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Search Results (421)

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Keywords = insulin delivery

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12 pages, 1185 KiB  
Article
Evaluating Insulin Delivery Systems Using Dynamic Glucose Region Plots and Risk Space Analysis
by Klavs W. Hansen, Mia Christensen, Sanne Fisker, Ermina Bach and Bo M. Bibby
Sensors 2025, 25(15), 4788; https://doi.org/10.3390/s25154788 - 4 Aug 2025
Viewed by 121
Abstract
Simultaneous values of glucose rate of change (RoC) and glucose can be presented in a dynamic glucose region plot, and risk spaces can be specified for (RoC, glucose) values expected to remain in the target range (glucose 3.9–10.0 mmol/L) or leave or return [...] Read more.
Simultaneous values of glucose rate of change (RoC) and glucose can be presented in a dynamic glucose region plot, and risk spaces can be specified for (RoC, glucose) values expected to remain in the target range (glucose 3.9–10.0 mmol/L) or leave or return to the target range within the next 30 min. We downloaded continuous glucose monitoring (CGM) data for 60 days from persons with type 1 diabetes using two different systems for automated insulin delivery (AID), A (n = 65) or B (n = 85). The relative distribution of (RoC, glucose) values in risk spaces was compared. The fraction of all (RoC, glucose) values anticipated to remain in the target range in the next 30 min was higher with system A (62.5%) than with system B (56.8%) (difference 5.7, 95% CI (2.2–9.2%), p = 0.002). The fraction of (RoC, glucose) values in the target range with a risk of progressing to the above range (glucose > 10.0 mmol/L) was slightly lower in system A than in B (difference −1.1 (95% CI: −1.8–−0.5%, p < 0.001). Dynamic glucose region plots and the concept of risk spaces are novel strategies to obtain insight into glucose homeostasis and to demonstrate clinically relevant differences comparing two AID systems. Full article
(This article belongs to the Section Biomedical Sensors)
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18 pages, 3020 KiB  
Article
JAK2/STAT3 Signaling in Myeloid Cells Contributes to Obesity-Induced Inflammation and Insulin Resistance
by Chunyan Zhang, Jieun Song, Wang Zhang, Rui Huang, Yi-Jia Li, Zhifang Zhang, Hong Xin, Qianqian Zhao, Wenzhao Li, Saul J. Priceman, Jiehui Deng, Yong Liu, David Ann, Victoria Seewaldt and Hua Yu
Cells 2025, 14(15), 1194; https://doi.org/10.3390/cells14151194 - 2 Aug 2025
Viewed by 302
Abstract
Adipose tissue inflammation contributes to obesity-induced insulin resistance. However, increasing evidence shows that high BMI (obesity) is not an accurate predictor of poor metabolic health in individuals. The molecular mechanisms regulating the metabolically activated M1 macrophage phenotype in the adipose tissues leading to [...] Read more.
Adipose tissue inflammation contributes to obesity-induced insulin resistance. However, increasing evidence shows that high BMI (obesity) is not an accurate predictor of poor metabolic health in individuals. The molecular mechanisms regulating the metabolically activated M1 macrophage phenotype in the adipose tissues leading to insulin resistance remain largely unknown. Although the Janus Kinase (Jak)/signal transducer and activator of transcription 3 (Stat3) signaling in myeloid cells are known to promote the M2 phenotype in tumors, we demonstrate here that the Jak2/Stat3 pathway amplifies M1-mediated adipose tissue inflammation and insulin resistance under metabolic challenges. Ablating Jak2 in the myeloid compartment reduces insulin resistance in obese mice, which is associated with a decrease in infiltration of adipose tissue macrophages (ATMs). We show that the adoptive transfer of Jak2-deficient myeloid cells improves insulin sensitivity in obese mice. Furthermore, the protection of obese mice with myeloid-specific Stat3 deficiency against insulin resistance is also associated with reduced tissue infiltration by macrophages. Jak2/Stat3 in the macrophage is required for the production of pro-inflammatory cytokines that promote M1 macrophage polarization in the adipose tissues of obese mice. Moreover, free fatty acids (FFAs) activate Stat3 in macrophages, leading to the induction of M1 cytokines. Silencing the myeloid cell Stat3 with an in vivo siRNA targeted delivery approach reduces metabolically activated pro-inflammatory ATMs, thereby alleviating obesity-induced insulin resistance. These results demonstrate Jak2/Stat3 in myeloid cells is required for obesity-induced insulin resistance and inflammation. Moreover, targeting Stat3 in myeloid cells may be a novel approach to ameliorate obesity-induced insulin resistance. Full article
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9 pages, 412 KiB  
Article
Euglycemic Hyperinsulinemia Lowers Blood Pressure and Impedes Microvascular Perfusion More Effectively in Persons with Cardio-Metabolic Disease
by Zhenqi Liu, Linda A. Jahn and Eugene J. Barrett
Endocrines 2025, 6(3), 36; https://doi.org/10.3390/endocrines6030036 - 24 Jul 2025
Viewed by 349
Abstract
In healthy humans, insulin at physiological concentrations exerts acute vasodilatory actions on both resistance and terminal arterioles, leading, respectively, to increased total blood flow and the microvascular network volume being perfused. The process of increasing capillary network volume is frequently referred to as [...] Read more.
