Induction Of Diabetes Research Articles

Myocardial and Skeletal Muscle Microvascular Dysfunction Manifests Prior to Diabetic Cardiomyopathy: Sex-Dependent Differences

Introduction: Microvascular dysfunction is a recognized sign of disease in heart failure progression. Blood vessels exhibit abnormal vasoreactivity in early stage, subsequently deteriorating to rarefaction and reduced perfusion. In managing heart failure patients, where diagnosis is typically possible only when the hypertrophic heart is irreversibly damaged, earlier diagnosis is key to improving management. In this study, we apply a blood-pool MRI method for assessing vasomodulation to investigate if it can sensitively detect abnormal leg muscle vasoreactivity posited to manifest before myocardial mvD. Methods: Male and female Sprague-Dawley rats were maintained on a high-fat, high-sugar diet or a control diet for 6 months after the induction of diabetes. Beginning at month 1 or 2 post-induction and every 2 months thereafter, rats underwent blood-pool MRI to assess vasoreactivity in the heart or skeletal muscle, respectively. Ablavar, a T1-reducing blood-pool contrast agent, was administered and the T1 relaxation time dynamically measured as animals breathed in mild CO2 levels to modulate vessels and elicit a vasodilatory response. CO2 levels were set at 5% for skeletal muscle and 10% for cardiac muscle, and the gas was administered for 10 minutes. At the final timepoint, invasive laser Doppler perfusion measurements in leg muscle were recorded to verify MRI results. Results/Discussion: In this study, we provide the first demonstration that both skeletal muscle and myocardial microvascular vasoreactivity is altered in a non-obese rodent model of type II diabetes, prior to the development of heart failure symptoms. In male rats, the normally unresponsive heart to 10% CO2 reveals a pro-vasoconstriction response beginning at 5 months post-diabetes. Abnormal leg skeletal muscle vasoreactivity appeared even earlier, at 2 months: the usual vasodilatory response to 5% CO2 is interrupted with periods of vasoconstriction in diseased rats. In female rats, differences were observed between healthy and diseased animals only within the first two months post-diabetes and not later. In the heart, vasodilation to 10% CO2 seen in healthy animals was abolished in diabetes. In skeletal muscle, 5% CO2 was suboptimal in inducing reproducible vasoreactivity, but young diabetic females responded by vasodilation only. Conclusion: Abnormal vasoreactivity presents earlier than overt structural and functional cardiac changes in both sexes in HFpEF and can be detected using blood-pool MRI in leg skeletal muscle before the myocardium. Our non-invasive MRI technology sets the foundation for a paradigm shift in diagnosing mvD during the early stages of HFpEF, opening the door for early intervention. This work was supported by the Canadian Institutes of Health Research, Natural Sciences and Engineering Research Council of Canada, Canada Foundation for Innovation/Ontario Research Fund, Dean’s Spark Professorship, Medicine by Design Pivotal Experiment Fund [to H.L.M.C.]; Ted Rogers Centre for Heart Research PhD Education Fund, Scintica Instrumentation Inc [to S.L.]. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Capturing of neurotoxins causing diabetes stress and nervous breakdown in the aqueous medium by naphthazarin esters.

The fear of an increase in blood sugar can be very traumatic. Being diabetic either type I or type II leads to a disorder called diabetes distress having traits of stress, depression, and anxiety. Among risk factors of diabetes mellitus heavy and trace metal toxicity emerges as new risk factors reported in many studies. In this study we target toxic metals, viz., Ni2+, Zn2+, and Cu2+, involved in the pathogenesis of diabetes and diabetic stress with naphthazarin esters. The compounds C1-C3 isolated from the leaves and roots of Arnebia guttata were tested for their metal-binding ability in an aqueous medium in UV-Visible and nuclear magnetic resonance (NMR) studies. These probes are well-known naphthoquinones present in the Arnebia species. In the UV-Visible titrations of compounds C1-C3 with Na2+, K2+, Zn2+, Ca2+, Cu2+, Mg2+, Co2+, and Ni2+ ions, significant binding was observed with Ni2+, Cu2+, and Zn2+ ions in MeOH/H2O. There occurs a beautiful formation of red-shifted bands between the 520 to 620 nm range with a synergistic increase in absorbance. Also, the disappearance of proton peaks in the 1H NMR spectrum on addition of metal ions confirmed binding. Compounds C1-C3 isolated from A. guttata came out as potent Ni2+, Zn2+, and Cu2+ sensors that are reportedly involved in islet function and induction of diabetes.

