Hypoglycemic Effect Research Articles

Teleconsultation on patients with type 2 diabetes in the Brazilian public health system: a randomised, pragmatic, open-label, phase 2, non-inferiority trial (TELECONSULTA diabetes trial)

This study addresses the rising burden of type 2 diabetes mellitus, and explores the potential of teleconsultation, as an alternative for diabetes management. The primary objective was to test the hypothesis that teleconsultation is non-inferior to face-to-face consultation in terms of glycaemic control measured as glycated haemoglobin (HbA1c) (non-inferiority margin for the upper confidence interval for the difference between groups of 0,5% in HbA1c) for type 2 diabetes mellitus patients referred from Primary Healthcare to Specialized Care within the SUS. TELECONSULTA, is a randomized, pragmatic, phase 2, single-centre, open-label, non-inferiority trial conducted in Joinville, Brazil. A total of 278 participants diagnosed with type 2 diabetes were randomized through mandatory teleconsulting services from primary care health units. The randomization was 1:1 to teleconsultation or face to face consultation. The study was registered at the Brazilian Clinical Trial Register-REBEC, under the code RBR-8gpgyd. Study status is "Completed". This study included 278 participants in the intention-to-treat (ITT) analysis. The median age was 61 (54-68) years, 167 (60%) were women. The between-groups comparative average reduction in HbA1c was-0.6% (90% CI-1.0;-0.1) at 3-months and-0.5% (90% CI-0.9; 0.0) at 6-months in Modified Intention-to-Treat (mITT) population with imputed data, showing the non-inferiority of teleconsultation. Results with no missing data imputation and in the per protocol population were similar. The frequency of hypoglycaemia and other adverse events was well balanced between groups. The results underscore the transformative potential of telemedicine in addressing the complexities of diabetes management within the framework of a universal healthcare system, contributing with valuable insights for healthcare policymakers and practitioners seeking innovative solutions to tackle the growing diabetes epidemic. This study was funded by the Brazilian Ministry of Health, through the Unified Health System-Institutional Development Support Program (PROADI-SUS).

Evaluation of anti-diabetic effects of Glimepiride/metformin cocrystal

Emerging data suggest that cocrystal of two compounds may have a different pharmacological effect from two compounds alone or their physical combination. Glimepiride (Gli) and metformin (Met) are two types of anti-diabetic drugs. Previously we generated the glimepiride/metformin cocrystal (GM). In this study, we evaluated the anti-diabetic effects of GM and explored the underlying mechanisms. Our result showed that GM reduced the blood glucose and HbA1c levels in db/db mice, and low doses of GM can achieve the hypoglycemic effect as Gli or Met alone, and high dose of GM was better than Gli and Met alone in improving the pathological changes of liver. In vivo studies showed that GM activated AMPK and STAT3 signaling, downregulated TXNIP expression and upregulated MaFA expression. Moreover, GM promoted the secretion of insulin in pancreas of db/db mice and in high glucose-treated INS-1 and MIN-6 cells. Together, GM possesses slightly better anti-diabetic effects than Met or Gli alone in db/db mice, and the mechanism of GM protecting β-cell dysfunction induced by glucotoxicity may be associated with activation of the AMPK/TXNIP/MaFA pathway.

Oral administration of herbal oligonucleotide drug JGL-sRNA-h7 ameliorates hyperglycemia in db/db mice and beagle dogs.

Type 2 diabetes mellitus is a prevalent metabolic disease, posing a considerable threat to public health. Oligonucleotide drugs have proven to be a promising field of therapy for the diseases. In this study, we reported that a herbal small RNA (sRNA), JGL-sRNA-h7 (B34735529, F1439.L002444.A11), could exhibit potent hypoglycemic effects by targeting glucose-6-phosphatase. Oral administration of sphingosine (d18:1)-JGL-sRNA-h7 bencaosomes ameliorated hyperglycemia and diabetic kidney injury better than metformin in db/db mice. Furthermore, glucose tolerance was also improved in sphingosine (d18:1)-JGL-sRNA-h7 bencaosomes-treated beagle dogs. Our study indicates that JGL-sRNA-h7 could be a promising hypoglycemic oligonucleotide drug.