In healthy humans, insulin at physiological concentrations exerts acute vasodilatory actions on both resistance and terminal arterioles, leading, respectively, to increased total blood flow and the microvascular network volume being perfused. The process of increasing capillary network volume is frequently referred to as “capillary recruitment”. Together these two vascular actions of insulin enhance the delivery of oxygen, nutrients, and insulin itself to tissues. Both processes are diminished by insulin resistance. Here we examined interactions between insulin’s acute (within 2 h) actions on blood pressure (both central and peripheral) and on capillary recruitment in healthy controls and in four distinct groups of people with heightened cardio-metabolic disease (CMD) risk: individuals with obesity, metabolic syndrome, and type 1 or type 2 diabetes. Insulin increased microvascular blood volume (MBV) more effectively in controls than in each of the four CMD risk groups (p < 0.001). Conversely, insulin lowered both central and peripheral systolic pressure (p < 0.05 or less) in each of the CMD risk groups but not in the controls. The insulin-induced blood pressure decrements were greater in the metabolic syndrome, type 2 diabetes, and obesity groups (p < 0.05 or less) than in the controls. The greater blood pressure declines likely reflect decreased sympathetic baroreceptor reflex tone. These effects on blood pressure combined with the diminished dilation of terminal arterioles due to microvascular insulin resistance in the CMD risk subjects led to decreased distal microvascular perfusion as evidenced by changes in MBV. These findings highlight the complex interplay between insulin’s actions on resistance and terminal arterioles in individuals with a high CMD risk, underscoring the importance of addressing microvascular dysfunction in these conditions. Full article
(This article belongs to the Special Issue Feature Papers in Endocrines 2025)
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39 pages, 2934 KiB  
Review
Phytocannabinoids as Novel SGLT2 Modulators for Renal Glucose Reabsorption in Type 2 Diabetes Management
by Raymond Rubianto Tjandrawinata, Dante Saksono Harbuwono, Sidartawan Soegondo, Nurpudji Astuti Taslim and Fahrul Nurkolis
Pharmaceuticals 2025, 18(8), 1101; https://doi.org/10.3390/ph18081101 - 24 Jul 2025
Viewed by 469
Abstract
Background: Sodium–glucose cotransporter 2 (SGLT2) inhibitors have transformed type 2 diabetes mellitus (T2DM) management by promoting glucosuria, lowering glycated hemoglobin (HbA1c), blood pressure, and weight; however, their use is limited by genitourinary infections and ketoacidosis. Phytocannabinoids—bioactive compounds from Cannabis sativa—exhibit multi-target [...] Read more.
Background: Sodium–glucose cotransporter 2 (SGLT2) inhibitors have transformed type 2 diabetes mellitus (T2DM) management by promoting glucosuria, lowering glycated hemoglobin (HbA1c), blood pressure, and weight; however, their use is limited by genitourinary infections and ketoacidosis. Phytocannabinoids—bioactive compounds from Cannabis sativa—exhibit multi-target pharmacology, including interactions with cannabinoid receptors, Peroxisome Proliferator-Activated Receptors (PPARs), Transient Receptor Potential (TRP) channels, and potentially SGLT2. Objective: To evaluate the potential of phytocannabinoids as novel modulators of renal glucose reabsorption via SGLT2 and to compare their efficacy, safety, and pharmacological profiles with synthetic SGLT2 inhibitors. Methods: We performed a narrative review encompassing the following: (1) the molecular and physiological roles of SGLT2; (2) chemical classification, natural sources, and pharmacokinetics/pharmacodynamics of major phytocannabinoids (Δ9-Tetrahydrocannabinol or Δ9-THC, Cannabidiol or CBD, Cannabigerol or CBG, Cannabichromene or CBC, Tetrahydrocannabivarin or THCV, and β-caryophyllene); (3) in silico docking and drug-likeness assessments; (4) in vitro assays of receptor binding, TRP channel modulation, and glucose transport; (5) in vivo rodent models evaluating glycemic control, weight change, and organ protection; (6) pilot clinical studies of THCV and case reports of CBD/BCP; (7) comparative analysis with established synthetic inhibitors. Results: In silico studies identify high-affinity binding of several phytocannabinoids within the SGLT2 substrate pocket. In vitro, CBG and THCV modulate SGLT2-related pathways indirectly via TRP channels and CB receptors; direct IC50 values for SGLT2 remain to be determined. In vivo, THCV and CBD demonstrate glucose-lowering, insulin-sensitizing, weight-reducing, anti-inflammatory, and organ-protective effects. Pilot clinical data (n = 62) show that THCV decreases fasting glucose, enhances