Synergistic Effect of Naringin and Glimepiride in Streptozotocin-induced Diabetic Rats.

Evaluation of the synergistic effect of Naringin and Glimepiride in streptozotocin (STZ)-induced diabetic rats. Wistar rats were chosen and divided into five groups (n=6). STZ was used for the induction of diabetes. The combination of naringin and glimepiride was administered to diabetic rats. The changes in fasting blood sugar, body weight, Hb, HbA1c, and creatinine were evaluated, and urine was collected and the volume was observed. The lipid profiles like TC, HDL, LDL, and TG were measured. The biochemical parameters SGOT, SGPT, and ALP were analysed. Besides, endogenous antioxidant parameters like SOD, GSH, and catalase were also assessed. Lastly, the histopathological study of the beta cells in islets of the pancreas, glomerulus, and tubules of kidney and liver cells was conducted in all groups. The result shows significant reduction (p<0.001) of blood sugar in the naringin and glimepiride-treated group when compared with the control group (diabetes). Additionally, the combination of Naringin (100 mg/kg) and Glimepiride (0.1 mg/kg) significantly restores the creatinine levels and urine volumes, SGOT, SGPT, and ALP when compared to a single dose of administration. Further, the abnormal lipid profile levels (TC, LDL, TG, and HDL), and endogenous antioxidant enzymes (SOD, GSH, catalase) in diabetic control rats were restored to normal levels in a significant manner. The histopathological result reveals significant alterations, including hypertrophy of islets and mild degeneration, renal necrosis, and inflammation of hepatocytes. A synergistic effect of Naringin and glimepiride was observed during the estimation of various biochemical parameters like body weight, fasting blood sugar, creatinine, urine level, TG, total cholesterol, SGOT, SGPT, ALP, Insulin, HbA1c, antioxidant parameters like SOD, GSH, and catalase in STZ-induced diabetic rats. Further, the combination of therapy improves the protective effect of the pancreas, kidney, and liver, suggesting a potential antidiabetic effect.

Efek Pemberian Ekstrak Daun Gelagah (Saccharum spontaneum L.) terhadap Diabetes Induksi Aloksan pada Tikus Putih (Rattus Norvegicus)

Saccharum spontaneum L. (Family: Poaceae) is a tall perennial grass with deep roots and rhizomes, capable of growing up to 3-4 meters in height, and is commonly found along water bodies or roadsides. This plant is widely distributed throughout the tropical regions of Asia, Africa, America, and Australia. Saccharum spontaneum L. is a tall, erect, perennial grass with feathery inflorescences, often growing in swampy areas. Its leaves and stems contain lignin, carbohydrates, proteins, and amino acids, while its roots and lower stems contain starch and polyphenolic compounds. This study aims to evaluate the effect of Saccharum spontaneum L. leaves extract on blood glucose levels in male white rats (Rattus norvegicus) induced with alloxan. The leaves extract was obtained through maceration using 96% ethanol solvent. Phytochemical screening results indicated that the leaves of Saccharum spontaneum L. contain alkaloids, flavonoids, saponins, tannins, and steroids/triterpenoids. The antidiabetic test was conducted using male Wistar rats. In this study, the Saccharum spontaneum L. leaves extract was administered in three different doses: group 4 received a dose of 100 mg/KgBW, group 5 received a dose of 200 mg/KgBW, and group 6 received a dose of 400 mg/KgBW. Additionally, there were control groups consisting of group 1 (normal), group 2 (negative control), and group 3 (positive control) which were given the drug glibenclamide 5 mg/60 kg. All doses were administered orally. Diabetes induction in the rats was performed using alloxan monohydrate at a dose of 100 mg/KgBW administered intraperitoneally. The results of the study showed that the greatest reduction in blood glucose levels occurred in group 6 with a dose of 400 mg/KgBW, which decreased blood glucose levels by 71.78% at the 180th minute. Group 5 showed a reduction of 55.80% and group 4 showed a reduction of 51.91% at the 180th minute. Group 3, which was given glibenclamide, showed a reduction in blood glucose levels of 71.14% at the 180th minute. These results indicate that the highest dose of Saccharum spontaneum L. leaves extract (400 mg/KgBW) had the most significant effect in lowering blood glucose levels in male Wistar rats induced with alloxan monohydrate

Induction of diabetes by Tacrolimus in a phenotypic model of obesity and metabolic syndrome.

