Insulin Action Research Articles

A pilot study on screening for aminoacidurias using paper chromatography in subjects with type 2 diabetes and healthy subjects: Cross-sectional study

Diabetes is a heterogeneous chronic dysglycemic and dyslipidemic metabolic disorder principally characterized by persistent hyperglycemia resulting from defects in insulin action and/or insulin secretion. This pilot study is indented detect type of Aminoacidurias and number of amino acids detected in the urine and correlate number of amino acids detected with glycemic control marker glycated hemoglobin (HbA1c) in type 2 diabetic subjects and healthy controls. This present study included 40 subjects with type 2 diabetes and 40 age and gender matched healthy controls in the age group 25-60 years. Early morning first voided mid-stream urine sample of 5 mL was collected into the urine container and subjected to centrifugation to remove cell debris and the clear supernatant was used for preforming paper chromatography for detecting aminoacidurias. In type 2 diabetic subjects two or more than two amino acids up to seven are detected in the urine sample in comparison to healthy controls. The most commonly detected amino acids were valine (60%), glycine (45%), leucine (32.5%), alanine (22.5%) and histidine (25%). There was statistically significant strong correlation existed between HbA1c levels and number of amino acids detected in type 2 diabetic subjects (r=0.901). We found statistically significantly elevated levels of HbA1c and fasting plasma glucose levels in type 2 diabetic subjects compared to healthy controls.In type 2 diabetic subjects two or more than two amino acids were excreted in comparison to controls. It was observed that those patients with inadequate glycemic control had more number of amino acids detected in the urine evidenced by strongly correlation with HbA1c values. Detection of amino acids in the urine can be used as a non-invasive tool to predict glycemic control in type 2 diabetic patients. In addition to this, in type 2 diabetic subjects we get an information about the deficient amino acids and increased amino acids which can open the gateway for therapeutic modalities using amino acids.

A trend of osteocalcin in diabetes mellitus research: bibliometric and visualization analysis

BackgroundOsteocalcin has attracted attention for its potential role in diabetes management. However, there has been no bibliometric assessment of scientific progress in this field.MethodsWe analysed 1680 articles retrieved from the Web of Science Core Collection (WoSCC) between 1 January 1986 and 10 May 2024 using various online tools. ResultThese papers accumulated 42,714 citations,with an average of 25.43 citations per paper. Publication output increased sharply from 1991 onwards. The United States and China are at the forefront of this research area.DiscussionThe keywords were grouped into four clusters: ‘Differential and functional osteocalcin genes’, ‘Differential expression of osteocalcin genes in relation to diabetes mellitus’, ‘Role of osteocalcin in the assessment of osteoporosis and diabetes mellitus’, and ‘Indirect involvement of osteocalcin in metabolic processes’. Analysis using the VoS viewer suggests a shift in research focus towards the correlation between osteocalcin levels and diabetic complications, the clinical efficacy of therapeutic agents or vitamins in the treatment of osteoporosis in diabetic patients, and the mechanisms by which osteocalcin modulates insulin action. The proposed focus areas are “osteocalcin genes”, “insulin regulation and osteoporosis “, “different populations”, “diabetes-related complications” and “type 2 diabetes mellitus”,“effect of osteocalcin expression on insulin sensitivity as well as secretion”,“osteocalcin expression in different populations of diabetic patients and treatment-related studies”.

Muscle Cell Palmitate-Induced Insulin Resistance, JNK, IKK/NF-κB and STAT3 Activation are Attenuated by Carnosic and Rosmarinic Acid.

The worldwide epidemic of obesity has drastically worsened with the increase in more sedentary lifestyles and increased consumption of fatty foods. Increased blood free fatty acids (FFAs), often observed in obesity, leads to impaired insulin action, and promotes the development of insulin resistance and Type 2 diabetes mellitus (T2DM). JNK, IKK-NF-κB, and STAT3 are known to be involved in skeletal muscle insulin resistance. We reported previously that carnosic acid (CA) and rosmarinic acid (RA), attenuated the palmitate-induced skeletal muscle insulin resistance, an effect that was associated with increased AMPK activation and reduced mTOR-p70S6K signaling. In the present study, we examined the effects of CA and RA on JNK, IKK-NF-κB, and STAT3. Exposure of cells to palmitate increased the phosphorylation/activation of JNK, IKKα/β, IκBα, NF-κBp65, and STAT3. Importantly, CA and RA attenuated the deleterious effects of palmitate. Our data indicate that CA and RA have the potential to counteract the palmitate-induced skeletal muscle cell insulin resistance by modulating JNK, IKK-NF-κB, and STAT3 signaling.