β-cell function, and lacks psychoactive side effects. Compared to synthetic inhibitors, phytocannabinoids offer pleiotropic benefits but face challenges of low oral bioavailability, polypharmacology, inter-individual variability, and limited large-scale trials. Discussion: While preclinical and early clinical data highlight phytocannabinoids’ potential in SGLT2 modulation and broader metabolic improvement, their translation is impeded by significant challenges. These include low oral bioavailability, inconsistent pharmacokinetic profiles, and the absence of standardized formulations, necessitating advanced delivery system development. Furthermore, the inherent polypharmacology of these compounds, while beneficial, demands comprehensive safety assessments for potential off-target effects and drug interactions. The scarcity of large-scale, well-controlled clinical trials and the need for clear regulatory frameworks remain critical hurdles. Addressing these aspects is paramount to fully realize the therapeutic utility of phytocannabinoids as a comprehensive approach to T2DM management. Conclusion: Phytocannabinoids represent promising multi-target agents for T2DM through potential SGLT2 modulation and complementary metabolic effects. Future work should focus on pharmacokinetic optimization, precise quantification of SGLT2 inhibition, and robust clinical trials to establish efficacy and safety profiles relative to synthetic inhibitors. Full article
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17 pages, 2607 KiB  
Article
One-Pot Synthesis of Phenylboronic Acid-Based Microgels for Tunable Gate of Glucose-Responsive Insulin Release at Physiological pH
by Prashun G. Roy, Jiangtao Zhang, Koushik Bhattacharya, Probal Banerjee, Jing Shen and Shuiqin Zhou
Molecules 2025, 30(15), 3059; https://doi.org/10.3390/molecules30153059 - 22 Jul 2025
Viewed by 292
Abstract
Glucose-responsive insulin delivery systems that effectively regulate insulin retention and release in response to real-time fluctuation of glucose levels are highly desirable for diabetes care with minimized risk of hypoglycemia. Herein, we report a class of glucose-sensitive copolymer microgels, prepared from a simple [...] Read more.
Glucose-responsive insulin delivery systems that effectively regulate insulin retention and release in response to real-time fluctuation of glucose levels are highly desirable for diabetes care with minimized risk of hypoglycemia. Herein, we report a class of glucose-sensitive copolymer microgels, prepared from a simple one-pot precipitation copolymerization of 4-vinylphenylboronic acid (VPBA), 2-(dimethylamino) ethyl acrylate (DMAEA), and oligo(ethylene glycol) methyl ether methacrylate (Mw = 300, MEO5MA), for gated glucose-responsive insulin release within the physiologically desirable glucose level range. The composition of the p(VPBA-DMAEA-MEO5MA) copolymer microgels were analyzed using NMR and FTIR spectra. The cis-diols of glucose can reversibly bind with the −B(OH)2 groups of the VPBA component in the microgels, resulting in the formation of negatively charged boronate esters that induce the volume phase transition of the microgels. The DMAEA component is incorporated to reduce the pKa of VPBA, thus improving the glucose sensitivity of the microgels at physiological pH. The neutral hydrophilic MEO5MA component is used to tune the onset of the glucose responsiveness of the microgels to the physiologically desirable levels. The more the MEO5MA component copolymerized in the microgels, the greater the glucose concentration required to initiate the swelling of the microgels to trigger the release of insulin. When the onset of the glucose response was tuned to 4−5 mM, the copolymer microgels retained insulin effectively in the hypo-/normo-glycemic range but also released insulin efficiently in response to the elevation of glucose levels in the hyperglycemic range, which is essential for diabetes management. The copolymer microgels display no cytotoxicity in vitro. Full article
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20 pages, 763 KiB  
Review
Therapeutic Potential of Calcium Channel Blockers in Neuropsychiatric, Endocrine and Pain Disorders
by Aarish Manzar, Aleksandar Sic, Crystal Banh and Nebojsa Nick Knezevic
Cells 2025, 14(14), 1114; https://doi.org/10.3390/cells14141114 - 20 Jul 2025
Viewed by 720
Abstract
Calcium channel blockers (CCBs), originally developed for cardiovascular indications, have gained attention for their therapeutic potential in neuropsychiatric, endocrine, and pain-related disorders. In neuropsychiatry, nimodipine and isradipine, both L-type CCBs, show mood-stabilizing and neuroprotective effects, with possible benefits in depression, bipolar disorder, and [...] Read more.