The pathogenesis of Post-Transplant Diabetes Mellitus (PTDM) is complex and multifactorial and it resembles that of Type-2 Diabetes Mellitus (T2DM). One risk factor specific to PTDM differentiates both entities: the use of immunosuppressive therapy. Specifically, Tacrolimus interacts with obesity and insulin resistance (IR) in accelerating the onset of PTDM. In a genotypic model of IR, the obese Zucker rats, Tacrolimus is highly diabetogenic by promoting the same changes in beta-cell already modified by IR. Nevertheless, genotypic animal models have their limitations and may not resemble the real pathophysiology of diabetes. In this study, we have evaluated the interaction between beta-cell damage and Tacrolimus in a non-genotypic animal model of obesity and metabolic syndrome. Sprague Dawley rats were fed a high-fat enriched diet during 45 days to induce obesity and metabolic dysregulation. On top of this established obesity, the administration of Tacrolimus (1mg/kg/day) during 15 days induced severe hyperglycaemia and changes in morphological and structural characteristics of the pancreas. Obese animals administered with Tacrolimus showed increased size of islets of Langerhans and reduced beta-cell proliferation without changes in apoptosis. There were also changes in beta-cell nuclear factors such as a decrease in nuclear expression of MafA and a nuclear overexpression of FoxO1A, PDX-1 and NeuroD1. These animals also showed increased levels of pancreatic insulin and glucagon. This model could be evidence of the relationship between the T2DM and PTDM physiopathology and, eventually, the model may be instrumental to study the pathogenesis of T2DM.

Effect of Eight Weeks of Endurance Training on Some Oxidant and Antioxidant Indicators of Testicular Tissue of Diabetic Rats with Acute Morphine Withdrawal Syndrome

Introduction: Diabetes along with morphine causes many metabolic damages in the testicles by causing oxidative stress. This study aimed to reduce the oxidative effects caused by diabetes and morphine on the fertility quality of men with the help of increasing moderate intensity aerobic exercise. Methods: 32 male Wistar rats were used in this experimental study. Mice were randomly divided into 4 groups of 8: diabetes control (D), morphine diabetes (D. M), diabetes + endurance training (D+ ET), diabetes + morphine endurance training (D. M+ ET). Then induction of diabetes and morphine was done. The training groups performed 8 weeks of endurance training protocol. At the end of the study, all mice were killed and their testis tissue was isolated. The oxidant and antioxidant indices of this study were measured. Data were analyzed by SPSS software version 16 using one-way ANOVA at a significant level of 0.05. Results: The results showed that the concentration of MDA in the diabetes group had a significant increase compared to other groups (P=0.001). However, increasing endurance training caused a significant decrease in the concentration of MDA (P=0. 001) and a significant increase in the amount of TAC, GPX and SOD (P=0. 001) in other groups compared to the diabetes group. Conclusion: The present research showed that increasing endurance training with moderate intensity caused a decrease in the oxidant index and an increase in the antioxidant index in the testicular tissue of diabetic rats with withdrawal syndrome. And this shows the reduction of infertility complications in mice.

Human umbilical cord-derived mesenchymal stromal cells improve myocardial fibrosis and restore miRNA-133a expression in diabetic cardiomyopathy

BackgroundDiabetic cardiomyopathy (DCM) is a serious health-threatening complication of diabetes mellitus characterized by myocardial fibrosis and abnormal cardiac function. Human umbilical cord mesenchymal stromal cells (hUC-MSCs) are a potential therapeutic tool for DCM and myocardial fibrosis via mechanisms such as the regulation of microRNA (miRNA) expression and inflammation. It remains unclear, however, whether hUC-MSC therapy has beneficial effects on cardiac function following different durations of diabetes and which mechanistic aspects of DCM are modulated by hUC-MSC administration at different stages of its development. This study aimed to investigate the therapeutic effects of intravenous administration of hUC-MSCs on DCM following different durations of hyperglycemia in an experimental male model of diabetes and to determine the effects on expression of candidate miRNAs, target mRNA and inflammatory mediators.MethodsA male mouse model of diabetes was induced by multiple low-dose streptozotocin injections. The effects on severity of DCM of intravenous injections of hUC-MSCs and saline two weeks previously were compared at 10 and 18 weeks after diabetes induction. At both time-points, biochemical assays, echocardiography, histopathology, polymerase chain reaction (PCR), immunohistochemistry and enzyme-linked immunosorbent assays (ELISA) were used to analyze blood glucose, body weight, cardiac structure and function, degree of myocardial fibrosis and expression of fibrosis-related mRNA, miRNA and inflammatory mediators.ResultsSaline-treated diabetic male mice had impaired cardiac function and increased cardiac fibrosis after 10 and 18 weeks of diabetes. At both time-points, cardiac dysfunction and fibrosis were improved in hUC-MSC-treated mice. Pro-fibrotic indicators (α-SMA, collagen I, collagen III, Smad3, Smad4) were reduced and anti-fibrotic mediators (FGF-1, miRNA-133a) were increased in hearts of diabetic animals receiving hUC-MSCs compared to saline. Increased blood levels of pro-inflammatory cytokines (IL-6, TNF, IL-1β) and increased cardiac expression of IL-6 were also observed in saline-treated mice and were reduced by hUC-MSCs at both time-points, but to a lesser degree at 18 weeks.ConclusionIntravenous injection of hUC-MSCs ameliorated key functional and structural features of DCM in male mice with diabetes of shorter and longer duration. Mechanistically, these effects were associated with restoration of intra-myocardial expression of miRNA-133a and its target mRNA COL1AI as well as suppression of systemic and localized inflammatory mediators.

