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Frontiers in Endocrinology 2023Various animal and cell culture models of diabetes mellitus (DM) have been established and utilized to study diabetic peripheral neuropathy (DPN). The divergence of... (Review)
Review
Various animal and cell culture models of diabetes mellitus (DM) have been established and utilized to study diabetic peripheral neuropathy (DPN). The divergence of metabolic abnormalities among these models makes their etiology complicated despite some similarities regarding the pathological and neurological features of DPN. Thus, this study aimed to review the omics approaches toward DPN, especially on the metabolic states in diabetic rats and mice induced by chemicals (streptozotocin and alloxan) as type 1 DM models and by genetic mutations (MKR, db/db and ob/ob) and high-fat diet as type 2 DM models. Omics approaches revealed that the pathways associated with lipid metabolism and inflammation in dorsal root ganglia and sciatic nerves were enriched and controlled in the levels of gene expression among these animal models. Additionally, these pathways were conserved in human DPN, indicating the pivotal pathogeneses of DPN. Omics approaches are beneficial tools to better understand the association of metabolic changes with morphological and functional abnormalities in DPN.
Topics: Humans; Mice; Rats; Animals; Diabetic Neuropathies; Diabetes Mellitus, Experimental; Sciatic Nerve; Diabetes Mellitus, Type 2; Diabetes Mellitus, Type 1
PubMed: 38089620
DOI: 10.3389/fendo.2023.1208441 -
Foods (Basel, Switzerland) Jul 2023Strawberry () is one of the accomplished sources of bioactive compounds, including anthocyanin, phenolic acids, flavonols, ellagitannins, and a diverse range of minerals...
Strawberry () is one of the accomplished sources of bioactive compounds, including anthocyanin, phenolic acids, flavonols, ellagitannins, and a diverse range of minerals and vitamins that can help to boost human health. This study was carried out to explore the antidiabetic, antioxidative and antihyperlipidemic potential of strawberry extracts against alloxan-induced (100 mg/kg body weight) diabetic rats. Accordingly, rats were categorized into six groups including control (G), positive control (G), treatment groups (G, G, and G) given strawberry extract at 250, 500, and 750 mg/kg of body weight, respectively, and G provided metformin @70 mg/kg BW for 28 days with ad libitum diet. At the trial termination, the rats were sacrificed and were subjected to analysis including body weight, blood glucose level and glycemic indicators, antioxidant parameters, lipid profile, renal function test (RFT), liver function test (LFT) and histopathology for pancreatic tissues. The results indicated that treatment of diabetic rats with strawberry extract at 500 mg/kg body weight (BW) resulted in significant reductions in blood glucose level, serum urea, and creatinine as well as significant increases in body weight, insulin activity, and protein levels. In addition, the diabetic rats that did not receive strawberry extract (control) exhibited an increase in plasma glucose, urea, uric acid, creatinine, and a decrease in body weight and insulin levels. Briefly, it is reported that strawberry fruit extracts reduced blood sugar levels, possess hypolipidemic potential, and helped to maintain antioxidant levels in alloxan-induced diabetic rats.
PubMed: 37569180
DOI: 10.3390/foods12152911 -
Animal Models and Experimental Medicine Jun 2024Diabetes mellitus is one of the world's most prevalent and complex metabolic disorders, and it is a rapidly growing global public health issue. It is characterized by... (Review)
Review
Diabetes mellitus is one of the world's most prevalent and complex metabolic disorders, and it is a rapidly growing global public health issue. It is characterized by hyperglycemia, a condition involving a high blood glucose level brought on by deficiencies in insulin secretion, decreased activity of insulin, or both. Prolonged effects of diabetes include cardiovascular problems, retinopathy, neuropathy, nephropathy, and vascular alterations in both macro- and micro-blood vessels. In vivo and in vitro models have always been important for investigating and characterizing disease pathogenesis, identifying targets, and reviewing novel treatment options and medications. Fully understanding these models is crucial for the researchers so this review summarizes the different experimental in vivo and in vitro model options used to study diabetes and its consequences. The most popular in vivo studies involves the small animal models, such as rodent models, chemically induced diabetogens like streptozotocin and alloxan, and the possibility of deleting or overexpressing a specific gene by knockout and transgenic technologies on these animals. Other models include virally induced models, diet/nutrition induced diabetic animals, surgically induced models or pancreatectomy models, and non-obese models. Large animals or non-rodent models like porcine (pig), canine (dog), nonhuman primate, and Zebrafish models are also outlined. The in vitro models discussed are murine and human beta-cell lines and pancreatic islets, human stem cells, and organoid cultures. The other enzymatic in vitro tests to assess diabetes include assay of amylase inhibition and inhibition of α-glucosidase activity.