Calcium channel blockers (CCBs), originally developed for cardiovascular indications, have gained attention for their therapeutic potential in neuropsychiatric, endocrine, and pain-related disorders. In neuropsychiatry, nimodipine and isradipine, both L-type CCBs, show mood-stabilizing and neuroprotective effects, with possible benefits in depression, bipolar disorder, and schizophrenia. In endocrinology, verapamil, a non-dihydropyridine L-type blocker, has been associated with the preservation of pancreatic β-cell function and reduced insulin dependence in diabetes. CCBs may also aid in managing primary aldosteronism and pheochromocytoma, particularly in patients with calcium signaling mutations. In pain medicine, α2δ ligands and selective blockers of N-type and T-type channels demonstrate efficacy in neuropathic and inflammatory pain. However, their broader use is limited by challenges in central nervous system (CNS) penetration, off-target effects, and heterogeneous trial outcomes. Future research should focus on pharmacogenetic stratification, novel delivery platforms, and combination strategies to optimize repurposing of CCBs across disciplines. Full article
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13 pages, 551 KiB  
Article
Association of Cord Blood Metabolic Biomarkers (Leptin, Adiponectin, IGF-1) with Fetal Adiposity Across Gestation
by Junko Tamai, Satoru Ikenoue, Keisuke Akita, Keita Hasegawa, Toshimitsu Otani, Marie Fukutake, Yoshifumi Kasuga and Mamoru Tanaka
Int. J. Mol. Sci. 2025, 26(14), 6926; https://doi.org/10.3390/ijms26146926 - 18 Jul 2025
Viewed by 265
Abstract
Childhood obesity is a substantial health problem worldwide. The origin of obesity (increased adiposity) can be partly traced back to intrauterine life. However, the determinants of fetal fat deposition remain unclear. This study investigated the association between cord blood adipocytokines related to lipid [...] Read more.
Childhood obesity is a substantial health problem worldwide. The origin of obesity (increased adiposity) can be partly traced back to intrauterine life. However, the determinants of fetal fat deposition remain unclear. This study investigated the association between cord blood adipocytokines related to lipid metabolism (leptin, adiponectin, and insulin-like growth factor-1 [IGF-1]) and fetal adiposity during gestation. A prospective study was conducted in a cohort of 94 singleton pregnancies. Fetal ultrasonography was performed at 24, 30, and 36 weeks of gestation. Estimated fetal adiposity (EFA) was calculated by integrating measurements of cross-sectional arm and thigh fat area percentages and anterior abdominal wall thickness. Plasma cytokine levels and C-peptide immunoreactivity (as a proxy for fetal insulin resistance) were evaluated in cord blood samples obtained at delivery. The associations of cord blood leptin, adiponectin and IGF-1 levels with EFA at 24, 30, and 36 weeks were determined by multiple linear regression, adjusted for potential covariates. The multivariate analyses indicated that leptin was significantly correlated with EFA at 30 and 36 weeks. Leptin was also positively correlated with C-peptide immunoreactivity in the umbilical cord. Cord adiponectin levels were not associated with EFA across gestation. Cord IGF-1 levels were significantly correlated with EFA and estimated fetal body weight (EFW) at 36 weeks. In conclusion, cord leptin was associated with EFA at 30 and 36 weeks, and IGF-1 was associated with EFA at 36 and EFW at 36 weeks. In Conclusion, cord leptin was associated with EFA at 30 and 36 weeks, and IGF-1 was associated with EFA and EFW at 36 weeks. Considering the effects of leptin and IGF-1 on fetal insulin resistance and lipid metabolism, increased levels of leptin and IGF-1 are potential plasma biomarkers of increased fetal adiposity, which may predispose to infant obesity and metabolic dysfunction in later life. Full article
(This article belongs to the Special Issue Obesity: From Molecular Mechanisms to Clinical Aspects)
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12 pages, 1450 KiB  
Article
Polyhydramnios at Term in Gestational Diabetes: Should We Be Concerned?
by Mercedes Horcas-Martín, Tania Luque-Patiño, Claudia Usandizaga-Prat, Elena Díaz-Fernández, Victoria Melero-Jiménez, Luis Vázquez-Fonseca, Francisco Visiedo, José Román Broullón-Molanes, Rocío Quintero-Prado and Fernando Bugatto
Children 2025, 12(7), 920; https://doi.org/10.3390/children12070920 - 11 Jul 2025
Viewed by 449
Abstract
Background/Objectives: Pregnancies complicated by idiopathic polyhydramnios are linked to a heightened risk of numerous maternal and perinatal complications. We aim to study the implications of polyhydramnios in term pregnancies complicated with gestational diabetes mellitus (GDM). Methods: A prospective cohort study including 340 GDM [...] Read more.
