Search Results (1,365)

Diabetic nephropathy (DN) is a major complication of chronic hyperglycemia. Although fish gelatin hydrolysate has antioxidant, anti-inflammatory, and antihypertensive properties, its renoprotective effects in DN remain unclear. This study investigated its effects on renal oxidative stress, inflammation, fibrosis, and endoplasmic reticulum (ER) stress in diabetic rats. Thirty male Wistar rats were fed a normal chow diet or a high-fat diet for 4 weeks. Diabetes was induced in high-fat-diet-fed rats by a single intraperitoneal injection of streptozotocin (30 mg/kg). Diabetic rats were randomly assigned to receive no treatment (untreated diabetes), gelatin hydrolysate at 250 or 500 mg/day, or metformin at 100 mg/kg/day groups (n = 6/group), while normal-chow-fed rats served as controls. Treatments were orally administered for 8 weeks. High-dose gelatin hydrolysate improved metabolic disturbances and renal dysfunction, whereas low-dose gelatin hydrolysate and metformin more effectively reduced oxidative stress, as indicated by decreased 8-OHdG expression. All treatments reduced renal injury, fibrosis, and inflammatory markers. ER stress-related proteins were also attenuated, with the greatest changes observed in IRE1/XBP1-associated markers. These findings provide in vivo evidence that GLH treatment is associated with improved renal outcomes and reduced markers of oxidative stress, inflammation, fibrosis, and ER stress in DM rats. Full article

Background: Diabetic retinopathy (DR) is a leading cause of vision loss, with oxidative stress and inflammation serving as critical drivers of its onset and progression. Curcumin, a natural polyphenol, is known for its potent anti-inflammatory and antioxidant properties. Glial fibrillary acidic protein (GFAP) is commonly used as an indicator of retinal macroglial reactivity, whereas the NLRP3 inflammasome is an important mediator of inflammatory signaling in DR. We evaluated retinal vascular abnormalities and retinal GFAP immunoreactivity and examined whether these findings were accompanied by changes in retinal NLRP3 and IL-1β protein abundance and in the levels of cleaved caspase-1 and cleaved GSDMD. Methods: Diabetes was induced in 7-week-old rats via a single intraperitoneal injection of streptozotocin. Following the confirmation of hyperglycemia, curcumin was administered orally. To evaluate the effects, we performed trypsin digestion, haematoxylin and eosin (H&E) staining, fluorescein isothiocyanate (FITC)–dextran permeability assays, immunofluorescence staining, and Western blotting on the harvested retinas. Results: The DM group showed increased acellular capillary formation, vascular leakage, retinal GFAP immunoreactivity, NLRP3 and IL-1β protein abundance, and levels of cleaved caspase-1 and cleaved GSDMD. Compared with the untreated DM group, the DM + curcumin group showed lower values for all of these outcomes. Conclusions: In diabetic rats, oral administration of a curcumin-containing formulation was associated with fewer retinal vascular abnormalities and lower GFAP immunoreactivity, accompanied by parallel differences in inflammasome-related proteins. These findings support the potential of this formulation as an adjunctive therapeutic approach for early diabetic retinopathy. Full article