Andrographis paniculata improves glucose regulation by enhancing insulin sensitivity and upregulating GLUT 4 expression in Wistar rats.

Although the hypoglycaemic effect of Andrographis paniculata (Burm.f.) Nees [Acanthaceae] has been documented, reports on its effect in an apparently healthy state are limited. This study investigated whether or not A. paniculata exerts hypoglycaemic effect in a non-diabetic state. It also explored the impact of A. paniculata on glycolytic enzymes and GLUT 4 protein expression, as a possible mode of action. Twenty male Wistar rats were randomly assigned into two groups (n = 10 rats/group). The control rats were vehicle-treated (0.5 ml of distilled water), while the A. paniculata-treated rats had 500 mg/kg of A. paniculata per os once daily for 35 days. A. paniculata treatment led to improved insulin sensitivity evidenced by increased HOMA-β (88.08 ± 2.13 vs. 120.80 ± 1.52, p < 0.0001), HOMA-S (283.60 ± 8.82 vs. 300.50 ± 9.30, p = 0.0189), and reduced TyG index (4.22 ± 0.04 vs. 3.95 ± 0.07, p < 0.0002) and HOMA-IR (0.32 ± 0.01 vs. 0.25 ± 0.01, p < 0.0001) when compared with the control. It also improved glucose regulation as depicted by reduced fasting blood glucose (3.77 ± 0.10 vs. 3.24 ± 0.11, p < 0.0001) and glycated hemoglobin (HbA1c; 7.69 ± 1.15 vs. 5.95 ± 0.82, p = 0.0245), and atherogenic dyslipidaemia, including AIP (-0.12 ± 0.03 vs. -0.26 ± 0.03, p < 0.0001) and CRI-I (2.70 ± 0.29 vs. 1.84 ± 0.27, p < 0.0001). These findings were accompanied by enhanced hepatic and muscular redox state, increased activities of glycolytic enzymes, upregulated GLUT 4 (0.80 ± 0.27 vs. 6.20 ± 0.84, p < 0.0001), and increased circulating nitric oxide (5.45 ± 0.24 vs. 6.79 ± 0.33, p = 0.0002). A. paniculata exerts positive effect on glucose metabolism and utilization by improving insulin sensitivity and upregulating the activities of glycolytic enzymes and GLUT 4 protein expression. This implies that A. paniculata may be beneficial in preventing insulin resistance and incident diabetes. Nonetheless, it should be used with caution to prevent hypoglycaemia in a non-diabetic state.

Effectiveness and Safety of GLP-1 Receptor Agonists in Patients with Type 1 Diabetes.

Background: GLP-1 receptor agonists (GLP-1RA) are used in the management of type II diabetes mellitus or obesity, although its role in patients with type I diabetes mellitus (T1DM) has been debated. This study aimed to investigate the efficacy and safety of GLP-1RA in patients with T1DM using real-world data. Methods: This multicenter, retrospective study was conducted at three tertiary medical centers in Riyadh, Saudi Arabia. The study followed up patients (>16 years old) with T1DM treated with insulin followed by GLP-1RA add-on therapy. The efficacy outcomes included changes in HbA1c, body weight, and insulin requirements from baseline to each follow-up visit. The main safety outcomes assessed included hypoglycemic events and gastrointestinal (GI) adverse events. Results: The study included 144 patients with a mean age of 33.0 ± 10.1 years. Semaglutide was the most used GLP-1RA (63.9%) followed by liraglutide (34.0%). From baseline to 3-month follow-up, HbA1c (mean difference (MD) = -0.8%; p = 0.0053), weight (MD = -2.4 kg; p = 0.0253), and daily basal insulin dose (MD = -2.1 units; p = 0.0349) were significantly reduced. Likewise, HbA1c (MD = -0.5%; p = 0.0004), weight (MD = -3.6 kg; p < 0.0001), and daily basal insulin (MD = -2.4 units; p = 0.0282) were significantly reduced at the 4-6-month follow-up. The significant reductions in HbA1c, weight, and daily basal insulin levels were consistent for up to 18-month follow-up. Only one patient had a major hypoglycemic event, whereas 8.3% of the patients had GI adverse events. Conclusions: Overall, significant improvements in glycemic control, weight loss, and insulin requirements were observed with the use of GLP-1RA in patients with T1DM, with a limited number of GI adverse events.