N-acetylcysteine Protects Against Myocardial Ischemia–Reperfusion Injury Through Anti-ferroptosis in Type 1 Diabetic Mice

The hearts of subjects with diabetes are vulnerable to ischemia–reperfusion injury (IRI). In contrast, experimentally rodent hearts have been shown to be more resistant to IRI at the very early stages of diabetes induction than the heart of the non-diabetic control mice, and the mechanism is largely unclear. Ferroptosis has recently been shown to play an important role in myocardial IRI including that in diabetes, while the specific mechanisms are still unclear. Non-diabetic control (NC) and streptozotocin-induced diabetic (DM) mice were treated with the antioxidant N-acetylcysteine (NAC) in drinking water for 4 week starting at 1 week after diabetes induction. Mice were subjected to myocardial IRI induced by occluding the coronary artery for 30 min followed by 2 h of reperfusion, subsequently at 1, 2, and 5 week of diabetes induction. The post-ischemic myocardial infarct size in the DM mice was smaller than that in NC mice at 1 week of diabetes but greater than that in the NC mice at 2 and 5 week of diabetes, which were associated with a significant increase of ferroptosis at 2 and 5 week but a significant reduction of ferroptosis at 1 week of diabetes. NAC significantly attenuated post-ischemic ferroptosis as well as oxidative stress and reduced infarct size at 2 and 5 week of diabetes. Application of erastin, a ferroptosis inducer, reversed the cardioprotective effects of NAC. It is concluded that increased oxidative stress and ferroptosis are the major factors attributable to the increased vulnerability to myocardial IRI in diabetes and that attenuation of ferroptosis represents a major mechanism whereby NAC confers cardioprotection against myocardial IRI in diabetes.

The relation between autophagy modulation by intermittent fasting and aquaporin 2 expression in experimentally induced diabetic nephropathy in albino rat

Polyuria is an early sign of diabetic nephropathy (DN) that produces dehydration in diabetic patients. This could be caused by alteration of renal aquaporin 2 (AQP2) expression. This study aimed to describe the relation between autophagy modulation via intermittent fasting (IF) and renal AQP2 expression and polyuria in case of DN. We divided the rats into control, DN and IF groups. After 2 and 4 weeks of diabetes induction, blood glucose (BG), serum creatinine (Scr), urine volume, and 24 hours urine protein (UP) were examined. Diabetic nephropathy histopathological index (DNHI) was calculated to evaluate histopathological changes. Immunohistochemistry and real-time PCR were performed to measure the levels of AQP2 and the autophagy marker; LC3 in kidney tissue. DNHI was correlated to the PCR and immunoexpression of AQP2 and LC3. Intermittent fasting significantly decreased the BG, Scr, urine volume, 24 hours UP, and DNHI as compared diabetes. Diabetes significantly elevated the immunoreactivity and mRNA expression levels of AQP2 and LC3 as compared to the control. However, the IF decreased AQP2 and stimulated autophagy in cyclic fashion. Our data revealed significant positive correlations between AQP2 and LC3 at the level of immunoexpression and mRNA at 2nd weeks. Taken together, these data showed that autophagy stimulation didn’t regulate AQP2 expression in case of diabetic nephropathy, however IF decreased polyuria through improvement of glycemic state.

