Experimentally-induced Diabetes Research Articles

The levels of adropin and its therapeutic potential in diabetes.

Adropin, a peptide hormone encoded by the ENHO gene is expressed in various tissues including the brain. Accumulating evidence from in vivo and in vitro studies highlights adropin's pivotal role in modulating carbohydrate and lipid metabolism. Notably, circulating adropin levels are lower in overweight and obese humans and experimental interventions involving adropin overexpression or synthetic administration demonstrate promising outcomes in mitigating obesity-related metabolic abnormalities and preventing weight gain. This review comprehensively summarizes current understanding of adropin's potential implications in diverse types of diabetes. Specifically, it explores adropin's utility as a biomarker for different types of diabetes and elucidates its significance as a potential predictor of diabetic adverse outcomes. Furthermore, the review delves into the beneficial effects of adropin treatment in animal models of experimentally-induced diabetes, shedding light on its mechanisms of action in modulating glucose metabolism. In this comprehensive overview, we aim to provide a nuanced understanding of multifaceted role of adropin in diabetes pathogenesis and its therapeutic potential in combating this global health challenge.

Knockdown of SIRT3 perturbs protective effects of irisin against bone loss in diabetes and periodontitis.

A well-recognized risk factor for periodontitis, diabetes mellitus (DM) aggravates periodontal disease with increasing alveolar bone loss. As a novel myokine, irisin is closely linked with bone metabolism. Nonetheless, the effects of irisin on periodontitis under diabetic conditions and the underlying mechanisms remain poorly understood. Here, we showed that local irisin treatment ameliorates alveolar bone loss and oxidative stress, increases SIRT3 expression within periodontal tissues of our experimentally-induced diabetes and periodontitis (DP) rat models. By culturing the periodontal ligament cells (PDLCs) in vitro, we found that irisin could partially rescue inhibited cell viability, mitigate accumulated intracellular oxidative stress, ameliorate mitochondrial dysfunctions, and restore disturbed osteogenic and osteoclastogenic capacities of PDLCs when exposed to high glucose and pro-inflammatory stimulation. Furthermore, lentivirus-mediated SIRT3 knockdown was employed to unravel the underlying mechanism by which SIRT3 mediated irisin's beneficial effects on PDLCs. Meanwhile, in SIRT3-deficient mice, irisin treatment did not protect against alveolar bone destruction and oxidative stress accumulation in DP models, which underlined the crucial role of SIRT3 in mediating the positive effects of irisin on DP. Our findings, for the first time, revealed that irisin attenuates alveolar bone loss and oxidative stress via activation of the SIRT3 signaling cascade, and highlighted its therapeutic potential for the treatment of DP.

The effect of experimentally-induced diabetes on rat hippocampus and the potential neuroprotective effect of Cerebrolysin combined with insulin. A histological and immunohistochemical study

ABSTRACT Diabetes Mellitus is the most common metabolic disorder affecting central nervous system (CNS) and is associated with altered brain structure. In this study, we assessed the ability of Cerebrolysin, alone and combined with insulin, to protect from the hippocampal degenerative changes in a diabetic rat model. Sixty adult male albino rats were equally divided into: control (gpI), diabetic (gpII), insulin-treated (gpIII), Cerebrolysin-treated (gpIV) and combined Insulin & Cerebrolysin-treated groups (gpV). Type-1 DM was induced by a single intraperitoneal injection of Streptozotocin (65 mg/kg) in groups (II, III, IV & V). Insulin was given subcutaneously (1 U/100g) daily, starting from the 4th day till the end of the experiment. Cerebrolysin was given intraperitonealy (5 ml/kg/day), starting from the 4th day till the end of the experiment. Hippocampus samples were collected 8-weeks post-injection. Hematoxylin & Eosin (H&E) and Immunohistochemical stains were used to assess the degenerative changes. The rat hippocampal region (CA3) and the dentate gyrus (DG) were subjected to microscopic examination and morphometric analysis. The hippocampus of rats of group II showed evident degenerative changes. Changes in immunohistochemical expression of Bax, TNF-alpha, Synaptophysin & GFAP were also detected. The morphometric study revealed changes in the thickness of layers and number of cells. Groups III and IV showed mild improvement in most parameters. Group V demonstrated marked improvement in most parameters and the hippocampus appeared more or less similar to the control. Cerebrolysin is a neurotropic drug that protects from the diabetic degenerative changes, especially if combined with insulin.