Diabetes mellitus (DM) is a chronic metabolic disease characterized by hyperglycemia, and the diaphragm—the primary respiratory muscle—is adversely affected by this diabetic process. The aim of this study is to investigate the effects of zinc sulfate (ZnSO₄) treatment on diaphragm muscle contractile dynamics, calcium homeostasis, apoptosis, and fibrosis in an 18-month-old female Type 2 diabetic rat model. Thirty-two 18-month-old female Wistar rats were randomly divided into four groups: Control (CON), CON + ZnSO₄, Diabetes Mellitus (DM), and DM + ZnSO₄. The DM model was induced by a high-fat diet and administration of 30 mg/kg streptozotocin (STZ); after the disease was confirmed, ZnSO₄ was administered intraperitoneally at a daily dose of 10 mg/kg to the treatment groups. The mechanical functions of the diaphragm muscle were evaluated using a post-rest potentiation protocol in an isolated organ bath; qPCR analyses (Caspase-3, TGF-β1, SERCA2a) were performed to investigate cellular apoptosis, fibrosis, and calcium regulation. Compared with the CON group, the DM group exhibited a severe ~90% reduction in diaphragmatic contraction force (CF) and a ~97% decline in maximal contraction/relaxation velocities (±dF/dt_max) (p < 0.0001), which strongly correlated with a 30% suppression of SERCA2a gene expression (p < 0.01). Concomitantly, apoptotic Caspase-3 (~2.6-fold) and profibrotic TGF-β1 (~3.1-fold) mRNA levels were significantly elevated (p < 0.0001). In the DM + ZnSO₄ group, daily zinc treatment (10 mg/kg/day, i.p. for 6 weeks, initiated 4 weeks after diabetes confirmation) did not reverse the elevated Caspase-3 and TGF-β1 expressions (p > 0.05). However, SERCA2a expression was fully preserved back to control levels (p < 0.05 vs. DM), leading to a substantial ~3-fold improvement in CF and velocities (p < 0.05 to p < 0.0001 vs. DM). On the other hand, the healthy CON + ZnSO₄ group exhibited a physiological slowing of contractility (~53% decrease in CF), without histological damage, likely due to a competitive antagonism between excess divalent zinc (Zn²⁺) and calcium (Ca²⁺) on myofilaments. Although zinc cannot reverse the structural apoptotic and fibrotic remodeling in the aged diabetic diaphragm, it successfully rescues functional contractility by preserving SERCA2a transcriptional expression. Full article

Diabetes mellitus is frequently associated with gastrointestinal dysfunction, in which alterations in the enteric nervous system (ENS) are considered important contributing factors. Neuropeptide Y (NPY) is a key enteric neuromodulator involved in the regulation of gastrointestinal motility, secretion, and blood flow; however, its response to diabetes remains insufficiently characterized, particularly in large animal models. This study investigated the effect of experimental diabetes on the distribution of NPY-immunoreactive enteric neurons in the porcine gastrointestinal tract. Diabetes was induced in juvenile female pigs by streptozotocin administration. Six weeks later, the stomach, duodenum, jejunum, ileum, and descending colon were collected, and the population of NPY-immunoreactive neurons in the myenteric and submucosal plexuses was evaluated by double-label immunofluorescence. Experimental diabetes significantly increased the population of NPY-immunoreactive neurons in the myenteric plexus of the stomach, jejunum, ileum, and descending colon, whereas no statistically significant changes were detected in the duodenum after correction for multiple comparisons. In the submucosal plexuses, significant increases were restricted to the inner and outer submucosal plexuses of the descending colon. These findings demonstrate that diabetes induces region- and plexus-specific neurochemical plasticity of NPY-immunoreactive enteric neurons in pigs. Given the predominantly inhibitory effects of NPY on gastrointestinal motility and secretion, together with its vasoconstrictive actions, the observed changes may contribute to altered neural regulation of gastrointestinal function during diabetes and may represent one of the mechanisms involved in diabetic gastroenteropathy. Full article

Diabetic cardiomyopathy (DCM) is characterized by myocardial remodeling that may already be evident during prediabetes, yet the molecular alterations accompanying these early changes remain poorly understood. The present study examined mouse models of Nucleoside diphosphate kinase (NDPK-B)-deficient prediabetes and streptozotocin-induced diabetes using O-GlcNAc-associated proteomic profiling to define stage-specific molecular alterations during the progression from prediabetic to diabetic cardiomyopathy. Both models exhibited increased left ventricular extracellular matrix deposition and impaired diastolic function, together with activation of the hexosamine biosynthesis pathway. Profiling of O-GlcNAc-associated proteins uncovered extensive remodeling of the mitochondrial proteome already at the prediabetic stage, with respiratory complex I among the most prominently altered targets, alongside changes in substrate metabolism and inflammatory signaling. In overt DCM, the putative O-GlcNAc proteomic profile was associated with a shift toward wider lipid-dependent metabolic reprogramming and remodeling of mitochondrial proteins. These findings identify early remodeling of the mitochondrial O-GlcNAc-associated proteome as a molecular signature of prediabetic cardiomyopathy and highlight respiratory complex I proteins as candidate targets for future mechanistic investigations. Full article