PubMed: 38837635
DOI: 10.1002/ame2.12442 -
International Journal of Biological... May 2024Cold as a common environmental stress, causes increased heat production, accelerated metabolism and even affects its production performance. How to improve the...
BACKGROUND
Cold as a common environmental stress, causes increased heat production, accelerated metabolism and even affects its production performance. How to improve the adaptability of the animal organism to cold has been an urgent problem. As a key hub of lipid metabolism, the liver can regulate lipid metabolism to maintain energy balance, and O-GlcNAcylation is a kind of important PTMs, which participates in a variety of signaling and mechanism regulation, and at the same time, is very sensitive to changes in stress and nutritional levels, and is the body's "stress receptors" and "nutrient receptors". Therefore, the aim of this experiment was to investigate the effect of cold-induced O-GlcNAcylation on hepatic lipid metabolism, and to explore the potential connection between O-GlcNAcylation and hepatic lipid metabolism.
METHODS
To investigate the loss of O-linked N-acetylglucosamine (O-GlcNAc) transferase (OGT) and the precise impacts of additional cold-induced circumstances on liver mass, shape, and metabolic profile, C57 mice were used as an animal model. Using the protein interactions approach, the mechanism of O-GlcNAcylation, as well as the degradation pathway of acyl-Coenzyme A oxidase 1 (ACOX1), were clarified. Additional in vitro analyses of oleic acid (OA) and OGT inhibitor tetraoxan (Alloxan) (Sigma, 2244-11-3) on lipid breakdown in AML-12 cells.
RESULTS
In C57BL/6 mice, deletion of O-GlcNAcylation disrupted lipid metabolism, caused hepatic edema and fibrosis, and altered mitochondrial apoptosis. This group of modifications was made worse by cold induction. The accumulation of medium- and long-chain fatty acids is a hallmark of lipolysis, which is accelerated by the deletion of O-GlcNAcylation, whereas lipid synthesis is slowed down. The association between ACOX1 and OGT at the K48 gene precludes ubiquitinated degradation.
Topics: Animals; Male; Mice; Fatty Acids; Lipid Metabolism; Liver; Mice, Inbred C57BL; N-Acetylglucosaminyltransferases; Proteolysis; Ubiquitination; Acyl-CoA Oxidase; Acetylglucosamine
PubMed: 38547945
DOI: 10.1016/j.ijbiomac.2024.131151 -
Metabolism Open Mar 2024Diabetes mellitus (DM) is one of the leading worldwide public health problems. It is characterized by hyperglycemia which induces oxidative stress and inflammation, both...
Diabetes mellitus (DM) is one of the leading worldwide public health problems. It is characterized by hyperglycemia which induces oxidative stress and inflammation, both involved in the pathogenesis of diabetes. We previously showed that (BD) and (HS) extracts reduced hyperglycemia and hyperlipidemia in alloxan-induced diabetic rats. In the present study, we evaluated the antioxidant and anti-inflammatory activities of both plants in alloxan-induced diabetic rats. Two sets of experiments were conducted in male Wistar rats subjected to a single intraperitoneal injection of alloxan monohydrate (150 mg/kg, b. w.). Then, diabetic rats were daily administered with either BD (1st set of experiments) or HS (2nd set of experiments) at 100, 200, and 400 mg/kg orally for 21 consecutive days. Glibenclamide (10 mg/kg) was also administered as a reference drug. At the end of the study, the animals were anesthetized, and blood samples were collected from each animal. Then, oxidative stress and inflammatory biomarkers in the serum were determined. We found that treatment with BD and HS significantly reduced malondialdehyde (MDA) and enhanced the levels of reduced glutathione (GSH), superoxide dismutase (SOD), and catalase (CAT). These extracts also significantly decreased the inflammatory markers tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and interleukin-1 beta (IL-1β). From the results obtained, it can therefore be concluded that BD and HS have the potential to being developed as natural sources of antioxidant and anti-inflammatory agents that can be used for the prevention or treatment of DM.