Background/Objectives: Pregnancies complicated by idiopathic polyhydramnios are linked to a heightened risk of numerous maternal and perinatal complications. We aim to study the implications of polyhydramnios in term pregnancies complicated with gestational diabetes mellitus (GDM). Methods: A prospective cohort study including 340 GDM cases was conducted. An ultrasound scan was conducted at term between 37 and 40 weeks and amniotic fluid volume (AFV) was assessed by measuring the amniotic fluid index (AFI) and the single deepest pocket (SDP). Maternal demographics and obstetric and perinatal outcomes were evaluated after delivery. We performed comparisons between groups with normal AFV and polyhydramnios (AFI ≥ 24 cm or SDP ≥ 8 cm), and between groups with normal and increased AFV (AFI or SDP ≥ 75th centile). A multivariate logistic regression analysis was performed to study association between AVF measurements and adverse maternal and perinatal outcomes. Results: We found that women with GDM and polyhydramnios at term had a higher risk of maternal (54.3 vs. 27.5%, p < 0.001) and perinatal adverse outcomes (65.7% vs. 46.5%, p < 0.03). The increased AFV group showed a higher risk of fetal overgrowth (LGA: 21.4% vs. 8.2%, p < 0.001 and macrosomia: 19.8% vs. 5.4%, p < 0.001, respectively) and a lesser risk of delivering an SGA fetus (6.3% vs. 13.6%, respectively). Both AFI and SDP showed a significant correlation with newborn weight (r = 0.27; p < 0.001 and r = 0.28; p < 0.001, respectively) and newborn centile (r = 0.26; p < 0.001 and r = 0.26 for both). Subsequent to conducting a multivariate logistic regression analysis adjusted for pregestational BMI, nulliparity, and insulin treatment, both AFI and SDP were significantly associated with perinatal complications, but AFI showed a stronger association with fetal overgrowth (aOR 1.11; p = 0.004 for a LGA fetus and aOR 1.12; p = 0.002 for macrosomia) and with lower risk of delivering an SGA fetus (aOR 0.89; p = 0.009) or IUGR fetus (aOR 0.86; p = 0.03). ROC analysis showed a poor diagnostic performance of both AFI and SDP for identifying macrosomia (AUC 0.68 for AFI, and 0.65 for SDP). Conclusions: Detection of polyhydramnios at term, whether using AFI or SDP, identifies a subgroup of women with gestational diabetes with higher risks of obstetric and perinatal complications. Cases with increased AFV (AFI ≥ 18 cm or SDP ≥ 6.5 cm) are also associated with an increased risk of fetal overgrowth and may require more intensive monitoring for management and optimal delivery timing, with the aim of improve perinatal outcomes. Full article
(This article belongs to the Special Issue Advances in Prenatal Diagnosis and Their Impact on Neonatal Outcomes)
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16 pages, 5542 KiB  
Article
Anti-Obesity and Metabolic Effects of Forskolin in Obese C57BL/6J Mice
by Mehrnaz Abbasi, Fang Zhou, Ngoc Kim Ly, Austin Taylor, Qiaobin Hu, Jinhua Chi, Haiwei Gu and Shu Wang
Int. J. Mol. Sci. 2025, 26(14), 6607; https://doi.org/10.3390/ijms26146607 - 10 Jul 2025
Viewed by 474
Abstract
Forskolin (FSK) induces the browning of white adipose tissue (WAT) through the activation of adenylate cyclase (AC) and cyclic adenosine monophosphate (cAMP) generation. When administered intravenously or orally, FSK undergoes significant metabolism and accumulation in the liver and other tissues, resulting in high [...] Read more.
Forskolin (FSK) induces the browning of white adipose tissue (WAT) through the activation of adenylate cyclase (AC) and cyclic adenosine monophosphate (cAMP) generation. When administered intravenously or orally, FSK undergoes significant metabolism and accumulation in the liver and other tissues, resulting in high side effects and low anti-obesity effects due to trivial amounts reaching WAT. This study examines the potential anti-obesity and metabolic effects of the inguinal WAT (IWAT) delivery of FSK in high-fat diet-induced C57BL/6J obese mice. Mice received one of the following treatments twice weekly for 4 weeks: 1. Control into both IWAT depots (Conboth); 2. FSK 15 mg/kg body weight (BW)/injection into both inguinal WAT (IWAT) depots (FSK15both); 3. FSK 7.5 mg/kg BW/injection into both IWAT depots (FSK7.5both); and 4. FSK 7.5 mg/kg BW/injection into the left IWAT depot (FSK7.5left). Both the FSK15both and FSK7.5both treatments improved metabolic parameters by lowering blood glucose, enhancing glucose tolerance, and reducing serum insulin and cholesterol. The FSK15both treatment had a greater impact on IWAT, resulting in smaller adipocytes and increased expression of Ucp1 and Tmem26 mRNA levels. All FSK treatments also reduced inflammatory and lipogenic markers in the liver, indicating improved hepatic metabolism. These findings suggest that local delivery of FSK into subcutaneous WAT is a potential strategy for combating obesity and improving metabolic health. However, further studies are needed to confirm the statistical and biological significance of these effects. Full article
(This article belongs to the Section Molecular Endocrinology and Metabolism)
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30 pages, 2043 KiB  
Review
Berberine as a Bioactive Alkaloid: Multi-Omics Perspectives on Its Role in Obesity Management
by Bartłomiej Zieniuk and Magdalena Pawełkowicz
Metabolites 2025, 15(7), 467; https://doi.org/10.3390/metabo15070467 - 9 Jul 2025
Viewed by 854
Abstract
Berberine, a bioactive isoquinoline alkaloid derived from medicinal plants such as Berberis and Coptis species, shows significant promise for managing obesity and associated metabolic disorders. This review synthesizes evidence on its modulation of AMP-activated protein kinase (AMPK) signaling, gut microbiota composition, lipid metabolism, [...] Read more.