Advances in Research on the Anticancer Properties and Mechanisms of Metformin in Lung Cancer.

Lung cancer is a leading cause of death globally with high mortality and morbidity. Patients are often diagnosed at an advanced stage. Metformin has become a primary medication used in the clinical management of type 2 diabetes mellitus (T2DM) due to its relative safety, low cost, and effectiveness, mainly exerting its hypoglycemic effect by inhibiting hepatic gluconeogenesis and insulin resistance. Research data indicate that metformin extends the distant metastasis-free survival (DMFS) and progression-free survival (PFS) of diabetic patients with lung cancer, improving overall survival rates. Metformin lowers the risk of tumour development through various mechanisms, including the adenosine 5'-monophosphate-activated protein kinase/liver kinase B1/mechanistic target of rapamycin (AMPK/LKB1/mTOR) pathway, insulin-like growth factor-1 receptor pathway, apoptosis, and autophagy. However, research findings are not entirely consistent. This article reviews the research progress of metformin in terms of lung cancer treatment within the past few years, aiming to provide a more comprehensive understanding of how metformin exerts its anti-cancer impact and how it can be clinically applied, as well as provide new insights for lung cancer treatment.

Floral Elegance Meets Medicinal Marvels: Traditional Uses, Phytochemistry, and Pharmacology of the Genus Lagerstroemia L.

The genus Lagerstroemia L. (Lythraceae), known for its exquisite flowers and prolonged flowering period, is commonly employed in traditional medicinal systems across Asian countries, where it has always been consumed as tea or employed to address ailments such as diabetes, urinary disorders, coughs, fevers, inflammation, pain, and anesthesia. Its diverse uses may be attributed to its rich active ingredients. Currently, at least 364 biological compounds have been identified from Lagerstroemia extracts, encompassing various types such as terpenes, flavonoids, phenolic acids, alkaloids, and phenylpropanoids. Extensive in vitro and in vivo experiments have examined the pharmacological activities of different extracts, revealing their potential in various domains, including but not limited to antidiabetic, anti-obesity, antitumor, antimicrobial, antioxidant, anti-inflammatory, analgesic, and hepatoprotective effects. Additionally, 20 core components have been proven to be associated with antidiabetic and hypoglycemic effects of Lagerstroemia. Overall, Lagerstroemia exhibit substantial medicinal potential, and the alignment between its traditional applications and contemporary pharmacological findings present promising opportunities for further investigation, particularly in food and health products, drug development, herbal teas, and cosmetics. However, evidence-based pharmacological research has largely been confined to in vitro screening and animal model, lacking clinical trials and bioactive compound isolations. Consequently, future endeavors should adopt a more holistic approach.

