical syndrome secondary to defects in insulin secretion, action, or both. India is emerging as the world's diabetic capital. Inadequate awareness about the use of insulin is likely to influence its acceptance and adherence. To assess the knowledge, attitude, and practice (KAP) of self-administered insulin by patients of diabetes mellitus. It was a cross-sectional study conducted by the department of pharmacology at a tertiary care teaching hospital over a period of six months at the medicine outpatient department. A prevalidated questionnaire was used to assess the KAP of insulin use. Informed consent was obtained from the patients prior to giving them a questionnaire. Among the 151 responses, 58 were male and 93 were female. Among them, 66% knew about different types of insulin, and 32% knew about different insulin delivery devices. Around 40% of patients were not aware of HbA1c as a monitoring tool. Nearly 48% patients knew the complications of diabetes. Half of the patients were confident about the self-administration of insulin. About 54% patients took insulin for treatment. Among current insulin users, 75% injected insulin at the upper arm, 83% missed insulin doses, 74% had never used a glucometer, and 32% failed to rotate the site. Knowledge and attitude were good in the majority of patients, but practice regarding the use of insulin was poor. Skilled health care providers could educate diabetes mellitus patients on self-care management and insulin self-therapy and bridge this gap.

Medication Compliance in Type 2 Diabetes Patients: HbA1c and Lipid Profile at Aulia Jombang Clinic 2020

Diabetes Mellitus (DM) is a chronic metabolic disease characterized by high blood sugar levels due to insulin secretion or work defects. Poor treatment adherence leads to uncontrolled glycemic levels and complications. Therefore, ensuring patient adherence to therapy and reducing HbA1c and lipid profiles is essential. This research employs an observational, cross-sectional design, using non-probability purposive sampling to select 55 respondents via the Slovin formula. The study examines medication adherence as the independent variable, Hba1c levels, and lipid profile as the dependent variables. Data analysis involves SPSS, utilizing univariate and bivariate methods for ordinal and nominal scales. MMAS-8 questionnaire assesses the knowledge, while data comes from questionnaires and medical records of type 2 DM patients at Aulia Jombang Clinic. Study findings showed notable adherence to treatment, with 38 respondents (60.9%) complying and 17 (30.1%) not. Chi-square tests yielded significance, p values: HbA1c 0.012, LDL 0.035, total cholesterol 0.008, triacylglycerides 0.011, and HDL 0.002, based on MMAS-8 questionnaire data. In conclusion, the results indicate statistical significance (p-value < 0,05), so there is a positive correlation coefficient, indicating that higher levels of treatment adherence are associated with more optimal HbA1c control and lipid profiles.