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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 -
Biomedicine & Pharmacotherapy =... Jul 2024Diabetes and derived complications, especially diabetic nephropathy and neuropathy annually cause great morbimortality worldwide. 5-hydroxytryptamine (5-HT) acts as a...
Diabetes and derived complications, especially diabetic nephropathy and neuropathy annually cause great morbimortality worldwide. 5-hydroxytryptamine (5-HT) acts as a modulator of renal sympathetic input and vascular tone. In this line, 5-HT receptor blockade has been linked with reduced incidence and progression of diabetic microvascular alterations. In this work, we aimed to determine, in diabetic rats, whether 5-HT blockade ameliorates renal function and to characterize the serotonergic modulatory action on renal sympathetic neurotransmission. Diabetes was induced in male Wistar rats by alloxan administration (150 mg/kg, s.c.), and sarpogrelate (30 mg/kg·day, p.o.; 5-HT antagonist) was administered for 14 days (DM-S). Normoglycemic and diabetic (DM) animals were maintained as aged-matched controls. At 28th day, DM-S animals were anesthetized and prepared for the in situ autoperfusion of the kidney. Renal vasoconstrictor responses were induced electrically or by i.a. noradrenaline (NA) administration. The role of 5-HT and selective 5-HT agonist/antagonist were studied on these renal vasopressor responses. Sarpogrelate treatment decreased renal sympathetic-induced vasopressor responses, reduced renal hypertrophy and kidney damage markers increased in DM. Intraarterial 5-HT inhibited the sympathetic-induced renal vasoconstrictions, effect reproduced by 5-CT, AS-19, L-694,247 and LY 344864 (5-HT, 5-HT, 5-HT and 5-HT receptor agonists, respectively). Blocking 5-HT receptors completely abolished the 5-CT sympatho-inhibition. NA vasoconstrictions were not altered by any of the 5-HT agonists tested. Thus, in experimental diabetes, chronic sarpogrelate treatment reduces renal damage markers, kidney hypertrophy and renal sympathetic hyperactivity and modifies serotonergic modulation of renal sympathetic neurotransmission, causing a sympatho-inhibition by prejunctional 5-HT and 5-HT activation.
Topics: Animals; Succinates; Male; Diabetes Mellitus, Experimental; Rats, Wistar; Kidney; Sympathetic Nervous System; Rats; Serotonin 5-HT2 Receptor Antagonists; Serotonin; Diabetic Nephropathies; Vasoconstriction
PubMed: 38820974
DOI: 10.1016/j.biopha.2024.116814 -
Frontiers in Chemistry 2023The present research aimed to fractionate L. (XSL) foliage phenolics into a set of solvents and evaluate their antioxidant potential and anti-diabetic activity...
The present research aimed to fractionate L. (XSL) foliage phenolics into a set of solvents and evaluate their antioxidant potential and anti-diabetic activity against Alloxan monohydrate-induced diabetic mice. For this purpose, XSL foliage was fractionated into petroleum ether, ethyl acetate, ethanol, and water orbital type shaking and tested for the presence of phenolics, and their antioxidant and antidiabetic potential. The results revealed that the ethyl acetate fraction of XSL foliage contained the highest amount of total phenolics 95.25 mg GAE/g of extract, followed by ethanol (65.14 mg GAE/g), petroleum ether (25.12 mg GAE/g), water (12.20 mg GAE/g), and XSL powder (69.13 mg GAE/g). At the end of treatment time (day 18 of oral administration of 400 mg/kg body weight of mice), the ethyl acetate fraction significantly ( ≤ 0.05) lowered blood glucose level (353 ± 10.6 to 220 ± 25.5 mg/dL) which might due to the elevated level of phenolic compounds in this fraction. Overall, it can be speculated that ethyl acetate and ethanol may work efficiently for the enrichment of XSL phenolic without compromising their antidiabetic potential.
PubMed: 38053673
DOI: 10.3389/fchem.2023.1279729 -
Medicina (Kaunas, Lithuania) Jul 2023: Worldwide, approximately 500 million people suffer from diabetes and at least 50% of these people develop neuropathy. Currently, therapeutic strategies for reducing...