Berberine, a bioactive isoquinoline alkaloid derived from medicinal plants such as Berberis and Coptis species, shows significant promise for managing obesity and associated metabolic disorders. This review synthesizes evidence on its modulation of AMP-activated protein kinase (AMPK) signaling, gut microbiota composition, lipid metabolism, and adipokine networks, elucidating how these actions converge to suppress adipogenesis and improve insulin sensitivity. Metabolomic profiling reveals critical shifts in bile acid metabolism, short-chain fatty acid production, and mitochondrial function. Recent studies also highlight berberine’s anti-inflammatory effects and regulatory influence on glucose homeostasis. Despite its promise, challenges in oral bioavailability and drug interactions necessitate the development of advanced delivery strategies. We further discuss nanoformulations and multi-omics approaches, which integrate data from genomics, transcriptomics, proteomics, and metabolomics, provide new insights into berberine’s mechanisms, and may guide personalized therapeutic applications. While promising, further studies are needed to validate these findings in humans and translate them into effective clinical strategies. Full article
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17 pages, 2822 KiB  
Article
Rat Islet pECM Hydrogel-Based Microencapsulation: A Protective Niche for Xenotransplantation
by Michal Skitel Moshe, Stasia Krishtul, Anastasia Brandis, Rotem Hayam, Shani Hamias, Mazal Faraj, Tzila Davidov, Inna Kovrigina, Limor Baruch and Marcelle Machluf
Gels 2025, 11(7), 517; https://doi.org/10.3390/gels11070517 - 2 Jul 2025
Viewed by 588
Abstract
Type 1 diabetes (T1D) is caused by autoimmune-mediated destruction of pancreatic β-cells, resulting in insulin deficiency. While islet transplantation presents a potential therapeutic approach, its clinical application is impeded by limited donor availability and the risk of immune rejection. This study proposes an [...] Read more.
Type 1 diabetes (T1D) is caused by autoimmune-mediated destruction of pancreatic β-cells, resulting in insulin deficiency. While islet transplantation presents a potential therapeutic approach, its clinical application is impeded by limited donor availability and the risk of immune rejection. This study proposes an innovative islet encapsulation strategy that utilizes decellularized porcine pancreatic extracellular matrix (pECM) as the sole biomaterial to engineer bioactive, immunoprotective microcapsules. Rat islets were encapsulated within pECM-based microcapsules using the electrospray technology and were compared to conventional alginate-based microcapsules in terms of viability, function, and response to hypoxic stress. The pECM microcapsules maintained a spherical morphology, demonstrating mechanical robustness, and preserving essential ECM components (collagen I/IV, laminin, fibronectin). Encapsulated islets exhibited sustained viability and superior insulin secretion over a two-week period compared to alginate controls. The expression of key β-cell transcription factors (PDX1, MAFA) and structural integrity were preserved. Under hypoxic conditions, pECM microcapsules significantly reduced islet apoptosis, improved structural retention, and promoted functional recovery, likely due to antioxidant and ECM-derived cues inherent to the pECM. In vivo transplantation in immunocompetent mice confirmed the biocompatibility of pECM microcapsules, with minimal immune responses, stable insulin/glucagon expression, and no adverse systemic effects. These findings position pECM-based microencapsulation as a promising strategy for creating immunoprotective, bioactive niches for xenogeneic islet transplantation, with the potential to overcome current limitations in cell-based diabetes therapy. Full article
(This article belongs to the Special Issue Gels for Biomedical Applications)
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18 pages, 657 KiB  
Review
Pregnancy and Neonatal Outcomes in Maturity-Onset Diabetes of the Young: A Systematic Review
by Franciszek Ługowski, Julia Babińska, Katarzyna Makowska, Artur Ludwin and Paweł Jan Stanirowski
Int. J. Mol. Sci. 2025, 26(13), 6057; https://doi.org/10.3390/ijms26136057 - 24 Jun 2025
Viewed by 609
Abstract
Maturity-onset diabetes of the young (MODY)—a monogenic form of diabetes—accounts for approximately 1–2% of all diabetes cases, with GCK-MODY being the second most commonly diagnosed type. Although the inherited nature of the disease implies that the interplay between maternal glycemia and fetal genotype [...] Read more.