Investigation of the synergistic effect of asenapine maleate with fluoxetine on ketamine induced behavioural effects and estimation of brain monoamine in rats

Asenapine maleate (ASM), a potent antipsychotic for schizophrenia, has low oral bioavailability due to Cytochrome P450-1A2 metabolism and has been linked to depression side effects. Aim of the study is to investigate the effect of Asenapine Maleate-Fluoxetine combination. By decreasing CYP1A2, FLX could boost the bioavailability and effectiveness of ASM while reducing its side effects. The increased immobility time in ASM with FLX treated group compared to disease control while rearing and ambulation activities were significantly higher in the ASM, FLX, and combination compared to the disease control group, grooming was significantly lower in the ASM-treated and in the combination compared to the disease group. The Dopamine is significantly decreased in FLX and ASM with FLX treated group, the 5-Hydroxytryptamine is higher in all other groups except disease control and the noradrenaline concentration was higher in the ASM and ASM with FLX compared to the disease control group. The ASM and FLX show synergistic action, after dose, there is substantial cataleptic activity due to dopamine receptor blockade in the nigrostriatal pathway, causing muscular stiffness. Further research is required to prevent catalepsy and excessive diabetes induction due to the combination of ASM and FLX.

Co-administration of “L-Lysine, Vitamin C, and Zinc” increased the antioxidant activity, decreased insulin resistance, and improved lipid profile in streptozotocin-induced diabetic rats

PurposeWe previously showed the beneficial effect of L-Lysine (Lys), a chemical chaperone, on reducing diabetic complications in diabetic rats and type 2 diabetic patients. Herein, we evaluated the effect of Lys co-administration with Vitamin C and Zinc (Lys+VC+Zn), in diabetic rats. MethodsThe streptozotocin (50 mg/Kg) was injected into male adult Wistar rats to induce diabetes. Then, different groups of normal and diabetic rats were treated with Lys and Lys+VC+Zn for five months. So, there were 0.1 % Lys in the drinking water of both groups. The control groups received water alone. During the experiment, the body weight, and various parameters were determined in the blood, serum/plasma, and urine of the rats. ResultsThe determination of biochemical indexes confirmed diabetes induction and its complications in rats. Treatment with either Lys or Lys+VC+Zn resulted in reduced blood glucose and protein glycation (decreasing AGEs and HbA1c), increased insulin secretion, alleviated insulin resistance and HOMA-IR, improved lipid profile and HDL functionality (LCAT and PON1), enhanced antioxidant status (FRAP and AOPP), improved kidney function (decreased microalbuminuria, serum urea, and creatinine), and increased chaperone capacity (HSP70). Lys+VC+Zn showed better effects on these parameters than Lys alone. ConclusionsThe results of this study indicated that co-administration of Lys, a chemical chaperone, with two antioxidants (VC and Zn) potentiates its antidiabetic effects and prevent diabetic complications in rat model of diabetes.

Boosting wound healing in diabetic rats: The role of nicotinamide riboside and resveratrol in UPR modulation and pyroptosis inhibition

BackgroundDiabetes-related skin ulcers provide a substantial therapeutic issue, sometimes leading to amputation, needing immediate practical treatments for efficient wound care. While the exact mechanisms are unknown, pyroptosis and deregulation of the unfolded protein response (UPR) are known to exacerbate inflammation. Nicotinamide Riboside (NR) and Resveratrol (RV), which are known for their Nicotinamide adenine dinucleotide (NAD+) boosting and anti-inflammatory properties, are being studied as potential treatments. The purpose of this study was to shed light on the underlying molecular mechanisms and explore the medical application of NR and RV in diabetic wound healing. Methods54 male Sprague-Dawley rats divided into control, diabetic (DM), Gel Base, DM-NR, DM-RV, and DM-NR + RV. Rats were orally administered 50 mg/kg/day of RV and 300 mg/kg/day of NR for 5 weeks. Following diabetes induction, their wounds were topically treated with 5 % NR and RV gel for 15 days. The wound closure rate, body weight, and serum lipid profiles were examined. Gene expression study evaluated UPR and pyroptosis-related genes (BIP, PERK, ATF6, IRE1α, sXBP1, CHOP, NLRP3, caspase-1, NFκB, and IL1-β) in wound tissues, alongside histological assessment of cellular changes. ResultsNR and RV treatments greatly enhanced wound healing. Molecular investigation demonstrated UPR and pyroptosis marker modifications, suggesting UPR balance and anti-inflammatory effects. Histological investigation demonstrated decreased inflammation and increased re-epithelialization. The combination of NR and RV therapy had better results than either treatment alone. ConclusionThis study shows that NR and RV have therapeutic promise in treating diabetic wounds by addressing UPR dysregulation, and pyroptosis. The combination therapy is a viable strategy to improving the healing process, providing a multimodal intervention for diabetic skin ulcers. These findings pave the way for additional investigation and possible therapeutic applications, giving hope for better outcomes in diabetic wound care.