Antidiabetic phytochemicals: an overview of medicinal plants and their bioactive compounds in diabetes mellitus treatment.

Diabetes mellitus (DM) is a group of metabolic disorders characterized by hyperglycemia due to insufficient insulin secretion or action. Contributing factors include genetic predisposition, obesity, family history, inactivity, and environmental risks. Type 2 diabetes mellitus (T2DM), the most common form, involves impaired insulin secretion by pancreatic β-cells, leading to insulin resistance. By 2045, it is projected that India and China will have approximately 134.3 and 110.8 million diabetic individuals, respectively. Although synthetic drugs are effective in managing DM, they often come with side effects. Consequently, plant-based phytochemicals with antidiabetic properties are gaining attention. Research indicates that around 115 medicinal plants (MPs) have antidiabetic effects, particularly those from the Fabaceae, Liliaceae, and Lamiaceae families. Bioactive compounds like alkaloids, triterpenoids, flavonoids, and phenolics are known to combat DM. Traditional medicinal systems, particularly in developing countries, offer effective DM management. This review highlights the importance of MPs and their bioactive compounds in treating diabetes and underscores the need for further research to commercialize plant-based antidiabetic drugs.

Exercise promotes peripheral glycolysis in skeletal muscle through miR-204 induction via the HIF-1α pathway

The mechanisms underlying exercise-induced insulin sensitization are of great interest, as exercise is a clinically critical intervention for diabetic patients. Some microRNAs (miRs) are secreted from skeletal muscle after exercise where they regulate insulin sensitivity, and have potential as diagnostic markers in diabetic patients. miR-204 is well-known for its involvement in development, cancer, and metabolism; however, its role in exercise-induced glycemic control remains unclear. In the present study, endurance exercise in mice increased miR-204 expression levels in skeletal muscle. In a chronic exercise model, miR-204 expression levels were elevated along with glycolytic enzymes in skeletal muscle. When muscular hypoxia was induced after exercise, miR-204 expression also increased with the upregulation of hypoxia-inducible factor 1-alpha (HIF-1α). Furthermore, HIF-1α overexpression led to increased miR-204 expression. Treatment with a miR-204 mimic in C2C12 cells significantly enhanced the glycolysis rate and the mRNA expression of glycolytic enzymes. Notably, intravenous administration of miR-204 in mice increased the glucose clearance rate following refeeding. miR-204 initially elevated blood glucose levels at an early stage of refeeding but later promoted blood glucose reduction as refeeding continued. Additionally, glycolytic enzymes were upregulated in the skeletal muscles of miR-204-injected mice. These findings suggest a novel physiological role for miR-204 in promoting skeletal muscle glycolysis, particularly in situations where insulin action is limited.

Impact of TCF7L2 rs7903146 on clinical presentation and risk of complications in patients with type 2 diabetes.

TCF7L2 rs7903146 is the most impactful single genetic risk variant for type 2 diabetes. However, its role on disease progression, complications and mortality among people with type 2 diabetes at diagnosis remains unclear. We assessed the per allele impact of the rs7903146 T-allele on clinical characteristics and complication risk in 9231 individuals with type 2 diabetes at diagnosis and over a 10-year follow-up period. Log-binomial and robust Poisson regression analyses were used to estimate prevalence ratios for clinical characteristics and macro- and microvascular complications at diabetes onset, while Cox regression was applied to estimate the risk of complications post-diagnosis. Analyses were adjusted for sex, calendar year at birth, age at enrollment and diabetes duration. The per T-allele impact was associated with 0.6 kg/m2 (95% CI: 0.4, 0.8) lower BMI, 1.4 cm (95% CI: 1.0, 1.8) smaller waist circumference, 5.6% (95% CI: 4.2, 7.0) lower insulin secretion and 5.0% (95% CI: 3.3, 6.7) higher insulin sensitivity. Over 10 years, the per T-allele impact was associated with lower risks for major adverse cardiovascular events (0.87 [95% CI 0.79, 0.95]), myocardial infarction (0.82 [95% CI: 0.72, 0.93]) and heart failure (0.85 [95% CI 0.73, 1.00]), with no significant impact on microvascular complications. The TCF7L2 variant is associated with less obesity, lower insulin secretion and higher insulin action at diabetes onset, and decreased risk of cardiovascular events following type 2 diabetes onset.