The Potential Role of Beetroot Juice in Hyperglycemia Management: A Review of Mechanisms and Clinical Outcomes

Hyperglycemia, characterized by elevated blood glucose levels, is a significant health concern that affects millions of individuals worldwide. It has been associated with long-term complications affecting the cardiovascular, renal, and nervous systems. Beetroot juice (BRJ), rich in nitrates, betalains, and antioxidants, has gained attention for its potential role in mitigating hyperglycemia and improving insulin sensitivity. This review evaluates the available scientific evidence on the hypoglycemic effects of beetroot juice, explores its proposed mechanisms of action, and discusses its potential as a complementary therapy for diabetes management. By analyzing studies, we found that beetroot juice may help manage hyperglycemia by enhancing insulin sensitivity through its nitrate content, which converts to nitric oxide. Clinical evidence indicates it may lower fasting blood glucose and improve glycated hemoglobin A1c (HbA1c) levels, though results vary. While beetroot juice shows promise as a supplementary treatment for hyperglycemia, more research is needed to determine the optimal dosage, long-term effects, and interactions with other diabetes management strategies.

Extraction, in vitro hypoglycaemic activity and active ingredient analysis of polyphenols from walnut green husk

A variety of polyphenols in walnut green husk have shown physiological benefits, but their primary hypoglycemic active ingredients remain unclear. We report the extraction of walnut green husk polyphenols (WGHP) and their hypoglycemic effects in vitro. WGHP was extracted using ultrasound-assisted ethanol extraction, with optimization via response surface methodology resulting in 88.0 ± 0.1 % purity after D101 macroporous resin purification. WGHP effectively inhibited α-glucosidase and α-amylase, with IC50 values of 3.42 μg/mL and 2.56 mg/mL, respectively. It also increased glycogen synthesis in insulin-resistant HepG2 cells and enhanced glucose consumption in 3T3-L1 and insulin-resistant HepG2 cells. Screening six α-glucosidase ligands from WGHP using affinity ultrafiltration and UPLC-MS/MS, combined with molecular docking, identified hydrogen bonds and binding energies between the ligands and the enzyme. These results highlight the hypoglycemic potential of walnut green husk polyphenols and provide a basis for future therapeutic research.

Phytochemical Riches, Bioactivities, and Clinical Potential of Prinsepia utilis Royle: A Comprehensive Review

Prinsepia utilis Royle, widely recognized in Chinese and Indian traditional medicine, has attracted significant interest in the realms of phytochemistry and bioactivity research. This deciduous shrub from the Rosaceae family thrives in the Himalayan region at altitudes between 1000 and 3000 meters. The current paper aims to consolidate existing knowledge on P. utilis, providing an updated database of its phytochemical constituents and related bioactivities. Investigations have revealed a wealth of secondary metabolites, including alkaloids, flavonoids, phenolics, and terpenoids. Research has shown that extracts, fractions, and isolated compounds of P. utilis exhibit notable antioxidant, anti‐inflammatory, antimicrobial, enzymatic inhibitory, immunosuppressive, and cytotoxic properties. In vivo studies confirm its traditional uses, demonstrating anti‐inflammatory, anti‐benign prostatic hyperplasia, osteoprotective, and hypoglycemic effects. Effective formulations using P. utilis extract have been developed for atrophic dermatitis and acne vulgaris. These findings underscore the plant's potential as a source of new therapeutic agents and functional additives. Nonetheless, further research is essential to advance pharmacological assessments, clinical trials, and sustainable cultivation methods to fully harness its pharmaceutical and industrial applications.

Correlation analysis between phytochemical composition and biological activities of Artemisiascoparia