Investigation of the Effects of N-Acetylcysteine on Asprosin Hormone Activity and Liver Tissues in Rats with Experimentally-Induced Diabetes

Objective: To investigate the possible effect of N-acetylcysteine (NAC) treatment on rat diabetes-induced liver damage and immune reactivity of asprosin hormone in the liver. Material-Method: Twenty-eight Wistar albino male rats were used in the study. They were separated into 4 groups as Control (n=7), Diabetes (n=7), Diabetes+NAC (n=7), and NAC (n=7). The rats in all groups were dissected after the treatment, and liver tissues were taken for pathological examination. Tissue sections were stained with immunohistochemistry for detecting asprosin immunoreactivity, hematoxylin-eosin and picrosirius red staining were performed to determine the changes in the tissues. Result: In the microscopical examination of hematoxylin-eosin-stained sections normal histological hepatic tissues were seen in the Control and NAC groups. Pathological examination of liver tissue from diabetic rats showed marked dissociation, fibrosis, degeneration, inflammation, necrosis, Kupffer cells activation, bile duct proliferation, and congestion. A significant decrease in these lesions was observed in the DM+NAC group. Immunohistochemical studies showed that asprosin immunoreactivity was increased in the DM group in a significant manner. Asprosin expression was observed to be significantly reduced in the DM+NAC group in comparison to the DM group. Conclusion: Our findings show that NAC administration reduces liver damage in diabetic rats and can be used to reduce/eliminate the negative effects of diabetes in rat liver tissue.

A Systematic Review of the Potential Effects of Propolis Extracts on Experimentally-induced Diabetes.

Oxidative stress (OS) is involved in the development of diabetes mellitus (DM) and its complications. Thus, OS reduction may be an important strategy for DM therapy. Propolis is bee resins with high antioxidant activity and is used in the treatment of different diseases, including DM. Therefore, in this systematic review, we evaluated the impact of propolis administration in diabetic animals. We used the PRISMA strategy to collect preclinical studies published in English up to November 2021 in three databases (PubMed/Medline, Scopus, and Web of Science). We used the SYRCLE tool to analyze the risk of methodological bias. Our primary search returned 198 studies, of which 14 were considered eligible to be included in this review. The administration of propolis induced a hypoglycemic effect in the treated animals, which is probably due to the reduction of OS. The animals showed restoration of endogenous antioxidant defenses and reduced levels of markers for OS. The administration of propolis resulted in improvement in the lipid profile of treated animals. Our risk of bias assessment showed a methodological quality score of less than 30% due to a lack of randomization, blinding, and proper allocation of animals. Heterogeneity in treatments, lack of results, and use of non-standard extracts are limitations in our data analysis. Despite these limitations, propolis induced a significant hypoglycemic effect in diabetic animals when compared to untreated controls. This effect was associated with a reduction in OS, a process mediated by ROS neutralization and restoration of endogenous antioxidant defenses.

Ascorbic acid alleviates oxidative stress and improves major salivary glands’ structure and function in diabetic rats: A histological and immunohistochemical study

Diabetes Mellitus and the associated hyperglycemia trigger oxidative damage to tissues and organs. DM is obviously related to the salivary glands’ dysfunction. Ascorbic acid is a powerful dietary antioxidant. In this study, we investigated the ascorbic acid’s putative potential to conserve the structure and function of the major salivary glands in diabetic patients. Adult male albino rats (n = 24) were equally divided into four groups: Group I (control, only distilled water), Group II (ascorbic acid 200 mg/Kg/day), Group III (experimentally-induced diabetes by single intraperitoneal injection of streptozotocin 60 mg/kg), and Group IV (ascorbic acid after one week of diabetes induction). Blood glucose level was assessed. After eight weeks, samples from the salivary glands were processed for histopathological and immunohistochemical examination. Group III showed degenerative changes in the salivary glands and increased collagen deposition, whereas the glycoprotein content and antiapoptotic activity decreased. Group IV showed marked histologic and functional improvement. Although further research is required to fully understand its mode of action, ascorbic acid is advised as an adjuvant medication for diabetes to keep the integrity of major salivary glands.