Type 1 diabetes (T1D) is a systemic metabolic disorder associated with male reproductive dysfunction. Given the pivotal role of actin cytoskeleton remodeling in spermatogenesis and sperm function, this study investigated the effects of T1D on actin-regulating pathways in rat testis and spermatozoa (SPZ). Adult Wistar rats were rendered diabetic by streptozotocin administration (65 mg/kg, i.p.). Testicular analysis revealed a reduced F-/G-actin ratio together with marked F-actin disorganization, consistent with altered actin cytoskeleton remodeling. To investigate the molecular mechanisms underlying these alterations, key regulators of actin dynamics were examined. Diabetic animals displayed impaired expression of EPS8, Fascin, N-WASP, and the ARP2/3 complex, suggesting altered regulation of actin assembly, bundling, and branching. Further analyses demonstrated dysregulation of signaling pathways governing cytoskeletal organization. Reduced levels of phosphorylated Disheveled-2, DAAM1, RhoA-GTP, and ROCK1 indicated impairment of the planar cell polarity pathway. In parallel, changes in LIMK1/cofilin phosphorylation supported abnormal regulation of actin filament turnover. Alterations in the RICTOR/PKC/MARCKS signaling pathway further highlighted defects in cytoskeletal control. Similar abnormalities were observed in mature SPZ, where altered F-actin distribution and DAAM1 localization suggested persistent cytoskeletal defects. Moreover, diabetic SPZ exhibited a reduced ability to undergo acrosome reaction, accompanied by altered MARCKS phosphorylation, highlighting defects in actin-dependent processes essential for sperm function and fertilizing capacity. These findings indicate that disruption of actin cytoskeleton dynamics may represent a major mechanism contributing to testicular and sperm abnormalities in T1D, providing new insights into the mechanisms underlying diabetes-associated male reproductive dysfunction. Full article

Background/Objectives: This in vivo study was conducted to investigate the effects of mace water extract from Myristica fragrans Houtt (ME) on serum biochemical and histopathological profiles of normoglycemic and streptozotozin-induced hyperglycemic rats. Methods: Biochemical parameters (cholesterol, HDL, LDL, triglycerides, creatinine, blood urea nitrogen, AST, ALT, and albumin) from all groups of experimental rats were analyzed. Histopathological analysis was also performed on the kidney, liver, and pancreatic tissues. Results: The results showed that administration of ME (1.84 mg total phenolics from ME/kg BW) was able to prevent serum biochemical changes that are indicators of metabolic disorders and organ tissue damage due to hyperglycemia. ME significantly reduced LDL (31.85%), creatinine (13.78%), AST (58.97%), and ALT (60.04%) levels in hyperglycemic rats. ME also showed promising performance in protecting the kidney and liver from damage due to hyperglycemia. Conclusions: The findings in this study emphasize the potential of ME to be used as a therapeutic agent and functional ingredient. Full article

Background: Diabetic foot ulcers (DFUs) are chronic wounds characterized by persistent inflammation, oxidative stress, impaired angiogenesis, and defective extracellular matrix remodeling. Current therapeutic approaches remain insufficient for refractory diabetic wounds due to limited drug retention and inadequate regulation of the wound microenvironment. This study aimed to develop a centipede-derived protein fraction-loaded nanocapsule hybrid hydrogel for sustained bioactive delivery and diabetic wound repair. Methods: A bioactive protein fraction was isolated from processed medicinal centipede material and screened using cellular compatibility assays. The selected tropomyosin-containing protein fraction was incorporated into nanocapsules and subsequently integrated into a gallic acid-modified polyacrylamide hydrogel matrix. The physicochemical properties, antioxidant activity, rheological behavior, and protein release characteristics of the nanocapsule-hydrogel system were systematically evaluated. A streptozotocin-induced diabetic rat wound model was established to assess therapeutic efficacy through wound closure analysis, histological staining, and immunohistochemical evaluation. Results: The prepared nanocapsules exhibited a spherical morphology, nanoscale size distribution, and sustained protein delivery capability. The PAM-GA hydrogel demonstrated antioxidant activity, injectability, shear-thinning behavior, self-healing ability, and enhanced retention of protein release. In vivo experiments showed that the PT@NC@PAM-GA hydrogel significantly accelerated wound closure and promoted tissue regeneration, accompanied by enhanced angiogenesis, collagen deposition, and reduced inflammatory responses. Conclusions: The centipede-derived protein fraction-loaded nanocapsule hybrid hydrogel effectively integrates bioactive protein delivery with a multifunctional hydrogel matrix, providing a potential strategy for sustained treatment of diabetic foot ulcers. Full article