As a homologous plant of medicine and food, Artemisia scoparia has rich nutritional value and medicinal components. The main contents are to analyze the phytochemical composition and various biological activities of A. scoparia, and to explore the Pearson correlation between the contents of each phytochemical composition and biological activities. The ethanol extract (EA) and its fractions (n-hexane extract (NHE), ethyl acetate extract (EAC), n-butanol extract (NBA), and water extract (HO)) of A. scoparia were rich in polyphenols, polysaccharides, terpenoids, coumarins, flavonoids and showed potential for antibacterial, antioxidant, hypoglycemic, lipid-lowering, and anti-inflammatory activities. EAC contains the highest amount of coumarins and flavonoids, shows strong antibacterial, antioxidant, hypoglycemic, lipid-lowering and anti-inflammatory (COX-2) activities. In addition, the inhibition rate of NHE on LOX was higher, and Pearson correlation reveled a strong association between phytochemical composition and biological activities: Coumarins had antimicrobial properties, flavonoids had antioxidant and hypoglycemic effects, and flavonoids and terpenoids had anti-inflammatory effects. There was a significant negative correlation between coumarins and MBC of S. aureus (r = 0.84, p < 0.001) and C. albicans (r = 0.84, p < 0.001). Flavonoids (r = 0.86, p < 0.001) showed a significant negative correlation with α-glucosidase scavenging ability. Terpenoids also showed a significantly negative correlation with LOX scavenging ability (r = 0.70, p < 0.001). A comprehensive understanding of both physiological functionalities and potential applications related to the bioactive elements present in extracts from A. scoparia could potentially provide valuable scientific insights to guide its medical or health-related utilization.

Efficacy and safety of cofrogliptin once every 2 weeks in Chinese patients with type 2 diabetes: A randomized, double-blind, placebo-controlled, phase 3 trial.

We conducted a multicentre, randomized phase 3 trial in China to evaluate the efficacy and safety of cofrogliptin (HSK7653), a novel long-acting dipeptidyl peptidase-4 inhibitor, in patients with drug-naïve type 2 diabetes (T2D). Patients with inadequately controlled T2D were randomly assigned (1:1:1) to cofrogliptin 10 mg, cofrogliptin 25 mg or placebo, taken orally once every 2 weeks for a 24-week double-blind period. Eligible patients then received cofrogliptin 25 mg in a 28-week open-label extension. The primary endpoint was the change in glycated haemoglobin (HbA1c) from baseline to week 24. In total, 475 patients (median age: 54.0 years) were randomized and received at least one dose of cofrogliptin 10 mg (n = 158), cofrogliptin 25 mg (n = 158) or placebo (n = 159); 401 patients entered the open-label extension. At week 24, the least-squares (LS) mean difference (95% confidence interval [CI]) in HbA1c versus placebo was -0.63% (-0.81, -0.46) with cofrogliptin 10 mg and -0.59% (-0.77, -0.42) with cofrogliptin 25 mg (both p < 0.0001). The LS mean (standard error) change in HbA1c from baseline was maintained at the end of the study in patients given open-label cofrogliptin 25 mg for an additional 28 weeks: cofrogliptin 10 mg: -0.86% (0.07); cofrogliptin 25 mg: -0.74% (0.07); placebo: -0.89% (0.07). Over the entire study, common adverse events were hyperuricaemia, hyperlipidaemia, hypertriglyceridaemia, increased lipase, upper respiratory tract infection and urinary tract infection. Hypoglycaemic events did not significantly differ between groups. Cofrogliptin provided glycaemic control over 52 weeks and was generally well tolerated in patients with T2D. Registered on Clinicaltrials.gov with the registration number NCT04556851 (https://clinicaltrials.gov/study/NCT04556851).

Loureirin B Ameliorates Glycolipid Metabolism Disorders in Ob/ob Mice by Regulating Bile Acid Levels and Modulating Gut Microbiota Composition.

Loureirin B (LB), an active component of Resina Draconis, exhibits hypoglycemic and hypolipidemic effects; however, its mode of action remains unclear. Here, ob/ob mice were utilized to investigate the effects of LB on the regulation of glucolipid metabolism disorders. Non-targeted metabolomics and 16S rDNA sequencing were performed to elucidate the potential mechanisms involved. Results indicated that LB treatment (45 mg/kg) significantly improved glucose intolerance and insulin resistance, reduced lipid levels, and alleviated hepatic steatosis. Non-targeted metabolomics analysis revealed that LB treatment regulated bile acid levels. Quantification of liver bile acids demonstrated that LB treatment significantly decreased the ratio of 12α-OH to non-12α-OH bile acids in the liver. 16S rDNA sequencing results showed that LB treatment increased the abundance of short-chain fatty acid-producing microbiota while decreasing the abundance of bile salt hydrolase (BSH) enzyme-producing microbiota. In conclusion, LB ameliorates glucolipid metabolism disorders by regulating liver bile acid levels and modulating the composition of the gut microbiota.