: Worldwide, approximately 500 million people suffer from diabetes and at least 50% of these people develop neuropathy. Currently, therapeutic strategies for reducing diabetic neuropathy (DN)-associated pain are limited and have several side effects. The purpose of the study was to evaluate the antihyperalgesic action of different sildenafil (phosphodiesterase-5 inhibitor) and metformin (antihyperglycemic agent) combinations in alloxan-induced DN. : The study included 100 diabetic mice and 20 non-diabetic mice that were subjected to hot and cold stimulus tests. Furthermore, we determined the influence of this combination on TNF-α, IL-6 and nitrites levels in brain and liver tissues. : In both the hot-plate and tail withdrawal test, all sildenafil-metformin combinations administered in our study showed a significant increase in pain reaction latencies when compared to the diabetic control group. Furthermore, all combinations decreased blood glucose levels due to the hypoglycemic effect of metformin. Additionally, changes in nitrite levels and pro-inflammatory cytokines (TNF-α and IL-6) were observed after 14 days of treatment with different sildenafil-metformin combinations. : The combination of these two substances increased the pain reaction latency of diabetic animals in a dose-dependent manner. Moreover, all sildenafil-metformin combinations significantly reduced the concentration of nitrites in the brain and liver, which are final products formed under the action of iNOS.
Topics: Mice; Animals; Diabetic Neuropathies; Hyperalgesia; Metformin; Sildenafil Citrate; Interleukin-6; Nitrites; Tumor Necrosis Factor-alpha; Pain; Hypoglycemic Agents; Biomarkers; Diabetes Mellitus
PubMed: 37629665
DOI: 10.3390/medicina59081375 -
Scientific Reports Feb 2024Zebrafish have been utilized for many years as a model animal for pharmacological studies on diabetes and obesity. High-fat diet (HFD), streptozotocin and alloxan...
Zebrafish have been utilized for many years as a model animal for pharmacological studies on diabetes and obesity. High-fat diet (HFD), streptozotocin and alloxan injection, and glucose immersion have all been used to induce diabetes and obesity in zebrafish. Currently, studies commonly used both male and female zebrafish, which may influence the outcomes since male and female zebrafish are biologically different. This study was designed to investigate the difference between the metabolites of male and female diabetic zebrafish, using limonene - a natural product which has shown several promising results in vitro and in vivo in treating diabetes and obesity-and provide new insights into how endogenous metabolites change following limonene treatment. Using HFD-fed male and female zebrafish, we were able to develop an animal model of T2D and identify several endogenous metabolites that might be used as diagnostic biomarkers for diabetes. The endogenous metabolites in males and females were different, even though both genders had high blood glucose levels and a high BMI. Treatment with limonene prevented high blood glucose levels and improved in diabesity zebrafish by limonene, through reversal of the metabolic changes caused by HFD in both genders. In addition, limonene was able to reverse the elevated expression of AKT during HFD.
Topics: Animals; Female; Male; Hypoglycemic Agents; Limonene; Zebrafish; Blood Glucose; Proton Magnetic Resonance Spectroscopy; Obesity; Diet, High-Fat; Hyperglycemia; Diabetes Mellitus
PubMed: 38360784
DOI: 10.1038/s41598-023-45608-z -
Molecules (Basel, Switzerland) Sep 2023This study aimed to investigate the phenolic and antioxidant properties of Egyptian leaves extract (SOE) while comparing the antihyperglycemic efficacy of SOE with that...
This study aimed to investigate the phenolic and antioxidant properties of Egyptian leaves extract (SOE) while comparing the antihyperglycemic efficacy of SOE with that of conventional medicines (glibenclamide) in vivo as a substitution for insulin-deficient patients. Total phenolic (TPC) and flavonoid contents (TFC) in SOE contributed around 127.66 ± 0.56 mg GAE/gm as gallic acid equivalent (GAE) and 74.80 ± 0.55 mg QE/gm as quercetin equivalent (QE). SOE also showed significant DPPH scavenging activity at 43.46%. The presence of five phenolic and six flavonoid compounds in SOE was discovered by HPLC analysis. For the in vivo assay, 42 rats were distributed into six groups (7 Wister albino rats each). The standard control group was fed a basal diet. While the 35 rats were induced with a single dose of 100 mg kg body weight (b.w.) alloxan, then treated orally with glibenclamide (GLI) at 10 mg kg, 100, 200, and 300 mg kg SOE (positive control group) for 56 days of routine gastric oral gavages and compared to the effects of GLI, the treatment of SOE 200 and 300 mg kg in diabetic rats for two months dramatically decreased blood glucose, total lipid, total cholesterol, and low-density lipoprotein cholesterol (LDLC) while boosting high-density lipoprotein cholesterol (HDLC) levels and improving liver and kidney functions. The histological assay revealed that the SOE 300 mg kg treatment significantly improved the pancreas tissues, implying the potential application of Egyptian SOE as a diabetes treatment.