Maturity-onset diabetes of the young (MODY)—a monogenic form of diabetes—accounts for approximately 1–2% of all diabetes cases, with GCK-MODY being the second most commonly diagnosed type. Although the inherited nature of the disease implies that the interplay between maternal glycemia and fetal genotype directly influences neonatal outcomes, clinical guidelines for MODY-complicated pregnancies remain underdeveloped. A systematic literature search in the PubMed, Scopus, Web of Science, and Cochrane databases was conducted following the PRISMA guidelines. The study protocol has been logged in the PROSPERO registry with the identification number CRD42024609390. Data, such as MODY type, the gestational age at delivery, mode of delivery, insulin administration, mutational status of the fetus, fetal birthweight (FBW), occurrence of small-/large-for-gestational age fetus, shoulder dystocia, and neonatal hypoglycemia, were extracted and evaluated. Among 19 studies selected for the final analysis, 15 investigated perinatal outcomes in the GCK-MODY variant. Women diagnosed with GCK-MODY treated with insulin delivered approximately 1–2 weeks earlier than those managed with diet alone. FBW was significantly higher in GCK-negative as compared to GCK-positive offspring. Accordingly, fetal macrosomia was notably more common among unaffected neonates. In GCK-affected fetuses, insulin therapy was associated with a significantly lower FBW. Fetal genotype critically modifies perinatal outcomes in GCK-MODY pregnancies. In the absence of fetal genotyping, conservative management should be prioritized to mitigate the risks of fetal growth restriction and iatrogenic prematurity. As data regarding other types of MODY in pregnancy remain sparse, there is an urgent need for more research in this area. Full article
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30 pages, 3428 KiB  
Review
Lipid-Polymer Hybrid Nanoparticles as a Smart Drug Delivery System for Peptide/Protein Delivery
by Alharith A. A. Hassan, Eslam Ramadan, Katalin Kristó, Géza Regdon and Tamás Sovány
Pharmaceutics 2025, 17(6), 797; https://doi.org/10.3390/pharmaceutics17060797 - 19 Jun 2025
Viewed by 1487
Abstract
The efficient oral delivery of therapeutic proteins and peptides poses a tremendous challenge due to their inherent instability, large molecular size, and susceptibility to enzymatic degradation. Several nanocarrier systems, such as liposomes, solid lipid nanoparticles, and polymeric nanoparticles, have been explored to overcome [...] Read more.
The efficient oral delivery of therapeutic proteins and peptides poses a tremendous challenge due to their inherent instability, large molecular size, and susceptibility to enzymatic degradation. Several nanocarrier systems, such as liposomes, solid lipid nanoparticles, and polymeric nanoparticles, have been explored to overcome these problems. Liposomes and other lipid-based nanocarriers show excellent biocompatibility and the ability to encapsulate hydrophobic and hydrophilic drugs; however, they often suffer from poor structural stability, premature leakage of the loaded drugs, and poor encapsulation efficiency for macromolecular peptides and proteins. On the other hand, polymeric nanoparticles are more stable and allow better control over drug release; nevertheless, they usually lack the necessary biocompatibility and cellular uptake efficiency. Recently, lipid-polymer hybrid nanoparticles (LPHNs) have emerged as an advanced solution combining the structural stability of polymers and the biocompatibility and surface functionalities of lipids to enhance the controlled release, stability, and bioavailability of protein and peptide drugs. In this review, an attempt was made to set a clear definition of the LPHNs and extend the concept and area, so to our knowledge, this is the first review that highlights six categories of the LPHNs based on their anatomy. Moreover, this review offers a detailed analysis of LPHN preparation methods, including conventional and nonconventional one-step and two-step processes, nanoprecipitation, microfluidic mixing, and emulsification methods. Moreover, the material attributes and critical process parameters affecting the output of the preparation methods were illustrated with supporting examples to enable researchers to select the suitable preparation method, excipients, and parameters to be manipulated to get the LPHNs with the predetermined quality. The number of reviews focusing on the formulation of peptide/protein pharmaceutics usually focus on a specific drug like insulin. To our knowledge, this is the first review that generally discusses LPHN-based delivery of biopharmaceuticals. by discussing representative examples of previous reports comparing them to a variety of nanocarrier systems to show the potentiality of the LPHNs to deliver peptides and proteins. Moreover, some ideas and suggestions were proposed by the authors to tackle some of the shortcomings highlighted in these studies. By presenting this comprehensive overview of LPHN preparation strategies and critically analyzing literature studies on this topic and pointing out their strong and weak points, this review has shown the gaps and enlightened avenues for future research. Full article
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19 pages, 469 KiB  
Review
Digital Health in Diabetes Care: A Narrative Review from Monitoring to the Management of Systemic and Neurologic Complications
by Elisabetta Maida, Paola Caruso, Simona Bonavita, Gianmarco Abbadessa, Giuseppina Miele, Miriam Longo, Lorenzo Scappaticcio, Eleonora Ruocco, Francesca Trojsi, Katherine Esposito, Luigi Lavorgna and Maria Ida Maiorino
J. Clin. Med. 2025, 14(12), 4240; https://doi.org/10.3390/jcm14124240 - 14 Jun 2025
Viewed by 1121
Abstract
Background/Objectives: Despite the recent advances in glucose-lowering therapy, achieving diabetes control remains challenging. With the advancing progress of innovative digital health technologies, management of diabetes is taking advantage from telehealth and telemedicine, which allow for remote assistance, virtual visits, and monitoring of [...] Read more.