Flavonoid-Rich Trianthema decandra Ameliorates Cognitive Dysfunction in the Hyperglycemic Rats.

The present study was aimed at the evaluation of neuroprotective ability of methanolic extract of Trianthema decandra (METD) against hyperglycemia-related cognitive impairment in rats. The extract of T. decandra was standardized by TLC and HPTLC methods. To verify the identity and purity of isolated compounds, they were segregated and characterized using various techniques, including UV-visible spectrophotometry, FT-IR, H-NMR, and Mass spectroscopy. α-Amylase and α-glucosidase inhibition property of the extracts were assessed in-vitro. The screening of the neuroprotective effects of METD in hyperglycemic rats was done utilizing Morri's water (MWM) and elevated plus maze (EPM) model, as well as acetylcholinesterase (AChE) activity. The extracts of Trianthema decandra and its chemical constituents, namely quercetin and phytol, demonstrated a significant protective effect on enzymes like α-amylase and α-glucosidase. Methanol and hydroalcoholic extracts have shown the strongest inhibitory activity followed by chloroform extract. Quercetin and phytol were associated with the methanolic and chloroform extracts which were identified using TLC and HPTLC techniques. During the thirty days of the study, the induction of diabetes in the rats exhibited persistent hyperglycemia, hyperlipidemia, higher escape latency during training trials and reduced time spent in target quadrant in probe trial in Morris water maze test, and increased escape latency in EPM task. Regimen of METD (200 and 400 mg/kg) in the diabetic rats reduced the glucose levels in blood, lipid, and liver profile and showed positive results on Morri's water and elevated plus maze tasks. During the investigation, it was determined that Trianthema decandra extracts and the chemical constituent's quercetin and phytol in it had anti-diabetic and neuroprotective activities.

Evaluation of the Neuroprotective Action of &lt;i&gt;Azadirachta indica&lt;/i&gt; Leaves Extract in Streptozotocin-induced Diabetic Rodent Model

Among the most common and painful consequences of diabetes mellitus, Diabetic Peripheral Neuropathy (DPN) is one of the most common. For DPN management, a variety of techniques have been used, ranging from traditional medicines to alternative approaches. Natural compounds are also the focus of research to explore the possible treatment by replacing or combining with the existing therapies. Different neurological changes in diabetic neuropathy and the effect of the Azadirachta indica (neem) extract were assessed with nerve conduction velocity, and biochemical and histological analysis in Streptozotocin-induced diabetic mellitus. The therapeutic effect of the extract was evaluated with doses 100, 200 and 500mg/kg body weight for 4 weeks after induction of diabetes. The protective effect was evaluated by treating the animals with hydroalcoholic extract of neem leaves in 500mg/kg dose before the induction of diabetes and post-treatment with the standard drug Metformin (500mg/kg). Both resulted in a significant reduction in blood glucose, additionally, 500mg/kg body weight dose revealed the signs of neuroprotection in diabetic rats. Neem leaf extract appears to be promising for future investigations, which might contribute to the emergence of new drugs for diabetes treatment and diabetic neuropathy either alone or in combination with conventional therapies.

The Protective Effects of Vanillic Acid and Vanillic Acid-Coated Silver Nanoparticles (AgNPs) in Streptozotocin-Induced Diabetic Rats.

The production of nanoparticles enhances the bioactivity of biological molecules for drug delivery to diseased sites. This study explains how silver nanoparticle (AgNP) coating enhanced the protection effects of vanillic acid in male diabetic rats with streptozotocin- (STZ-) induced diabetes. Twenty-four rats were divided into four groups (n = 6) for this investigation. The first group (G1) is untreated, whereas diabetes was induced in the other three groups through STZ injection. Diabetic rats that were not getting therapy were included in the second group (G2, STZ-positive), whereas the other diabetic rats were divided into the third group (G3, vanillic acid-treated) and the fourth group (G4, vanillic acid-coated AgNPs treated). The treatment lasted four weeks. In G2, the induction of diabetes significantly (at P = 0.05) increased in serum glucose, glycated proteins, renal indices, interleukin-6 (IL-6), K+, immunoglobulins, and lipid peroxidation, while decreased Ca++, Na+, and other antioxidants in the kidney tissue homogenate. In addition, pathological altered signs were present in the pancreas and kidneys of diabetic rats. The renal and pancreatic tissues were effectively enhanced by vanillic acid or vanillic acid-coated AgNPs, bringing them very close to their prediabetic conditions. Vanillic acid-coated AgNPs offered a stronger defense against STZ-induced diabetes and lessened the effects of hyperglycemia compared to ordinary vanillic acid. Additionally, using vanillic acid coated with silver nanoparticles greatly increased the antioxidant and antidiabetic activity and reduced inflammation when compared to using vanillic acid alone.