Topics: Animals; Rats; Rats, Wistar; Hypoglycemic Agents; Antioxidants; Sonchus; Glyburide; Diabetes Mellitus, Experimental; Egypt; Gallic Acid; Quercetin; Cholesterol, LDL; Flavonoids
PubMed: 37687218
DOI: 10.3390/molecules28176389 -
Journal of Advanced Veterinary and... Dec 2023Andaliman () is a potent medicinal plant in Asia. This present study aimed to reveal the effectivity of Andaliman fruit extract in alleviating hyperglycemia, sensory and...
OBJECTIVE
Andaliman () is a potent medicinal plant in Asia. This present study aimed to reveal the effectivity of Andaliman fruit extract in alleviating hyperglycemia, sensory and motoric balance disorders, histopathology of the cerebellum, and tissue oxidative stress in diabetic mice induced by alloxan.
MATERIALS AND METHODS
Diabetes induction was performed by intraperitoneally injecting alloxan monohydrate [200 mg/kg body weight (BW)]. Subsequently, the mice were treated daily with an ethanolic extract of Andaliman fruit (0, 150, 300, 450 mg/kg BW per oral) for 28 days, followed by measurements of blood glucose, paw sensitivity, motoric balance, histopathology of the cerebellum, and malondialdehyde (MDA) levels. Moreover, the phytochemical constituents of the extract were elucidated by liquid chromatography.
RESULTS
Higher doses of Andaliman fruit extract could significantly attenuate the elevation of random and fasting blood glucose ( < 0.05) and improve paw sensitivity responses ( < 0.05) and motoric balances ( < 0.05) in diabetic mice. Moreover, Andaliman fruit extract could significantly attenuate the degeneration of cerebellar Purkinje cells ( < 0.05) and suppress MDA levels in the blood ( < 0.05) while blunting the MDA in the brain tissue ( < 0.05). Phytochemical screening revealed 39 compounds in the Andaliman extract belonging to the groups of alkaloids (26 compounds), flavonoids (12 compounds), and terpenoids (1 compound).
CONCLUSION
The ethanolic extract of Andaliman fruit is capable of ameliorating diabetic neuropathy, motor balance disorders, and Purkinje cell degeneration while also reducing oxidative stress in the peripheral system. Hence, Andaliman extract is a promising candidate for formulation as an herbal remedy against the detrimental outcomes of diabetes mellitus.
PubMed: 38370902
DOI: 10.5455/javar.2023.j716 -
Advances in Wound Care Mar 2024Diabetes mellitus (DM) affects over 422 million people globally. Patients with DM are subject to a myriad of complications, of which diabetic foot ulcers (DFUs) are the...
Diabetes mellitus (DM) affects over 422 million people globally. Patients with DM are subject to a myriad of complications, of which diabetic foot ulcers (DFUs) are the most common with ∼25% chance of developing these wounds throughout their lifetime. Currently there are no therapeutic RNAs approved for use in DFUs. Use of dressings containing novel layer-by-layer (LbL)-formulated therapeutic RNAs that inhibit PHD2 and miR-210 can significantly improve diabetic wound healing. These dressings provide sustained release of therapeutic RNAs to the wounds locally without systemic side effects. Diabetic foot wounds are difficult to heal and often result in significant patient morbidity and mortality. We used the diabetic neuroischemic rabbit model of impaired wound healing. Diabetes was induced in the rabbits with alloxan, and neuroischemia was induced by ligating the central neurovascular bundle of each ear. Four 6-mm full-thickness wounds were created on each ear. A LbL technique was used to conformally coat the wound dressings with chemically modified RNAs, including an antisense oligonucleotide (antimiR) targeting microRNA-210 (miR-210), an short synthetic hairpin RNA (sshRNA) targeting PHD2, or both. Wound healing was improved by the antimiR-210 but not the PHD2-sshRNA. Specific knockdown of miR-210 in tissue as measured by RT-qPCR was ∼8 Ct greater than nonspecific controls, and this apparent level of knockdown (>99%) suggests that delivery to the tissue is highly efficient at the administered dose. Healing of ischemic/neuropathic wounds in diabetic rabbits was accelerated upon inhibition of miR-210 by LbL delivery to the wound bed. miR-210 inhibition was achieved using a chemically modified antisense RNA.