Investigation of Pomegranate Seed Oil Effects on the Renal Function in Alloxan-induced Diabetic Male Rabbits

Diabetes is a chronic disease which has reached pandemic proportions in a lot of countries of the world. In spite of the remarkable development in therapeutics chemistry, the usage of customary drugs is still a common practice for the treatment of diabetes. The current study was designed to investigate the effects of pomegranate seed oil (PSO) on kidney functions in the experimentally-induced diabetes in male rabbits. Diabetes was experimentally introduced by the intraperitoneal injection of alloxan monohydrate (150mg/kg BW). After three days of alloxan injection, samples were taken for the determination of glucose concentration. Serum glucose concentration of 200mg/ml was considered as an indication of animal diabetes. The experimental part was begun after 7 days of alloxan injection.
 Thirty two adult male rabbits were arbitrarily separated into four groups and treated daily for 45 days. Group 1 was kept with no treatment, group 2 included animals treated with 30mg/kg BW PSO, group 3 included diabetic animals that received alloxan with a dose of 150mg/kg BW, and, finally, group 4 included animals that received alloxan (150mg/kg BW) and treated with PSO (30mg/kg BW). Fasting blood samples were collected by heart puncture technique after 45days of experiments to assess glucose levels.

Amelioration of Diabetes-Induced Nephropathy by Loranthus regularis: Implication of Oxidative Stress, Inflammation and Hyperlipidaemia

In traditional Yemeni medicine, various preparations of Loranthus regularis (L. regularis), such as powder, decoctions and infusions are commonly used to treat diabetes, kidney stone formations and inflammation. In the present study, we evaluated the antinephrotoxic effects of L. regularis extract in experimentally-induced diabetes in male Wistar rats. A single dose (60 mg/kg/day) of Streptozotocin (STZ) was used to induce type 1 diabetes. Animals were then treated for four weeks with L. regularis extract (150 or 300 mg/kg/day) by oral gavage. Renal and blood samples were subsequently harvested. Several biochemical indices, oxidative stress and inflammatory markers were assessed. Additionally, histological alterations in the renal tissue were examined. Serum glucose levels were significantly (p < 0.01) lowered while insulin levels were enhanced in L. regularis-treated diabetic animals. The increased renal markers in diabetic rats were decreased by L. regularis treatment. Serum elevated lipid profiles were markedly decreased by the plant extract. The serum and renal cytokines that were significantly increased (p < 0.001) by STZ were diminished by L. regularis treatment. Finally, renal tissue antioxidant enzymatic activity was enhanced with L. regularis treatment. Taken together, the data here indicate that L. regularis possesses therapeutic ability to reduce the development of diabetic nephropathy (DN) by minimizing oxidative injury and inflammation.

Adenosine A2A and A3 Receptors as Targets for the Treatment of Hypertensive-Diabetic Nephropathy.

Diabetic nephropathy (DN) and hypertension are prime causes for end-stage renal disease (ESRD) that often coexist in patients, but are seldom studied in combination. Kidney adenosine levels are markedly increased in diabetes, and the expression and function of renal adenosine receptors are altered in experimental diabetes. The aim of this work is to explore the impact of endogenous and exogenous adenosine on the expression/distribution profile of its receptors along the nephron of hypertensive rats with experimentally-induced diabetes. Using spontaneously hypertensive (SHR) rats rendered diabetic with streptozotocin (STZ), we show that treatment of SHR-STZ rats with an agonist of adenosine receptors increases A2A immunoreactivity in superficial glomeruli (SG), proximal tubule (PCT), and distal tubule (DCT). Differently, treatment of SHR-STZ rats with a xanthinic antagonist of adenosine receptors decreases adenosine A3 immunoreactivity in SG, PCT, DCT, and collecting duct. There is no difference in the immunoreactivity against the adenosine A1 and A2B receptors between the experimental groups. The agonist of adenosine receptors ameliorates renal fibrosis, probably via A2A receptors, while the antagonist exacerbates it, most likely due to tonic activation of A3 receptors. The reduction in adenosine A3 immunoreactivity might be due to receptor downregulation in response to prolonged activation. Altogether, these results suggest an opposite regulation exerted by endogenous and exogenous adenosine upon the expression of its A2A and A3 receptors along the nephron of hypertensive diabetic rats, which has a functional impact and should be taken into account when considering novel therapeutic targets for hypertensive-diabetic nephropathy.