Abnormal glucagon secretion contributes to a longitudinal decline in glucose tolerance.

Defects in insulin secretion and action contribute to the progression of prediabetes to diabetes. However, the contribution of α-cell dysfunction to this process has been unclear. Understand the relative contributions of α-cell and β-cell dysfunction to declining glucose tolerance. Longitudinal, community-based observational study. Clinical Research Unit at an Academic Medical Center. We studied 96 subjects without diabetes (55 ± 1 years; BMI 27.7 ± 0.4 Kg/M2) on 2 occasions, 3 years apart using an oral 75g glucose challenge. Indices for insulin secretion and action were estimated using the oral minimal model. Glucagon secretion rate (GSR) was estimated by deconvolution from peripheral glucagon concentrations. This was an observational study. Glucose tolerance status (categorical variable) and then symmetrical percent change in peak and 120-minute glucose (post-OGTT) concentrations (continuous variables). 32 subjects progressed from normal to Impaired Glucose Tolerance (IGT) or from IGT to type 2 diabetes. Disposition Index (DI) declined in the progressors (568±98 vs. 403±65 10-4 dl/kg/min per μU/ml, baseline vs. 3-years p=0.04). α-cell suppression by glucose (δGSR/δglucose) did not change in the non-progressors (1.5±0.1 vs. 1.3±0.1 nmol/min/L, p=0.37) but decreased (1.0±0.2 vs. 0.8±0.2 nmol/min/L, p<0.01) in those who progressed. Analysis of the entire cohort showed that DI and δGSR/δglucose were independently and inversely correlated with an increase in glycemic excursion. These data show that α-cell dysfunction accompanies a decline in β-cell function as IGT or overt type 2 diabetes develops.

GLP-1 enhances β-cell response to protein ingestion and bariatric surgery amplifies it.

The glycemic-independent actions of glucagon-like peptide-1 (GLP-1) in the prandial state in humans are unknown. We examined the contribution of GLP-1 to β-cell secretory response (primary endpoint) and glucose metabolism during protein ingestion under basal glycemia, as well as whether these responses are affected by rerouted gut after gastric bypass (GB) or sleeve gastrectomy (SG). Insulin secretion rate (ISR) and glucose fluxes during a 50-g oral protein load were compared among 10 nondiabetic individuals with GB, 9 with SG, and 7 non-operated controls (CN), with and without intravenous infusion of exendin(9-39) (Ex-9), a GLP-1 receptor (GLP-1R) antagonist. Blocking GLP-1R increased glucose before and after protein ingestion and decreased β-cell sensitivity to glucose in the first 30 min of protein ingestion in all three groups (p < 0.05). Reduction in the premeal ISR by Ex-9 infusion was only observed in CN, whereas diminished prandial ISR3h by GLP-1R blockade was only observed in GB and SG (p < 0.05 for interaction). GLP-1R blockade enhanced post-protein insulin action in GB and SG, but not in CN, and exaggerated endogenous glucose production only GB (p < 0.05 for interaction). These findings are consistent with both pancreatic and extra-pancreatic roles for GLP-1 during protein ingestion in humans that are exaggerated by bariatric surgery.

New C-linked diarylheptanoid dimers as potential α-glucosidase inhibitors evidenced by biological, spectral and theoretical approaches.