Exploring the Potential Antidiabetic Effects of Alkannin (A Naphthoquinone Compound): In Vivo and In Silico Studies

Background It is estimated that the plant has been utilized in India’s traditional medical system for close to 2,500 years. Alkanin is a key active component in Boraginaceae medicinal plant roots. Many scientists are interested in this tiny molecule due to its biological potential. Purpose To examine the hypoglycemic effects of alkannin (a naphthoquinone pigment). Methods Initially, we determined the dosage of alkannin by conducting an acute oral toxicity study per Organisation for Economic Co-operation and Development guidelines. Subsequently, streptozocin was used to induce diabetes in mice, and we chose several parameters such as body weight, food and water intake, blood glucose level, and biochemical estimation for the in vivo evaluation. The enhanced pharmacokinetic features of alkannin, such as its better cytochromes P450 metabolism profiles and higher intestinal absorption as compared to glimepiride, were validated by in silico investigations utilizing Swiss ADME (Absorption, Distribution, Metabolism, and Excretion) and AutoDock Vina. Results In particular, blood glucose levels and body weight in the alkannin-treated group drastically decreased to 138 ± 1.45 mg/dL and 27.9±0.54 g, respectively, as compared with the diabetic-treated group. Moreover, alkaline phosphatase levels dropped to 57.26 ± 3.05 U/L in the alkannin group, suggesting enhanced liver and kidney functions. Creatinine levels also decreased from 1.44 ± 0.10 mg/dL to 0.92 ± 0.09 mg/dL, and serum glutamic oxaloacetic transaminase/aspartate aminotransferase levels decreased from 64.16 ± 3.14 U/L to 47.85 ± 2.01 U/L. Additionally, diabetic controls maintained cholesterol levels between 102.1 ± 11.46 mg/dL and 93.53 ± 2.61 mg/dL. With a considerable binding score of –9.2 kcal/mol for alkannin, molecular docking demonstrated a high degree of binding efficiency and robust interaction with biological targets. The docking results revealed that alkannin exhibits drug-like properties. In addition, it satisfies the lead likeness requirement and has a lower synthetic accessibility score compared to glimepiride. Conclusion The results revealed the promising characteristics and positive outcomes of alkannin, underscoring its potential as a viable candidate for further investigation and prospective advancement as a treatment drug for diabetes.

Development and evaluation of biocompatible coated microneedle array for controlled insulin delivery: Fabrication, characterization, in vitro, and in vivo investigations

Traditional insulin administration for people with diabetes often involves painful injections, leading to discomfort and challenges with patient compliance. A promising alternative to these conventional methods is transdermal insulin delivery using microneedle arrays, which offer a more comfortable way to deliver insulin through the skin. This study introduces an innovative approach using 3D-printed microneedle arrays coated with insulin via a dip-coating process. These microneedles present a compelling alternative to traditional injections, particularly due to their ability to gently pierce the stratum corneum, the outermost layer of skin, while minimizing discomfort. The microneedle arrays were fabricated using biocompatible resin polymers through 3D printing, creating solid conical needles with a length of 1200 µm, a base diameter of 200 µm, a tip diameter of 80 µm, and a needle spacing of 1.2 mm. The insulin coating was achieved by dip-coating the microneedles in a solution of insulin and polyvinyl alcohol (PVA), with careful optimization of the solution concentration, immersion time, and withdrawal speed to ensure a uniform and controlled coating thickness. Mechanical stability and skin penetration capabilities of the microneedles were assessed using skin models such as parafilm and porcine skin. The tests confirmed that the coated microneedles are robust enough to consistently penetrate the skin. In vivo studies with diabetic rats were conducted to evaluate skin irritation, penetration, and drug delivery efficiency. The insulin-coated microneedle arrays successfully penetrated the skin and delivered the drug with approximately 90 % efficiency. The study also showed that the microneedles provided consistent drug delivery, and the skin recovered without any signs of injury. Additionally, the hypoglycemic effect of the insulin-coated microneedles was comparable to that of traditional subcutaneous insulin injections. These findings underscore the potential of microneedle arrays as a painless and effective method for insulin delivery, maintaining stable glucose levels over an extended period. The demonstrated safety and efficacy of the coated microneedles open the door for clinical trials and potential use in diabetic patients, offering a promising advancement in diabetes management.