Reversal of Diabetic Complications in Andrology Parameters of Alloxan-Induced Diabetic Male Wistar Rats Treated with Cleome rutidosperma Leaves

Abstract Male infertility is one of the complications associated with diabetes mellitus. This study reported the effect of managing experimentally-induced diabetes in male Wistar rats with Cleome rutidosperma leaf extract at doses of 100 mg.kg−1, 200 mg.kg−1 or 400 mg.kg−1 for 14 days. Further deterioration or amelioration of reproductive derangement was assessed by changes in sperm morphology, sperm characteristics, and testicular histo-pathology. Andrology profile of diabetic untreated rats showed significant (P < 0.05) derangements compared to normoglycaemic rats. The profile of diabetic rats treated with the extract of C. rutidosperma, especially at the 200 mg.kg−1 dose showed a significant decrease in abnormal sperm cells, increases in sperm motility, live/ dead ratio and count compared to the untreated diabetic rats. Histopathology showed spermatogenic arrest and degeneration of Sertoli cells in the diabetic untreated rats, but was restored in the C. rutidosperma treated rats. This study showed evidence of infertility associated with diabetes and the ameliorative ability of C. rutidosperma on infertility demonstrated by improved andrological parameters. Traditional management of diabetes with C. rutidosperma leaves should therefore be encouraged in both humans and other animals, especially males with reproductive intentions.

Protective effect of alpha lipoic acid on diabetic nephropathy in rats

Objective: To evaluate the protective role of alpha lipoic acid in rats affected with experimentally-induced diabetes and secondarily complicated with nephropathy. Design: Randomized controlled study. Animals: Forty-eight Sprague Dawley rats. Procedures: Rats were allocated randomly into four groups (12 each); Control rats (Group 1); alpha lipoic acid (ALA) supplemented rats (Group 2); rats with induced diabetic nephropathy (Group 3), and rats with diabetic nephropathy and supplemented with alpha lipoic acid (Group 4). After one month of experimental induction, serum, plasma and renal tissue samples were harvested to determine glycemic status, renal damage markers, antioxidant status, oxidative and nitrosative stress markers, apoptotic marker and histopathology of kidney tissues. Results: In comparison with non-supplemented diabetic rats, alpha lipoic acid reduced renal malondialdehyde (5.74± 0.26 vs 11.3± 1.96 nmol/g. tissue) and renal nitric oxide (30.06± 2.07 vs 36.6± 1.07 nmol/g. tissue). ALA significantly improved the antioxidant enzyme activity (catalase and reduced glutathione), glycemic status, and decreased caspase 3 concentration (P<0.05). Conclusion and clinical relevance: Alpha lipoic acid may be an alternative intervention to alleviate nephropathy as a complication of diabetes. Further studies need to be done in naturally occurring cases.

Protective effect of alpha lipoic acid on diabetic nephropathy in rats

Objective: To evaluate the protective role of alpha lipoic acid in rats affected with experimentally-induced diabetes and secondarily complicated with nephropathy. Design: Randomized controlled study. Animals: Forty-eight Sprague Dawley rats. Procedures: Rats were allocated randomly into four groups (12 each); Control rats (Group 1); alpha lipoic acid (ALA) supplemented rats (Group 2); rats with induced diabetic nephropathy (Group 3), and rats with diabetic nephropathy and supplemented with alpha lipoic acid (Group 4). After one month of experimental induction, serum, plasma and renal tissue samples were harvested to determine glycemic status, renal damage markers, antioxidant status, oxidative and nitrosative stress markers, apoptotic marker and histopathology of kidney tissues. Results: In comparison with non-supplemented diabetic rats, alpha lipoic acid reduced renal malondialdehyde (5.74± 0.26 vs 11.3± 1.96 nmol/g. tissue) and renal nitric oxide (30.06± 2.07 vs 36.6± 1.07 nmol/g. tissue). ALA significantly improved the antioxidant enzyme activity (catalase and reduced glutathione), glycemic status, and decreased caspase 3 concentration (P&lt;0.05). Conclusion and clinical relevance: Alpha lipoic acid may be an alternative intervention to alleviate nephropathy as a complication of diabetes. Further studies need to be done in naturally occurring cases.