Diabetes mellitus (DM) is a chronic metabolic disorder characterized by elevated blood glucose levels, generally due to defects of insulin action or secretion. Inhibition of α-glucosidase, an enzyme responsible for carbohydrate degradation, is a promising strategy for managing postprandial hyperglycemia in diabetic patients. In this study, two new C-linked diarylheptanoid dimers, kaemgalanganols A (1) and B (2), were isolated from K. galanga, which showed obvious inhibitory activity on α-glucosidase but weak activity on protein tyrosine phosphatase 1B (PTP1B). Kaemgalanganol B had an IC50 value of 35.1μM against α-glucosidase, obviously more potent than kaemgalanganol A (IC50=78.5μM) and acarbose (IC50=363.0μM). Enzyme kinetic study indicated that 2 was a reversible mixed-type inhibitor of α-glucosidase via non-competitive and anti-competitive inhibition modes. Fluorescence quenching and UV-visible spectroscopic study revealed that fluorescence quenching mechanism of 2 on α-glucosidase is a combination of dynamic quenching and static quenching, accompanied by non-radiative energy transfer. Compound 2 formed complex with α-glucosidase closer to the Tyr residue, and induced changes in both the microenvironment and peptide backbone. Surface hydrophobicity and CD spectra measurement indicated that 2 affected the function of α-glucosidase by decreasing the surface hydrophobicity of α-glucosidase as well as altering the secondary structure instead of the overall three-dimensional framework, which is consistent with the results of fluorescence experiment. Molecular docking manifested that compound 2 had a strong binding affinity (-7.27kcal/mol) with α-glucosidase, higher than 1 (-9.82kcal/mol) and acarbose (-4.48kcal/mol), consistent with the enzyme inhibitory assay. Besides hydrogen bonds, electrostatic interactions and hydrophobic interactions played important roles in the binding of 2 with α-glucosidase. This study disclosed the inhibitory activity and mechanism of 2 against α-glucosidase, which provides a theoretical basis for the development of new antidiabetic drugs form K. galanga.

Distinct dynamic regulation of pectoralis muscle metabolomics by insulin and the promotion of glucose-lipid metabolism with extended duration

Birds' glycolipid metabolism has garnered considerable attention due to their fasting blood glucose levels being nearly twice those of mammals. While skeletal muscle is the primary insulin-sensitive tissue in mammals, the effects of insulin on chicken skeletal muscle remain unclear. In this study, the insulin-responsive metabolites were identified in broiler's pectoralis muscle (after 16 h of fasting) using widely targeted metabolomics. Glycolipid concentrations were measured using kits, and the expression of key genes involved in glucose metabolism was assessed via quantitative real-time PCR (qRT-PCR). The insulin tolerance test, performed by injecting 5 IU/kg body weight of insulin, demonstrated a rapid drop in blood glucose levels from 0 to 15 min, with a consistent reduction observed at 120 min (P < 0.01). Insulin did not alter glucose and glycogen content in chicken pectoralis; however, low-density lipoprotein (LDL, P < 0.05) levels were upregulated in the early phase (15 min). With an extended insulin duration (120 min), pectoralis glucose content increased (P < 0.05), accompanied by a reduction in TG levels (P < 0.05). Metabolomic analysis revealed that insulin promotes the downregulation of 63 out of 71 metabolites at 15 min and the upregulation of 101 out of 134 metabolites at 120 min, mainly associated with lysine degradation and thyroid hormone signaling pathways, respectively. 7 metabolites were dynamically modulated in the same manner over time (2 up-up and 5 down-down). Early insulin inhibited glycolysis, evidenced by the reduction in phosphoenolpyruvate levels and hexokinase 2 (HK2) expression; however, insulin promoted glucose uptake through the activation of glucose transporter 4 (GLUT4) and enhanced glycolysis, accompanied by elevated fatty acid metabolism at the later phase. In conclusion, insulin dynamically regulates the metabolomics of the pectoralis muscle over time. Initially, chicken muscle tissues downregulate metabolic activities to accommodate the new signaling state, followed by significant upregulation to meet heightened metabolic demands. Extended insulin monitoring promotes glucose uptake and glycolysis, alongside enhanced fatty acid metabolism. This research provides insights into the potential mechanisms of insulin action in chicken muscles.