Liver and Kidney Biochemical Markers in Alloxan Induced Diabetic Wistar Rats: Effects of Buchholzia coriacea Seed Alcoholic Extract

The chronic hyperglycemia of diabetes is associated with long-term damage, dysfunction, and failure of various organs. Therefore, the objective of this paper was to assess the effects of wonderful kola (Buchholzia coriacea) on biochemical markers such as liver and kidney in alloxan induced diabetic Wistar rats using appropriate standard techniques. The result showed that Buchholzia coriacea seed extract caused significant (p&lt;0.05) reduction in the levels of glucose. The liver function test revealed notable changes in the negative control group compared to the control group, including elevated levels of AST, ALT, ALP, and T.P (*p&lt;0.05). Treatment with Metformin and the high dose of Wonderful Kola exhibited significant improvements in AST, ALT, and ALP levels compared to the negative control (#p&lt;0.05), suggesting potential hepatoprotective effects. The kidney function test, revealed notable difference In comparison to the control group, the negative control group showed significantly (p&lt;0.05) elevated levels of Urea, Creatinine, K, Na, Cl, T.B, and C.B. Treatment with Metformin demonstrated a significant (p&lt;0.05) decrease in Urea and Creatinine levels compared to the negative control. The low and high doses of Wonderful Kola resulted in significant (p&lt;0.05) reductions in Urea, Creatinine, and T.B levels, with the high dose also significantly decreasing Na and Cl levels compared to the negative control. The methanoic extract of Buchholzia coriacea seed possess hypoglycemic properties and may therefore be beneficial in the management of diabetes mellitus at the above dosage and treatment period. Buchholzia coriacea especially at high doses exhibited protective effects on the liver and kidney biochemical markers in alloxan induced diabetic rats, highlighting its potential as a therapeutic agent.

Hepatic and renal effects of oral stingless bee honey in a streptozotocin-induced diabetic rat model.

Diabetes is known damage the liver and kidney, leading to hepatic dysfunction and kidney failure. Honey is believed to help in lowering the blood glucose levels of diabetic patients and reducing diabetic complications. However, the effect of stingless bee honey (SBH) administration in relieving liver and kidney damage in diabetes has not been well-studied. To investigate the effect of SBH administration on the kidney and liver of streptozotocin-induced (STZ; 55 mg/kg) diabetic Sprague Dawley rats. The rats were grouped as follows (n = 6 per group): non-diabetic (ND), untreated diabetic (UNT), metformin-treated (MET), and SBH+metformin-treated (SBME) groups. After successful diabetic induction, ND and UNT rats were given normal saline, whereas the treatment groups received SBH (2.0 g/kg and/or metformin (250 mg/kg) for 12 d. Serum biochemical parameters and histological changes using hematoxylin and eosin (H&E) and periodic acid-Schiff (PAS) staining were evaluated. On H&E and PAS staining, the ND group showed normal architecture and cellularity of Bowman's capsule and tubules, whereas the UNT and MET groups had an increased glomerular cellularity and thickened basement membrane. The SBH-treated group showed a decrease in hydropic changes and mild cellularity of the glomerulus vs the ND group based on H&E staining, but the two were similar on PAS staining. Likewise, the SBME-treated group had an increase in cellularity of the glomerulus on H&E staining, but it was comparable to the SBH and ND groups on PAS staining. UNT diabetic rats had tubular hydropic tubules, which were smaller than other groups. Reduced fatty vacuole formation and dilated blood sinusoids in liver tissue were seen in the SBH group. Conversely, the UNT group had high glucose levels, which subsequently increased MDA levels, ultimately leading to liver damage. SBH treatment reduced this damage, as evidenced by having the lowest fasting glucose, serum alanine transaminase, aspartate transaminase, and alkaline phosphatase levels compared to other groups, although the levels of liver enzymes were not statistically significant. The cellularity of the Bowman's capsule, as well as histological alteration of kidney tubules, glomerular membranes, and liver tissues in diabetic rats after oral SBH resembled those of ND rats. Therefore, SBH exhibited a protective hepatorenal effect in a diabetic rat model.

A Recombinant Peptide Device Combined with Adipose Tissue-Derived Stem Cells Enhances Subcutaneous Islet Engraftment.