(1) Background: Impaired diabetic wound healing stems from systemic dysregulation of the wound-healing cascade under hyperglycemic conditions, producing a disordered microenvironment marked by sustained inflammation, defective angiogenesis, and aberrant extracellular matrix remodeling, multifactorial, multistage pathological interactions demanding multi-target intervention. (2) Methods: We constructed a multifunctional nanocomposite hydrogel dressing (PGAs@CDV) based on a “drug-carrier integration” strategy, targeting the dysregulated hemostasis, inflammation, and proliferation phases of diabetic wound healing. An amphiphilic micelle carrier (PNO-GA) was synthesized by covalently conjugating Panax notoginseng oligosaccharide with gallic acid, loaded with Anemoside B4 to yield drug-loaded nanomicelles (PGAs), embedded into a carboxymethyl chitosan-dopamine-vanillin hydrogel (CDV) matrix to form PGAs@CDV. We then examined how PGAs@CDV affected diabetic wound healing. (3) Results: In vitro, PGAs@CDV enhanced cell migration and angiogenic capacity, exhibited potent antioxidant activity, and promoted M1-to-M2 macrophage polarization. We tested PGAs@CDV in a streptozotocin-induced diabetic mouse wound model. Wounds treated with PGAs@CDV closed faster than those treated with the control, CDV, PNO@CDV, and AB4@CDV. Four readouts tracked this difference: hemostasis was quicker, inflammation was lower, more blood vessels formed, and collagen deposition was higher. At the pathway level, PGAs@CDV suppressed NF-κB signaling and activated PI3K/AKT/HIF-1α. These two arms map onto the anti-inflammatory and pro-angiogenic effects observed above. (4) Conclusions: This nanocomposite hydrogel integrates a bioactive carrier with a therapeutic payload to enable coordinated intervention across multiple phases of diabetic wound repair. By combining structural support with sustained pharmacological activity, it offers a promising strategy for the treatment of chronic diabetic wounds. Full article

Introduction: Diabetic retinopathy (DR) is characterized by early retinal neurodegeneration accompanied by progressive alterations of the retinal microvasculature, both exacerbated by hyperglycemia-induced oxidative stress and inflammation. Mitochondrial dysfunction critically contributes to neuronal loss and vascular impairment. The 18 kDa Translocator Protein (TSPO) is a mitochondrial outer membrane protein whose expression is increased in activated retinal glial cells and represents a promising target to modulate neuroinflammation and oxidative stress. This study evaluates the therapeutic potential of the TSPO ligand PIGA-1138 in experimental models of DR. Methods: PIGA-1138 (3 µM in vitro; 10 mg/kg/day, i.p., in vivo) was evaluated in high glucose (HG)-exposed 661W retinal cells and in streptozotocin (STZ, 150 mg/kg)-induced diabetic C57BL/6J mice. Cell viability, mitochondrial function, oxidative stress, and Nrf2, HO-1, and SOD1 expression were assessed in vitro. Retinal function and morphology were evaluated in vivo by electroretinography (ERG), visual acuity testing, and optical coherence tomography (OCT) at 30 and 60 days after diabetes induction. Results: PIGA-1138 significantly improved cell viability, reducing apoptosis (TUNEL p ≤ 0.01), preserving mitochondrial membrane potential (MitoRed p ≤ 0.01), reducing oxidative damage, and enhancing Nrf2 nuclear translocation together with HO-1 (p ≤ 0.05) and SOD1 (p ≤ 0.01) expression in HG-treated retinal cells. In diabetic mice, treatment preserved ERG responses and limited retinal thinning at 60 days (p ≤ 0.01), while showing a trend toward preserving visual acuity. Conclusions: Targeting mitochondrial TSPO with PIGA-1138 attenuates key hallmarks of DR by mitigating oxidative stress, suppressing neuroinflammation, and preserving retinal structure and function. These findings support TSPO as a potential disease-modifying target for DR. Full article