Analysis of Exosomal miRNA and Hepatic mRNA Expression in the Dysregulation of Insulin Action in Perimenopausal Mice

Analysis of Exosomal miRNA and Hepatic mRNA Expression in the Dysregulation of Insulin Action in Perimenopausal Mice

Evaluating of Anti-Diabetic Potential and Beneficial Effect of Nutraceutical Powder in Management of Various Diabetic Complication

Diabetes mellitus is a chronic disorder that generates raised more blood glucose levels due to insufficient insulin production or activity. This illness's metabolic imbalance raises the likelihood of long-term problems in blood vessels, resulting in frequent hospitalization and increased risk of cardiovascular disease. Providing appropriate treatment to diabetic patients is vital to avert complications. Female Wistar rats were divided into different groups (n = 6). Eight groups each one induced alloxan to type1 diabetes and treated with different doses of nutraceutical powder. 24 h after the last dose, animals were subjected to behavioural, biochemical, and histopathological evaluations. The data were analysed by one-way ANOVA. In in-vitro model of alpha amylase inhibition assay the absorbance of sample increased as the concentration of nutraceutical powder will increase. In alloxan induced in vivo diabetic model in Wistar rats the body weight, the water intake observed the increasing in disease control as comparing to normal, standard, Test drug group1 lower dose(200mg/kg) and Test drug group 2(500mg/kg), the food intake observed the decreasing in disease control as comparing to normal, standard, Test drug group1 lower dose(200mg/kg) and Test drug group 2(500mg/kg).After 45 days of study, all biochemical parameters the blood, LDL, insulin and creatinine level observed the increasing in disease control group with comparing to normal control, standard control and tests groups. The study will conclude our formulation has potential for managing diabetes by stimulating the regeneration of pancreatic β-cells and further research is needed to understand the active constituents and mechanism of action.

Assessment of the relationship between serum uric acid levels and oxidative stress markers in patients with uncomplicated type 2 diabetes mellitus

Objective: Type 2 Diabetes Mellitus is a worldwide health issue characterized by hyperglycemia due to defects in insulin secretion, insulin action, or both, and is associated with significant negative health outcomes. Oxidative stress plays a crucial role in the onset, progression, and complications of this disorder. Elevated serum uric acid level is an independent predictor of vascular complications in diabetic patients, and hyperuricemia may contribute to oxidative stress. The objective of this study is to examine the correlation between increased serum uric acid levels and the markers of oxidative stress, including ischemia-modified albumin (IMA), total oxidant status (TOC), and total antioxidant capacity (TAC), in type 2 diabetic patients who don’t have vascular complications. Materials and Methods: A total of 73 individuals were enrolled in the study including 20 type 2 diabetic patients with high serum uric acid levels (&gt; 6.5 mg/dl), 21 type 2 diabetic patients with normal serum uric acid levels (&lt; 6.5 mg/dl), and 32 healthy individuals. Ischemia-modified albumin, total oxidant status, and total antioxidant status levels were compared between patient groups and the control group Results: As a result of this study, there was no significant association between serum uric acid levels and ischemia-modified albumin, total oxidant status, and total antioxidant status levels in type 2 diabetic patients. Conclusions: This study concluded that high serum uric acid levels do not directly affect oxidative stress in type 2 diabetic patients without vascular complications.

The Effect of Osteocalcin in Middle-Age Women With and Without Type2 Diabetes Mellitus

Background: Diabetes mellitus is a chronic disease that affects people of all ages. It's caused by deficiencies in insulin action and secretion, leading to long-term hyperglycemia. This can harm key organs such as the kidneys, heart, eyes, nerves, and blood vessels. Managing diabetes requires significant lifestyle changes and can impact both the patient and their family. Small and bone-specific, osteocalcin (OCN) is a non-collagen protein that is mostly present in bone. It is a sensitive marker of bone formation and primarily attaches to the extracellular matrix of bone after being carboxylated. Small amounts of OCN are also released into the bloodstream, where it aids in glucose and fat metabolism. Objective: Our study aimed to examine the effect of Osteocalcin, Parathyroid hormone, Estrogen and HbA1c on middle-aged women who had type 2 diabetes compared to those who did not. Patients and Methods: The study involved 90 middle-aged women, including 60 with type 2 diabetes, and 30 healthy women. The Sandwich enzyme-linked immunosorbent assay was used to measure OCN, PTH, and E2 hormone levels in women with and without type 2 diabetes. HbA1c levels were measured using the Cobos system. The statistical analysis was performed using SPSS software. Results: In T2DM women, serum OCN, PTH, E2, and HbA1c levels were compared with non-diabetic women. T2DM women had significantly lower levels of serum OCN and PTH, and significantly higher levels of HbA1c than healthy women. Serum E2 levels were also significantly lower in T2DM women. OCN had a positive correlation with HbA1c and negative correlations with PTH and E2. Conclusion: Significant change was detected in this study in the level of OCN, PTH and E2 between patients and controls. Investigations of serum OCN can be participated in the future as predictive marker for osteoporosis in diabetic women. Keywords: Osteocalcin, parathyroid hormone, estrogen, Type2 diabetes mellitus.