Eighteen-Month Hybrid Closed-Loop Use in Very Young Children With Type 1 Diabetes: A Single-Arm Multicenter Trial.

We aimed to evaluate the longer-term safety and efficacy of hybrid closed-loop (CL) therapy in very young children with type 1 diabetes (T1D). Following a 16-week multinational, randomized crossover trial comparing hybrid CL with sensor-augmented pump (SAP) therapy in 74 very young children aged 1-7 years with T1D, participants were invited to an extension phase using CL for a further 18 months. Outcomes were compared with the primary-phase SAP period and primary-phase CL period. After the primary study phase, 60 participants were eligible to enroll in the extension. Of these, 49 consented (mean ± SD age 6.6 ± 1.5 years) to continue use of CL for 18 months. Percentage time in range (TIR) 3.9-10.0 mmol/L was 8.4 percentage points (95% CI 6.7 to 10.1; P < 0.001) higher, while HbA1c was 0.4% ([5.0 mmol/mol], 95% CI 0.3 to 0.6 [3.7 to 6.2]; P < 0.001) lower during the CL extension phase compared with primary-phase SAP period. At 18 months, mean HbA1c was 6.7 ± 0.5% and TIR was 70 ± 7%, compared with 6.7 ± 0.5% and 71 ± 6% in the primary-phase CL period. Time in hypoglycemia (<3.9 mmol/L) was similar between CL extension phase and both primary-phase SAP (P = 0.31) and CL periods (P = 0.70). There were two severe hypoglycemia events and one other serious adverse event during the extension phase. One unexpected serious adverse device effect occurred. Use of the Cambridge hybrid CL system led to sustained improvements in glycemic control lasting more than 18 months in very young children with T1D.

Proposed mechanisms of action participating in the hypoglycemic effect of the traditionally used Croton guatemalensis Lotsy and junceic acid, its main compound.

Croton guatemalensis Lotsy (Euphorbiaceae) is an important traditional medicine that is used by the Cakchiquels of Guatemala to control hyperglycemia in patients with type 2 diabetes. Previous studies have shown that administration of this plant induces an acute hypoglycemic effect during fasting and that the main compound is junceic acid, a diterpenoid with a clerodane skeleton; however, junceic acid has not been reported to have hypoglycemic activity in the literature. As the mechanisms involved in the hypoglycemic effect of C. guatemalensis remain unknown, the objective of the present investigation was to elucidate the hypoglycemic mechanisms of this species, as well as its major compound, junceic acid. The results indicated that, similar to complete extract, junceic acid exhibited a hypoglycemic effect in hyperglycemic rats. Both C. guatemalensis extract and junceic acid inhibited the activity of two rate-limiting enzymes involved in hepatic glucose production; however, compared with chlorogenic acid, junceic acid had a more potent effect on glucose-6-phosphatase levels than chlorogenic acid, which was used as a positive control. Furthermore, both fasting and postprandial insulin levels decreased in healthy and hyperglycemic rats despite reduced blood glucose levels in both metabolic states, suggesting a potential insulin-sensitizing effect. However, neither of these compounds potentiated the effect of insulin in insulin tolerance tests nor inhibited the enzyme activity of protein tyrosine phosphatase 1B, a negative regulator of the insulin pathway. Therefore, the insulin-sensitizing effect is thought to be independent of insulin and mediated by potential activation of the AMP-activated protein kinase pathway. The specific activation of this master regulator in β-cells results in the inhibition of insulin secretion in a healthy state and the restoration of the insulin response under conditions of glucotoxicity; these effects were observed after the administration of the extract and junceic acid in healthy and hyperglycemic rats. Overall, the main findings of this study establish a basis of the mechanisms of action of C. guatemalensis and its main compound, junceic acid, in terms of their hypoglycemic effect.