Effect of hesperidin treatment on α-Klotho/FGF-23 pathway in rats with experimentally-induced diabetes

Objective Non-alcoholic fatty liver disease, steatohepatitis and nephropathy are considered among the most important complications of diabetes mellitus (DM), which recently increased due to increased frequency of DM and the prolonged life span of diabetic patients The aim of the present study was to reveal the possible effect of hesperidin (HP) on alpha-klotho (α-KL)/ fibroblast growth factor-23 (FGF-23) pathway in rats with diabetes induced by streptozotocin (STZ).Materials and methods Thirty six male Sprague-Dawley rats were randomly divided into three groups. The rats of the control, diabetes, and treatment groups were fed with standard feed and water throughout the 2-week study. In order to induce diabetes mellitus in rats, those in the diabetes group were administered a single dose of 50 mg/kg STZ. For the DM + HP group, a single dose of 50 mg/kg STZ, when diabetes was induced, hesperidin was administered orally at a dose of 100 mg/kg by gavage.Results The α-KL levels of our study groups, both the liver and kidney α-KL levels and serum α-KL of the STZ-induced diabetic group were statistically significantly lower than the control group (respectively, p < 0.05, p < 0.001, p < 0.05). It was observed that hesperidin administration statistically significantly increased α-KL levels in serum, liver and renal tissue (p < 0.001). Liver, kidney and serum FGF-23 levels of the diabetic group increased significantly in comparison to the control group (respectively, p < 0.05, p < 0.01, p < 0.001). FGF-23 levels that increased in kidney tissue and serum samples of the diabetic group decreased statistically significantly with hesperidin administration (respectively, p < 0.01, p < 0.001).Conclusion The α-KL/FGF-23 pathway is a promising bio-indicator in various cases of systemic toxicity and pathology. In addition, the strong positive effects of hesperidin administration on diabetic toxicity in the liver and kidneys suggest that it may be included in the alternative treatment methods in the future.

High-fat diet and type 2 diabetes induced disruption of the oestrous cycle and alteration of hormonal profiles, but did not affect subpopulations of KNDy neurones in female rats.

Apart from the primary metabolic symptoms of obesity and/or diabetes, there are numerous secondary problems, including disruptions of the reproductive system. The KNDy neurones, which express kisspeptin, neurokinin B and dynorphin A and are located in the arcuate nucleus of the hypothalamus (ARC), are important regulators of reproduction. Their functions are highly influenced by metabolic and hormonal status. We have previously shown that, in male rats with experimentally-induced diabetes type 2 (but not with high-fat diet-induced obesity), there are alterations in the number of these cells. In the present study, we hypothesised that a high-fat diet (HFD) and/or diabetes type 2 (DM2) in female rats affect the oestrous cycle, hormonal profiles and the number of kisspeptin-immunoreactive, neurokinin B-immunoreactive and/or dynorphin A-immunoreactive neurones in the ARC. Rats were assigned to one of three groups: a control group fed a regular chow diet, a high-fat diet group (HFD) and a diabetic group (DM2), with both of the latter two groups receiving a high calorie diet (50% of energy from lard). The third group was additionally treated with streptozotocin to induce DM2.Their oestrous cycles was monitored and their metabolic and hormonal status were assessed. We found that HFD and DM2 female rats, despite having significant alterations in their metabolic and hormonal profiles, as well as disruptions of the oestrous cycle, showed no changes in the number of the kisspeptin-immunoreactive, neurokinin B-immunoreactive and/or dynorphin A-immunoreactive neurones in the ARC. However, slight differences in the rostrocaudal distribution of these neurones among groups were reported. In conclusion, the data from the present study, together with our previously published results in males, indicate sex differences in the response of KNDy neurones to DM2 but not to HFD conditions.