Type 2 diabetes mellitus (T2DM) is a widely distributed dysmetabolic condition increasingly linked to neurocognitive decline, neuroinflammation, oxidative stress, and neuronal apoptosis. Chronic hyperglycemia and insulin resistance disrupt homeostasis in the central nervous system, contributing to neurodegenerative processes. This study evaluated the effects of semaglutide (SMG), a glucagon-like peptide-1 receptor agonist, on T2DM-associated neurobehavioral and biochemical alterations using a rat model. T2DM was induced by nicotinamide–streptozotocin, followed by oral administration of SMG at a dose of 1.44 mg/kg for one month. Cognitive function was evaluated using the elevated plus maze (EPM) and novel object recognition (NOR) paradigms. Fasting blood glucose and body weight were monitored throughout the experiment. Neuroinflammatory markers (COX-2, TNF-α, and IL-6), oxidative stress biomarkers (MDA, GSH, and catalase), and apoptosis-associated proteins (Caspase-3, Bax, and Bcl-2) were measured in brain tissue homogenates using ELISA. Diabetic rats exhibited marked cognitive deficits, hyperglycemia, increased neuroinflammatory markers, and altered apoptosis-related biomarkers, with reduced Bcl-2 expression. Treatment with SMG significantly improved learning and memory performance, fasting blood glucose, and body weight. At the molecular level, SMG treatment was associated with lower levels of MDA, TNF-α, Bax, IL-6, COX-2, and Caspase-3, together with higher levels of Bcl-2, catalase, and GSH compared with untreated diabetic rats. Overall, oral SMG treatment was associated with improved cognitive performance and metabolic control, accompanied by attenuation of diabetes-associated neuroinflammatory, oxidative stress, and apoptosis-related alterations in brain tissue. However, the present study was not designed to distinguish direct neuroprotective effects from changes secondary to improved metabolic control. Further studies are required to clarify the underlying mechanisms and determine the translational relevance of these findings. Full article

Ficus deltoidea Jack (Moraceae), locally known as Mas Cotek, is a medicinal plant traditionally used throughout Southeast Asia for the management of diabetes mellitus. This review summarises the available evidence on the antidiabetic properties of F. deltoidea based on eleven in vitro, nine in vivo and one clinical study identified through a structured literature search. In vitro investigations show that F. deltoidea inhibits α-glucosidase and α-amylase, stimulates insulin secretion in pancreatic β-cells via both K⁺-ATP channel-dependent and -independent pathways, enhances glucose uptake in hepatocytes and adipocytes, promotes adiponectin secretion and inhibits protein tyrosine phosphatase 1B (PTP1B). Vitexin and isovitexin, the predominant C-glycosyl flavonoids in F. deltoidea leaves, appear to be the main bioactive compounds responsible for these effects. Meanwhile, in vivo studies in streptozotocin-induced diabetic rodents report dose-dependent reductions in fasting blood glucose, improved glucose tolerance, restoration of pancreatic islet architecture, modulation of hepatic gluconeogenic and glucose-metabolic genes, and protection against diabetic nephropathy and bone loss. Inter-varietal differences in chemical composition and biological activity were observed, with var. trengganuensis and var. intermedia reported as the most active. The only available clinical trial in adults with prediabetes (1000 mg/day for 8 weeks) showed a reduction in LDL and total cholesterol but no significant change in fasting blood glucose or insulin. The discrepancy between preclinical and clinical findings highlights the need for standardised extracts, pharmacokinetic studies and adequately powered clinical trials in patients with established type 2 diabetes mellitus. Full article