PubMed: 38455229
DOI: 10.1016/j.metop.2024.100278 -
Research in Veterinary Science Aug 2023Endothelial dysfunction is an early complication of diabetes and it is related to both micro- and macroangiopathies. In addition, >70% of diabetic patients develop...
Endothelial dysfunction is an early complication of diabetes and it is related to both micro- and macroangiopathies. In addition, >70% of diabetic patients develop autonomic neuropathies. Increased oxidative stress has a major role in the development of both nitrergic and endothelial dysfunction. The aim of this work is to evaluate whether rutin, a potent antioxidant, could ameliorate nitrergic and/or endothelial dysfunction in diabetic animals. Primary and secondary treatment protocols with rutin were investigated on rat aortic rings and the mesenteric arteriolar bed, and on rabbit aortic rings and corpora cavernosa (RbCC) from both euglycemic and alloxan-diabetic animals. Acetylcholine endothelium-dependent and sodium nitroprusside endothelium-independent relaxations were compared in tissues from euglycemic or diabetic animals. Electrical field stimulation (EFS)-induced relaxation was performed only in the RbCC. Endothelial-dependent relaxations were blunted by 40% in vessels and neuronal relaxation was blunted by 50% in RbCC taken from diabetic animals when compared to euglycemic animals. Pre-treatment with rutin restored both neuronal and endothelial dependent relaxations in diabetic animals towards the values achieved in control euglycemic tissues. Rutin was able to ameliorate both endothelial dysfunction and nitrergic neuropathy in animal experimental models. Rutin could be a lead compound in the primary or secondary preventive ancillary treatment of endothelial and nitrergic dysfunction in the course of diabetes.
Topics: Male; Rats; Animals; Rabbits; Rutin; Penis; Nitroprusside; Acetylcholine; Endothelium, Vascular; Diabetes Mellitus; Nitric Oxide
PubMed: 37406575
DOI: 10.1016/j.rvsc.2023.06.020 -
Endocrinology May 2024Alloxan-induced diabetic rats present with hypothyroidism. When treated with triiodothyronine (T3), glycemia and proinflammatory cytokine expression are downregulated,...
Alloxan-induced diabetic rats present with hypothyroidism. When treated with triiodothyronine (T3), glycemia and proinflammatory cytokine expression are downregulated, improving insulin sensitivity. The effectiveness of associating T3 with insulin (replacement dose [6 U] and [3 U]) in controlling glycemia was investigated in this experimental model. Male Wistar rats were made diabetic by alloxan injection and sorted into groups treated or not with insulin (3 or 6 U) associated or not with T3 (1.5 µg 100 g-1 BW) for 28 days. Nondiabetic rats constituted the control group. Fasting glycemia, glucose decay rate, and thyrotropin (TSH) were measured in the blood/serum of all animals. Immunoblotting was used to assess total GLUT4 expression in skeletal muscles and epididymal white adipose tissue. Cytokine and nuclear factor-κB (NF-κB) expression were measured in these tissues and liver. Diabetic rats presented with increased fasting glycemia, inflammatory cytokines, and NF-κB expression, TSH levels, and insulin resistance. In diabetic rats treated with T3 and/or insulin, these parameters were decreased, whereas GLUT4 and anti-inflammatory cytokine expression were increased. T3 combined with 3-U insulin restored the parameters to values of the control group and was more effective at controlling glycemia than 6-U insulin. Thus, a combination of T3 and insulin might represent a promising strategy for diabetes management since it reduces the insulin requirement by half and improves glycemic control of diabetic rats, which could postpone insulin resistance that develops with chronic insulin administration. These findings open a perspective for using thyroid analogues that provide tissue-specific effects, which might result in a potentially more effective treatment of diabetes.