PubMed: 38183631
DOI: 10.1089/wound.2023.0056 -
Heliyon Sep 2023Diabetes mellitus is a commonly occurring metabolic disorder accompanied by high morbidity and alarming mortality. Besides various available therapies, induction of...
BACKGROUND
Diabetes mellitus is a commonly occurring metabolic disorder accompanied by high morbidity and alarming mortality. Besides various available therapies, induction of pancreatic regeneration has emerged as a promising strategy for alleviating the damaging effect of diabetes. Honey, a potent antioxidative and anti-inflammatory agent, has been reported in the literature archive to exhibit favourable results in the regeneration process of several organ systems.
DESIGN
The current research work was intended to explore the potential role of manuka honey in pancreatic regeneration in alloxan-induced diabetic rats by accessing the pancreatic histology and levels of relevant transcription factors, including MAFA, PDX-1, INS-1, INS-2, NEUROG3, NKX6-1, and NEUROD. An equal number of rats were allocated to all four experimental groups: normal, negative control, positive control, and treatment group. Diabetes was induced in all groups except normal through a single intraperitoneal dose of alloxan monohydrate. No subsequent treatment was given to the negative control group, while the positive control and treatment groups were supplemented with metformin (150 mg/kg/day) and manuka honey (3 g/kg/day), respectively.
RESULTS
Statistical comparison of glucose and insulin levels, oxidative stress indicators, changes in the architecture of pancreatic islets, and expression levels of regeneration-associated transcription factors advocated the potential role of manuka honey in ameliorating the alloxan-induced hyperglycaemia, hyperinsulinemia, oxidative stress, and necrotic changes in islets along with significant upregulation of relevant transcription factors.
CONCLUSION
This suggests to us the auspicious role of antioxidants in honey in pancreatic regeneration and advocates the favourable role of manuka honey in combating diabetes mellitus.
PubMed: 37809953
DOI: 10.1016/j.heliyon.2023.e20017 -
Brazilian Journal of Biology = Revista... 2023The study was conducted to examine the antioxidant activity and evaluate the protective effects of the date seeds powder kentichi against alloxan-induced damage in the...
The study was conducted to examine the antioxidant activity and evaluate the protective effects of the date seeds powder kentichi against alloxan-induced damage in the liver, kidney, and pancreas in diabetic's rats. Group 1: control group, that did not receive any treatment, Group 2: alloxan was injected intraperitoneally (120 mg/kg body weight) for two days (Diab), Group 3: treated only by date seeds powder added in the diet (300 g/kg) for 6 weeks (DSPK), Group 4: alloxan-diabetic rats treated with date seeds powder (300 g/kg) (DSPK + Diab). Estimations of biochemical parameters in blood were determined. TBARS, SOD, CAT, and GPx activities were determined. A histopathological study was done by immersing pieces of both organs in a fixative solution followed by paraffin hematoxylin-eosin staining. In addition, the antioxidant activities of DSPK were evaluated by DPPH radical scavenging activity, reducing power, and ABTS free radical scavenging. The results revealed that date seeds significantly decreased serum levels of glucose, cholesterol, triglycerides, urea, creatinine, T-protein, ALP, D-bili and T-bili levels. In addition, superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) activities that had been reduced in liver, kidney, and pancreas of the treated group were restored by DSPK treatments and, therefore, the lipid peroxidation level was reduced in the liver, kidney and pancreas tissue compared to the control group. Additionally, the histological structure in these organs was restored after treatment with date seeds powder.
Topics: Rats; Animals; Antioxidants; Phoeniceae; Alloxan; Oxidative Stress; Diabetes Mellitus, Experimental; Rats, Wistar; Powders; Plant Extracts; Superoxide Dismutase; Seeds; Lipid Peroxidation
PubMed: 38126632
DOI: 10.1590/1519-6984.274405