Beta-cell, but not autonomic nervous system, function is related to MAFLD in early stages of glucose intolerance

IntroductionPrevious studies have suggested an association between beta-cell and autonomic function and metabolic-associated fatty liver disease (MAFLD). We explored the association between controlled attenuated parameter (CAP) and insulin secretion and...

Glucose regulation and association with Vitamin D and parathyroid hormone – differences across Middle Eastern and Caucasian ethnicities

BackgroundMiddle Eastern (ME) immigrants to Europe have a heavy burden of metabolic disorders including a higher prevalence of insulin resistance, T2D and obesity as compared to native-born Europeans. Vitamin D insufficiency and deficiency are prevalent conditions in people originating from the ME.AimsTo study the differences in the levels of 25(OH)D and parathyroid hormone (PTH) across ME and European ethnicity, and the effect of 25(OH)D and PTH on insulin action and secretion.MethodsVitamin D and PTH levels were assessed in a population-based cohort of 918 participants (449 Swedes and 469 Iraqis) aged 30–75 years. The differences between the groups in the adjusted levels of Vitamin D and PTH were studied using multiple regression analysis. Differences in insulin action and secretion, in relation to risk markers including Vitamin D and PTH, were assessed using multiple regression analysis.ResultsVitamin D and PTH adjusted levels differed significantly between the groups; 92% of the Iraqi-born versus 45% of the Swedish-born individuals had Vitamin D levels below 50 nmol/L. The mean levels of PTH (SD) were higher in Iraqi-born compared to native Swedish-born (5.1 (2.3) vs. 3.8 (1.6) pmol/L, p = < 0.001). Insulin sensitivity was lower in Iraqi-born (79.16 vs. 98.97, β -0.085, 95% CI −.163 to −.007) but after adjustment for the confounding effect of Vitamin D, the differences in insulin action observed between the groups were no longer significant.ConclusionThe ethnic differences in insulin action could be explained by differences in the levels of Vitamin D.

Phycocyanin/Hyaluronic Acid Microneedle Patches Loaded with Celastrol Nanoparticles for Synergistic Treatment of Diabetic Nephropathy.

Although multifunctional drug delivery systems have shown significant potential in the treatment of diabetic nephropathy (DN), developing an efficient synergistic drug delivery strategy remains a major challenge. The purpose of this paper is to develop a nanoparticle-loaded microneedle (MN) patch transdermal drug delivery system aimed at achieving blood glucose control and reactive oxygen species (ROS) scavenging for the synergistic treatment of DN. MNs are composed of hyaluronic acid and phycocyanin (PC), both exhibiting excellent biocompatibility and degradation properties. Subsequently, insulin and celastrol (CEL)-based nanoparticles were incorporated into the MN to create the transdermal drug delivery platform (MN-IN&NPs). MN-IN&NPs can penetrate through the stratum corneum of skin and reach the dermis layer. Accompanied by the dissolution of MN, PC, insulin, and CEL-based NPs are continuously released. PC possesses anti-inflammatory and antioxidant properties that enable it to scavenge excessive ROS, thereby exerting synergistic effects alongside CEL nanoparticles. Furthermore, MN-IN&NPs significantly enhance drug transdermal delivery efficiency, while prolonging insulin's action duration. Therefore, MN-IN&NPs effectively integrate blood glucose control with ROS scavenging functions, presenting a promising therapeutic strategy for DN.

Why do they use bhat chew sticks? An experiment to demonstrate the antihyperglycemic activity of Clerodendrum infortunatum Linn.