Olive Leaves Extract Effects on Sperm Quality Following Experimentally-Induced Diabetes in Rats

Background: The experimental model of streptozotocine (STZ)-induced diabetes explains changes in the male reproductive system as part of the disease. Objective: The aim of the present study was to evaluate the olive leaf extract effects on STZ-induced diabetes and to examine its modulatory effects on sperm quality. Methods: Twenty adult male Sprague–Dawley rats were divided into four equal groups: the first group served as untreated control. Groups 2, 3 and 4 of rats were injected STZ (65 mg/kg). The animals which exhibited blood glucose levels higher than 250 mg/dl by days 4-6, were considered as diabetic rats. Groups 3 and 4 received olive leaf extract (100 and 150 mg/kg, orally) and vehicle to the control and diabetic rats (group 2) for 10 consecutive days. Results: Glycated haemoglobin percentage (%HbA1c) as a diabetic index significantly decreased in the animals ingested by the 150 mg/kg of the extract compared to the diabetic group (P

Pinprick hypo- and hyperalgesia in diabetic rats: Can diet content affect experimental outcome?

Existing literature concerning the effect of experimentally-induced diabetes on pain thresholds in rodent models remains controversial. In this work, we describe a phenotypical switch from streptozotocin-induced pinprick hypoalgesia to hyperalgesia observed in the same laboratory, in the same strain of rats, obtained from the same vendor, and measured by the same technique carried out by the investigators. This switch was observed around January 2015, at the time when there was a change in the diet of rats at the Radley North Carolina Charles River facility. These data support the contention that diet may significantly modify disease progression, including progression of signs of diabetic neuropathy.

Changes in Ongoing Activity and Electrophysiological Characteristics of the Rat Retinal Ganglion Cells in Diabetes Mellitus

Changes in electrophysiological characteristics and ongoing activity parameters of the isolated rat retinal ganglion cells were evaluated 3-4 weeks after streptozotocin injection (80 mg/kg). It has been revealed that electrophysiological characteristics significantly decreased. In particular, density of sodium current decreased by 35% (from -0.84 ± 0.14 nA/pF in control to -0.55 ± 0.08 nA/pF in streptozotocin-induced diabetes mellitus; potassium current decreased by 36% (0.87 ± 0.14 in diabetes versus 1.36 ± 0.16 nA/pF in control, and resting membrane potential decreased by 10% (-53 ± 1 mV in diabetes versus -59 ± 1 mV in control. The mean frequency of ongoing postsynaptic currents was reduced by 72% (2...5 ± 0.3 sec-1 in control and 0.7 ± 0.1 sec-1 in diabetes. The data suggest that pathological changes in the electrophysiological characteristics of the rat retinal ganglion cells appear at the early stage of experimentally-induced diabetes mellitus.

Comparative Histological Study on the Effect of Stem Cells, and Gene Modified Stem Cells in Experimentally-Induced Diabetes Type 1 Cardiomyopathy

Background and Objectives: Sarco(endo) plasmic reticulum Ca2+-ATPase (SERCA2a) is the ATP-driven pump thattranslocates Ca2+ from the cytoplasm to the lumen of the sarcoplasmic reticulum. 25% of children and adolescents withtype 1 diabetes will develop diastolic dysfunction that results in part from a reduction in the activity of SERCA2a. Thepresent study aimed at investigating and comparing the therapeutic effect of Adipose Mesenchymal Stem Cells (AMSCs)with SERCA2a gene modified AMSCs in diabetes type 1 induced cardiomyopathy of adult male albino rat.Materials and Methods: Twenty-nine adult male albino rats were divided into: Donor group of 2 rats used to obtainAMSCs. Group I (Control group): 6 rats not exposed to diabetes induction. Group II (Diabetic group): 7 rats injectedwith streptozotocin (STZ) 50mg/Kg once. Group III ( (AMSCs group): 7 rats injected with AMSCs following inductionof diabetes. Group IV (SERCA2a Modified AMSCs Group): 7 rats injected with SERCA2a modified AMSCs, followinginduction of diabetes. All rats were sacrificed 8 weeks from start of experiment.Results: Morphological changes, indicating inflammation and degeneration, were found in the cardiac muscle of diabeticrats and regressed remarkably by AMSCs and SERCA2a modified AMSCs. The regression of morphological changes wasconfirmed by histological, immunohistochemical, morphometric and serological studies.Conclusion: The therapeutic effect of SERCA2a modified AMSCs in diabetes type 1 cardiomyopathy was moreremarkable than that of AMSCs.