Background/Objectives: Type 2 diabetes mellitus (T2DM) is associated with progressive hepatic alterations, including steatosis and fibrosis, which may affect liver mechanical properties. Shear wave elastography (SWE) is a non-invasive imaging technique that enables quantitative assessment of tissue stiffness; however, its application in diabetic animal models remains limited. This study aimed to evaluate liver elasticity using SWE in a high-fat diet (HFD) and streptozotocin (STZ)-induced rat model of T2DM, using histopathological examination as the reference standard. Methods: Twenty-four rats were randomly allocated to either a control group (n = 12) or a diabetic group (n = 12). Diabetes was induced using HFD feeding followed by low-dose STZ administration. Liver elasticity was assessed in vivo using SWE at two examination sessions. Shear wave velocity measurements were obtained from eight liver regions of interest and expressed in meters per second (m/s). Following euthanasia, liver tissues were subjected to histopathological evaluation using hematoxylin and eosin, Masson’s trichrome, and periodic acid–Schiff staining. Results: Diabetic rats demonstrated marked histopathological alterations, including macrovesicular and microvesicular steatosis, hepatocellular vacuolization, increased collagen deposition, and glycogen depletion. Collagen deposition was significantly greater in diabetic animals, while glycogen content was significantly reduced (3.70 ± 1.05 vs. 26.87 ± 2.87; p < 0.05). SWE revealed consistently higher liver shear wave velocities in diabetic rats compared with controls at both examination sessions. Although liver stiffness increased over time in both groups, these changes did not reach statistical significance. Conclusions: HFD/STZ-induced diabetes was associated with increased liver stiffness and histopathological evidence of hepatic injury and fibrosis. SWE may represent a feasible non-invasive approach for assessing diabetes-related changes in liver mechanical properties. Full article

In this study, total flavonoids from Polygonum perfoliatum L. (PPTF) were extracted using ionic liquid-assisted ultrasound and purified by macroporous resin. After optimization, the total flavonoid content increased from 33.9% to 71.2%. HPLC identified hyperoside, kaempferol-3-O-rutinoside, and quercetin. In vitro experiments showed that PPTF exhibited good free radical scavenging activity and inhibitory effects on α-glucosidase and α-amylase. Within the concentration range of 3.13–12.50 μg/mL, PPTF was non-toxic to HepG2 cells and improved glucose uptake, promoted glycogen synthesis, and reduced lipid accumulation in insulin-resistant cells in a dose-dependent manner. In a type 2 diabetic mouse model induced by high-fat diet combined with streptozotocin, intragastric administration of PPTF for four weeks significantly lowered fasting blood glucose in the high-dose group, improved oral glucose tolerance and insulin sensitivity, increased hepatic and muscle glycogen, normalized serum lipid profiles, and alleviated pathological damage in the liver and pancreas. PPTF exhibits favorable hypoglycemic and lipid-regulating effects in both cellular and animal models, demonstrating its potential for development as an adjunctive functional product for glycemic management. Full article

Background/Objectives: Diabetes mellitus-induced erectile dysfunction (DMED) is characterized by severe endothelial and smooth-muscle dysfunction and reduced responsiveness to conventional therapy. Guanxinning tablet (GXN), a traditional Chinese medicine compound containing Salvia miltiorrhiza (Danshen) and Ligusticum stratum (Chuanxiong), has vascular-protective and anti-oxidative properties, but its effect on DMED remains unclear. This study evaluated whether GXN improves erectile function in a streptozotocin (STZ)-induced type 1 diabetic rat model and explored the possible involvement of PI3K/Akt/FOXO1 signaling. Methods: STZ-induced diabetic rats with ED were treated with GXN. Artery pressure (AP) and intracavernous pressure (ICP) were measured to evaluate erectile dysfunction. Western blots, immunohistochemistry, immunofluorescence, biochemical assays, TUNEL staining, RNA-seq, and in vitro HCMEC assays were performed to evaluate erectile effector cell function, oxidative stress, fibrosis, apoptosis, and PI3K/Akt/FOXO1-associated changes. Results: GXN improved erectile function in DMED rats and was associated with improved endothelial and smooth-muscle-related markers, reduced oxidative stress, attenuated fibrosis, and decreased apoptosis. RNA-seq and protein validation suggested that GXN treatment was associated with activation of PI3K/Akt/FOXO1-related signaling. In HCMECs, LY294002 (a PI3K inhibitor) partially reversed the GXN-associated improvement in cell viability and apoptosis-related markers. Conclusions: GXN ameliorated erectile dysfunction and tissue injury in STZ-induced type 1 diabetic rats, which were associated with PI3K/Akt/FOXO1 signaling. These findings support the potential of GXN as a traditional Chinese medicine compound for treating DMED. Full article