Topics: Animals; Male; Diabetes Mellitus, Experimental; Triiodothyronine; Rats, Wistar; Rats; Insulin; Glucose Transporter Type 4; Blood Glucose; NF-kappa B; Insulin Resistance; Alloxan; Muscle, Skeletal; Thyrotropin; Cytokines; Hypoglycemic Agents
PubMed: 38862394
DOI: 10.1210/endocr/bqae066 -
Journal of Ethnopharmacology Jan 2024Globally, 537 million individuals are estimated to have diabetes. The traditional use of herbs for ameliorating diabetes symptoms is a common practice in Pakistan and...
ETHNOPHARMACOLOGICAL RELEVANCE
Globally, 537 million individuals are estimated to have diabetes. The traditional use of herbs for ameliorating diabetes symptoms is a common practice in Pakistan and use of Loranthus pulverulentus Wall (L. pulverulentus) by local people in Azad Jammu and Kashmir has been reported.
AIM OF THE STUDY
In the present study, the antidiabetic potential of standardized n-butanol fraction of leaves of L. pulverulentus Wall, which is a parasite of Dalbergia sisso Roxb was assessed in both alloxan (ALX) and streptozotocin (STZ) diabetic animal models.
MATERIALS AND METHODS
Chemical characterization of BF was performed using HPLC, GCMS and UHPLC-MS. The effect of the fraction (250 mg/kg) on insulin, plasma free fatty acids, L-lactate, pyruvate, MDA, HbA1c and glycogen levels in ALX and STZ animal models was determined. Liver and renal profiles were analyzed in the STZ model. Toxicological studies were performed by hemolytic, Ames mutagenicity, DNA protection, and thrombolytic assays. Histopathological analysis of the pancreas, liver, and kidney was performed.
RESULTS
BF demonstrated highly significant (p < 0.001) antidiabetic potential in both diabetic models. BF significantly (p < 0.05) improved OGTT results in alloxanized diabetic mice and blocked the absorption of glucose from the gut. A significant (p < 0.001) increase in insulin levels and glycogen content in liver tissue and a decrease in plasma FFA, MDA, HbA1c, L-lactate, and pyruvate levels in STZ-diabetic mice were recorded. GC-MS and chromatographic analysis showed the presence of catechin, eugenol, longifolene, caryophyllene, Ar-tumerone and Geranyl-alpha-terpinene. Various metabolites with antidiabetic potential, including 4-hydroxycinnamyl alcohol 4-D-glucoside, zingerone glucoside, trans-trismethoxy resveratrol-d4, epigallocatechin 3-O-cinnamate, and β-glucogallin, were identified using UHPLC-MS. Animals treated with BF showed marked improvements in cellular structures of the pancreas, liver and kidneys. This fraction is non-mutagenic and protects the DNA.
CONCLUSION
The experimental fraction contained potential antidiabetic bioactive compounds responsible for alleviating diabetes-associated biochemical dysregulation. The fraction increased insulin levels and enhanced glycogen storage in muscles and the liver. It blocked glucose absorption from the intestine and substantially decreased HbA1c, lactate, pyruvate, free fatty acids, lipid, liver and kidney damage. Therefore, the use of BF for the treatment of type-2 diabetes may be beneficial.
Topics: Mice; Animals; Hypoglycemic Agents; 1-Butanol; Glycated Hemoglobin; Diabetes Mellitus, Experimental; Butanols; Fatty Acids, Nonesterified; Plant Extracts; Blood Glucose; Insulin; Liver; Glycogen; Glucosides; Pyruvates; Streptozocin
PubMed: 37495027
DOI: 10.1016/j.jep.2023.116963 -
Current Pharmaceutical Biotechnology Aug 2023The current study aimed to develop an economic plant-based therapeutic agent to improve the treatment strategies for diseases at the nano-scale because Cancer and...