SERUM CHEMERIN LEVEL IN RELATION TO RENAL FUNCTION IN EXPERIMENTALLY INDUCED DIABETIC RATS

Background: Chemerin, a recently discovered adipocytokine, regulates adipocyte development and metabolism as well as inflammatory and immune function. Data onto chemerin levels in diabetes and its associated renal affection is limited and controversial. Objective: This work was designed to evaluate the serum chemerin level in acute and chronic experimentally-induced diabetes and its relation to some metabolic parameters, and renal function tests. Materials and Methods: This study was done on 30 adult healthy male of local strain albino rats. Animals were divided into three equal groups, i.e.healthy group, acute diabetic group and chronic diabetic untreated group. Diabetes was induced experimentally by intra peritoneal injection of streptozotocin (STZ). In each of the three groups, each animal was put inside a cage to collect 24h urine tomeasure albuminuria, then they were sacrificed, and sera were examined for levels of glucose, insulin, chemerin , cholesterol, triglycerides (TG), high density lipoproteins (HDL) , Low density lipoproteins (LDL), urea, creatinine, creatinine clearance, C-reactive protein (CRP), and tumor-necrosing factor alpha (TNF-α). Results: There was a significant increase in serum chemerin levels in the chronic diabetic untreated group when compared to both control and acute diabetic groups. Also, there were significant positive correlations between serum chemerin levels and serum urea, creatinine, urine albumin, serum cholesterol, TG, LDL, CRP and TNF-α levels, as well as negative correlations between serum chemerin levels, and both serum creatinine clearance and HDL levels in the chronic diabetic untreated group. Conclusion: Serum chemerin levels seemed to be related to impaired renal function test (albuminuria, serum creatinine, urea and creatinine clearance) rather than to serum insulin level. Serum chemerin levels elevated, without any concomitantsignificant change in serum insulin in chronic diabetic group, when compared to acute diabetic group. Accordingly, it can be hypothesized that the change of serum chemerin could be considered as a predicting marker of diabetic nephropathy rather than of diabetes.

Effects of ageing and experimental diabetes on insulin-degrading enzymeexpressionin male rat tissues.

Due to an increasing life expectancy in developing countries, cases of type 2 diabetes and Alzheimer's disease (AD) in the elderly are growing exponentially. Despite a causative link between diabetes and AD, general molecular mechanisms underlying pathogenesis of these disorders are still far from being understood. One of the factors leading to cell death and cognitive impairment characteristic of AD is accumulation in the brain of toxic aggregates of amyloid-β peptide (Aβ). In the normally functioning brain Aβ catabolism is regulated by a cohort of proteolytic enzymes including insulin-degrading enzyme (IDE) and their deficit with ageing can result in Aβ accumulation and increased risk of AD. The aim of this study was a comparative analysis of IDE expression in the brain structures involved in AD, as well as in peripheral organs (the liver and kidney) of rats, during natural ageing and after experimentally-induced diabetes. It was found that ageing is accompanied by a significant decrease of IDE mRNA and protein content in the liver (by 32 and 81%) and brain structures (in the cortex by 58 and 47% and in the striatum by 53 and 68%, respectively). In diabetic animals, IDE protein level was increased in the liver (by 36%) and in the striatum (by 42%) while in the brain cortex and hippocampus it was 20-30% lower than in control animals. No significant IDE protein changes were observed in the kidney of diabetic rats. These data testify that ageing and diabetes are accompanied by a deficit of IDE in the brain structures where accumulation of Aβ was reported in AD patients, which might be one of the factors predisposing to development of the sporadic form of AD in the elderly, and especially in diabetics.