Background/Objectives: Despite the recent advances in glucose-lowering therapy, achieving diabetes control remains challenging. With the advancing progress of innovative digital health technologies, management of diabetes is taking advantage from telehealth and telemedicine, which allow for remote assistance, virtual visits, and monitoring of diabetes-related parameters, and facilitate the exchange of documents and reports to support clinical decisions. We aim to provide an overview of the impact of telehealth and digital technologies on the care of people with diabetes, from therapeutic management to the assessment of complications. Methods: A comprehensive literature search was conducted using PubMed to assess the impact of digital technologies and telemedicine on diabetes care. Results: From the comprehensive PubMed search, 86 peer-reviewed studies were selected based on relevance, clinical significance, and methodological quality. The selected literature addressed digital health tools such as continuous glucose monitoring, connected insulin pens, automatic insulin delivery systems, mobile applications, and telemedicine systems. These interventions were associated with improved glycemic control (e.g., reduced HbA1c, increased time in range), better adherence to therapy, enhanced patient engagement, and more efficient management of complications such as neuropathy, retinopathy, and cardiovascular risk. Conclusions: Telehealth may offer a fully patient-centered approach to disease management through a tailored individual management plan. This may lead to an improvement in adherence to proper therapy and lifestyle, resulting in a subsequent increase in the quality of life. Full article
(This article belongs to the Section Endocrinology & Metabolism)
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27 pages, 1992 KiB  
Review
Revolutionizing Diabetes Management Through Nanotechnology-Driven Smart Systems
by Aayush Kaushal, Aanchal Musafir, Gourav Sharma, Shital Rani, Rajat Kumar Singh, Akhilesh Kumar, Sanjay Kumar Bhadada, Ravi Pratap Barnwal and Gurpal Singh
Pharmaceutics 2025, 17(6), 777; https://doi.org/10.3390/pharmaceutics17060777 - 13 Jun 2025
Viewed by 1147
Abstract
Diabetes is a global health challenge, and while current treatments offer relief, they often fall short in achieving optimal control and long-term outcomes. Nanotechnology offers a groundbreaking approach to diabetes management by leveraging materials at the nanoscale to improve drug delivery, glucose monitoring, [...] Read more.
Diabetes is a global health challenge, and while current treatments offer relief, they often fall short in achieving optimal control and long-term outcomes. Nanotechnology offers a groundbreaking approach to diabetes management by leveraging materials at the nanoscale to improve drug delivery, glucose monitoring, and therapeutic precision. Early advancements focused on enhancing insulin delivery through smart nanosystems such as tiny capsules that gradually release insulin, helping prevent dangerous drops in blood sugar. Simultaneously, the development of nanosensors has revolutionised glucose monitoring, offering real-time, continuous data that empowers individuals to manage their condition more effectively. Beyond insulin delivery and monitoring, nanotechnology enables targeted drug delivery systems that allow therapeutic agents to reach specific tissues, boosting efficacy while minimising side effects. Tools like microneedles, carbon nanomaterials, and quantum dots have made treatment less invasive and more patient-friendly. The integration of artificial intelligence (AI) with nanotechnology marks a new frontier in personalised care. AI algorithms can analyse individual patient data to adjust insulin doses and predict glucose fluctuations, paving the way for more responsive, customised treatment plans. As these technologies advance, safety remains a key concern. Rigorous research is underway to ensure the biocompatibility and long-term safety of these novel materials. The future of diabetes care lies in the convergence of nanotechnology and AI, offering personalised, data-driven strategies that address the limitations of conventional approaches. This review explores current progress, persistent challenges, and the transformative potential of nanotechnology in reshaping diabetes diagnosis and treatment and improving patient quality of life. Full article
(This article belongs to the Special Issue Delivery System for Biomacromolecule Drugs: Design and Application)
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