Introduction: The rise in blood glucose than the recommended level is called hyperglycemia, mainly caused by diabetes mellitus (DM). DM is in turn a consequence of decreased insulin secretion or action or both. This experiment is intended to evaluate the effect of Clerodendrum infortunatum Linn. (bhat) chew sticks in controlling diabetes in humans. Method: The fasting blood sugar was measured twice with the help of a glucometer. First, all participants were requested to measure their blood sugar on an empty stomach in the morning without using a bhat chew stick. The next morning, their fasting plasma sugar was again accessed after the use of the bhat chew sticks as a toothbrush. The fall in blood sugar value was recorded and the efficiency of the stimulus was tested using student t-test at α level of significance and n-1 degree of freedom. Result: A total of 27 individuals participated in the study and all responded to the stimulus. A fall in blood glucose was observed between 3-59 mg/dL and the response was not found to be significant at 0.05 level of significance. Conclusion: Rural people use chew sticks as toothbrushes and prefer C. infortunatum twigs to control diabetes. The present experiment shows that bhat lowers the blood sugar level in both diabetic and non-diabetic individuals. However, chronic impacts should also be monitored by conducting large-scale studies on humans to establish proper dosage, indications, and side effects of C. infortunatum. Keywords: Clerodendrum infortunatum, diabetes, hyperglycemia, random blood sugar, chew stick.

Correlation between Hypertension and the Severity of Diabetic Retinopathy in Diabetes Mellitus Patients at Waled Regional General Hospital: A Cross-Sectional Study

Background: Diabetes mellitus is a metabolic disorder characterized by elevated blood sugar levels and resulting from deviations in either insulin secretion, insulin action, or both. Prolonged hyperglycemia can lead to various complications, including diabetic retinopathy. The main risk factors for developing diabetic retinopathy are uncontrolled diabetes mellitus, hypertension, and dyslipidemia. Aims: To determine the correlation between hypertension and the severity of diabetic retinopathy in diabetes mellitus patients at Waled Regional General Hospital, Cirebon, from 2020 to 2023. Methods: This study used an analytical observational method with a cross-sectional design. We collected data from the medical records of patients with diabetic retinopathy at Waled Regional General Hospital from 2020 to 2023. This study employed total sampling as its sampling technique. We performed univariate analysis to determine the frequency distribution of the samples and bivariate analysis using the Spearman correlation test. Results: Out of 50 diabetic retinopathy patients, the majority suffered from proliferative diabetic retinopathy (PDR), with 22 (44%) patients. The most common blood pressure level among the patients was grade 2 hypertension, with 19 (38%) patients. The bivariate analysis in this study showed a P-value of 0.091 and an r-value of 0.242. Conclusion: There is no significant correlation between hypertension and the severity of diabetic retinopathy in diabetes mellitus patients at Waled Regional General Hospital from 2020 to 2023, with a positive correlation direction (p-value: 0.091 and r-value: 0.242). Received: 25 September 2024 | Reviewed: 16 October 2024 | Revised: 30 November 2024 | Accepted: 12 December 2024.

Insulin activates parasympathetic hepatic-related neurons of the paraventricular nucleus of the hypothalamus through mTOR signaling.

Integration of autonomic and metabolic regulation, including hepatic function, is a critical role played by the brain's hypothalamic region. Specifically, the paraventricular nucleus of the hypothalamus (PVN) regulates autonomic functions related to metabolism, such as hepatic glucose production. Although insulin can act directly on hepatic tissue to inhibit hepatic glucose production, recent evidence implicates central actions of insulin within PVN also regulates glucose metabolism. However, specific central circuits responsible for insulin signaling with relation to hepatic regulation are poorly understood. As a heterogenous nucleus essential to controlling parasympathetic motor output with notable expression of insulin receptors, PVN is an appealing target for insulin-dependent modulation of parasympathetic activity. Here, we tested the hypothesis that insulin activates hepatic-related PVN (PVNhepatic) neurons through a parasympathetic pathway. Using transsynaptic retrograde tracing, labeling within PVN was first identified 24 h after its expression in DMV and 72 h after hepatic injection. Critically, nearly all labeling in medial PVN was abolished after a left vagotomy, indicating that PVNhepatic neurons in this region are part of a central circuit innervating parasympathetic motor neurons. Insulin also significantly increased firing frequency of PVNhepatic neurons in this subregion. Mechanistically, rapamycin pretreatment inhibited insulin-dependent activation of PVNhepatic neurons. Therefore, central insulin signaling can activate a subset of PVNhepatic neurons which are part of a unique parasympathetic network in control of hepatic function. Taken together, PVNhepatic neurons related to parasympathetic output regulation could serve as a key central network in insulin's ability to control hepatic functions.