Don´t give up on mitochondria as a target for the treatment of diabetes and its complications

In this editorial, we discuss an article by Wang et al , focusing on the role of mitochondria in peripheral insulin resistance and insulin secretion. Despite numerous in vitro and pre-clinical studies supporting the involvement of mitochondrial dysfunction and oxidative stress in the pathogenesis of diabetes and its complications, efforts to target mitochondria for glycemic control in diabetes using mitochondria-targeted antioxidants have produced inconsistent results. The intricate functionality of mitochondria is summarized to underscore the challenges it poses as a therapeutic target. While mitochondria-targeted antioxidants have demonstrated improvement in mitochondrial function and oxidative stress in pre-clinical diabetes models, the results regarding glycemic control have been mixed, and no studies have evaluated their hypoglycemic effects in diabetic patients. Nonetheless, pre-clinical trials have shown promising outcomes in ameliorating diabetes-related complications. Here, we review some reasons why mitochondria-targeted antioxidants may not function effectively in the context of mitochondrial dysfunction. We also highlight several alternative approaches under development that may enhance the targeting of mitochondria for diabetes treatment.

The Emerging Role of GLP-1 Agonists in Burn Care: What Do We Know?

Glucagon-like peptide-1 (GLP-1) agonists mimic the action of GLP-1, a hormone that regulates blood glucose levels via stimulation of insulin release and inhibition of glucagon secretion. After burn, the current literature suggests that the use of GLP-1 agonists results in less insulin dependence with similar glucose control and hypoglycemic events to patients receiving a basal-bolus insulin regimen. GLP-1 agonists may also promote wound healing through various mechanisms including angiogenesis and improved keratinocyte migration. Despite the potential benefits, GLP-1 agonists reduce gastrointestinal motility which impacts their widespread adoption in burn care. This dysmotility can result in inadequate nutrition delivery, unintentional weight loss, and is a potential aspiration risk. The net impact of these medications on burn patients is unclear. Given their potential to demonstrate the safety, efficacy, and optimal dosing of various GLP-1 agonists in acute burn management.

Research Progress on the Quality, Extraction Technology, Food Application, and Physiological Function of Rice Bran Oil.

Rice bran oil is recommended by the World Health Organization as one of the three major healthy edible oils (along with corn and sesame oils), owing to its unique fatty acid composition and functional components. This study screened, organized, and analyzed a large number of studies retrieved through keyword searches, and investigated the nutritional value and safety of rice bran oil. It reviews the stability of raw rice bran materials and the extraction and refining process of rice bran oil and discusses food applications and sub-health regulations. Research has found that a delayed stabilization treatment of rice bran seriously affects the overall quality of rice bran oil. Compared with traditional solvent extraction, the new extraction technologies have improved the yield and nutritional value of rice bran oil, but most of them are still in the research stage. Owing to the lack of economical and applicable supporting production equipment, extraction is difficult to industrialize, which is a challenging research area for the future. Rice bran oil has stronger antioxidant stability than other edible oils and is more beneficial to human health; however, its application scope and consumption are limited owing to the product price and lack of understanding. Rice bran oil has significant antioxidant, anti-inflammatory, anti-cancer, hypoglycemic, lipid-lowering, and neuroprotective effects. Further exploratory research on other unknown functions is required to lay a scientific basis for the application and development of rice bran oil.