BACKGROUND
The current study aimed to develop an economic plant-based therapeutic agent to improve the treatment strategies for diseases at the nano-scale because Cancer and Diabetes mellitus are major concerns in developing countries. Therefore, in vitro and in vivo anti-diabetic and anti-cancerous activities of Trillium govanianum conjugated silver nanoparticles were assessed.
METHODS
In the current study synthesis of silver nanoparticles using Trillium govanianum and characterization were done using a scanning electron microscope, UV-visible spectrophotometer, and FTIR analysis. The in vitro and in vivo anti-diabetic and anti-cancerous potential (200 mg/kg and 400 mg/kg) were carried out.
RESULTS
It was discovered that Balb/c mice did not show any major alterations during observation of acute oral toxicity when administered orally both TGaqu (1000 mg/kg) and TGAgNPs (1000 mg/kg), and results revealed that 1000 mg/kg is not lethal dose as did not find any abnormalities in epidermal and dermal layers when exposed to TGAgNPs. In vitro studies showed that TGAgNPs could not only inhibit alpha-glucosidase and protein kinases but were also potent against the brine shrimp. Though, a significant reduction in blood glucose levels and significant anti-cancerous effects was recorded when alloxan-treated and CCl4-induced mice were treated with TGAgNPs and TGaqu.
CONCLUSION
Both in vivo and in vitro studies revealed that TGaqu and TGAgNPs are not toxic at 200 mg/kg, 400 mg/kg, and 1000 mg/kg doses and possess strong anti-diabetic and anti-cancerous effects due to the presence of phyto-constituents. Further, suggesting that green synthesized silver nanoparticles could be used in pharmaceutical industries to develop potent therapeutic agents.
PubMed: 37594092
DOI: 10.2174/1389201024666230818124025 -
Biomedicine & Pharmacotherapy =... Jul 2023Diabetic retinopathy (DRET) triggers vision loss in adults, however, little therapeutic options are existing. Memantine is an anti-Alzheimer drug that antagonizes the...
Diabetic retinopathy (DRET) triggers vision loss in adults, however, little therapeutic options are existing. Memantine is an anti-Alzheimer drug that antagonizes the activity of glutamate at N-methyl-D-aspartate (NMDA) receptors. Glutamate and thioredoxin-interacting protein (TXNIP) are known to be overexpressed in diabetic retinas and can produce activation of NOD-like receptor protein 3 (NLRP3) with subsequent secretion of interlukin-1β. This study repurposed memantine for its neuroprotective effect in experimental DRET and tested its impact on ROS/TXNIP/NLRP3. In addition, KEGG pathway database and STRING database identified the protein-protein interaction between glutamate receptors and TXNIP/NLRP3. Male Swiss albino mice received alloxan (180 mg/kg) to induce DRET. After 9 weeks, we divided the mice into groups: (a) saline, (ii) DRET, (iii and iv) DRET + oral memantine (5 or 10 mg per kg) for 28 days. Then, mice were euthanized, and eyeballs were removed. Retinal samples were utilized for biochemical, histopathological, and electron microscopy studies. Retinal levels of glutamate, TXNIP, NLRP3 and interlukin-1β were estimated using ELISA technique as well as retinal malondialdehyde. Histopathological and ultrastructural examination demonstrated that oral memantine attenuated vacuolization and restored normal retinal cell layers. Moreover, memantine reduced TXNIP, NLRP3, interleukin-1β and MDA concentrations. These results provide evidence demonstrating memantine' efficacy in alleviating DRET via suppressing reactive oxygen species/TXNIP/NLRP3 signaling cascade. Therefore, memantine might serve as a potential therapy for retinopathy after adequate clinical research.
Topics: Mice; Male; Animals; NLR Family, Pyrin Domain-Containing 3 Protein; Diabetic Retinopathy; Inflammasomes; Reactive Oxygen Species; Memantine; NLR Proteins; Glutamates; Thioredoxins; Diabetes Mellitus; Carrier Proteins
PubMed: 37116352
DOI: 10.1016/j.biopha.2023.114772