Subcutaneous space has been considered an attractive site for islet graft transplantation; however, the oxygen tension and vascularization are insufficient for islet graft survival. We investigated whether subcutaneous pre-implantation of a recombinant peptide (RCP) device with adipose tissue-derived stem cells (ADSCs) enhanced subcutaneous islet engraftment. RCP devices with/without syngeneic ADSCs were pre-implanted into the subcutaneous space of C57BL/6 mice. Syngeneic islets (300 or 120 islet equivalents (IEQs)) were transplanted into the pre-treated space after diabetes induction using streptozotocin. The cure rates of groups in which RCP devices were implanted four weeks before transplantation were significantly better than the intraportal transplantation group when 300 IEQs of islets were transplanted (p < 0.01). The blood glucose changes in the RCP+ADSCs-4w group was significantly ameliorated in comparison to the RCP-4w group when 120 IEQs of islets were transplanted (p < 0.01). Immunohistochemical analyses showed the collagen III expression in the islet capsule of the RCP+ADSCs-4w group was significantly enhanced in comparison to the RCP-4w and RCP+ADSCs-d10 groups (p < 0.01, p < 0.01). In addition, the number of von Willebrand factor-positive vessels within islets in the RCP+ADSCs-4w group was significantly higher than the RCP-4w group. These results suggest that using ADSCs in combination with an RCP device could enhance the restoration of the extracellular matrices, induce more efficient prevascularization within islets, and improve the graft function.

Evaluation of serum pro/anti-angiogenic biomarkers in hyperglycemic rats treated with Securigera securidaca seeds, alone and in combination with Glibenclamide.

Herbal medicines are commonly used by many people with diabetes in addition to standard treatment. Plants contain numerous known and unknown compounds that may exacerbate or ameliorate diabetes complications. Therefore, it is crucial to be aware of the side effects of these herbs before prescribing them. This study aimed to investigate the effects of hydroalcoholic extracts of Securigera securidaca (HESS) seeds alone and in combination with glibenclamide on the angiogenic/anti-angiogenic balance in streptozotocin (STZ)-induced diabetic rats. Groups involved in this animal study included diabetic and healthy controls, three doses of HESS, glibenclamide, and combination therapy. Serum samples were collected and analyzed for a vascular endothelial growth factor (VEGF), fibroblast growth factor 21 (FGF21), fetal liver kinase 1 (FLK-1), soluble fms-like tyrosine kinase 1 (sFLT-1), and transforming growth factor -beta (TGF-β). Induction of diabetes increased VEGF, FGF21, and TGF-β serum levels and decreased circulating FLK-1 and sFLT-1 factors. Herbal extract, except TGF-β, had little effect on the above blood levels even at the highest doses. Glibenclamide was more effective than the highest dose of HESS in improving the vascular complications of diabetes. Combination therapy with the highest dose of HESS partly enhanced the glibenclamide effects. Compared with glibenclamide as a standard chemical drug, HESS had no significant effects on the blood levels of the pro/anti-angiogenesis factor in diabetic rats. Glibenclamide attenuated the levels of the biomarkers and its effects were somewhat enhanced in combination with the highest dose of HESS.

Bone Marrow-Derived C-Kit+ Cells Improved Inflammatory IL-33/ST-2/ILC2 Axis in the Lung Tissue of Type 2 Diabetic Rats.

Inflammation is an essential factor in pulmonary complications of diabetes. Bone marrow (BM)-derived C-kit+ cells have immunomodulatory properties and their transplantation is suggested as a promising strategy for ameliorating diabetes complications. This study evaluated the effect of BM-derived C-kit+ cells on the inflammation signaling pathway in lung tissue of type 2 diabetic male rats. Ten rats were used to extract C-kit cells, and 48 male Wistar rats weighing 180 ± 20 g were randomly divided into four equal groups: (1) Control (Cont), (2) Diabetic (D), (3) Diabetic + C-kit+ cells (D + C-kit pos) intravenously injected 50-µl phosphate buffer saline (PBS) containing 300,000C-kit+ cells, and (4) Diabetic + C-kit- cells (D + C-kit neg), intravenously injected C-kit- cells. Diabetes induction increased IL-33, ST-2, CD127, and IL-2 levels and decreased IL-10. C-kit+ cell therapy significantly decreased IL-33 and CD127 and increased IL-10. In addition, lung histopathological changes significantly improved in the C-kit+ group compared to the diabetic group. These findings suggest that C-kit+ cells may have a potential therapeutic role in mitigating diabetes-induced respiratory complications via ameliorating the inflammation and histopathological changes in lung tissue.