scholarly journals Testicular Metabolic Reprogramming in Neonatal Streptozotocin-Induced Type 2 Diabetic Rats Impairs Glycolytic Flux and Promotes Glycogen Synthesis

2015 ◽  
Vol 2015 ◽  
pp. 1-13 ◽  
Author(s):  
L. Rato ◽  
M. G. Alves ◽  
T. R. Dias ◽  
J. E. Cavaco ◽  
Pedro F. Oliveira

Defects in testicular metabolism are directly implicated with male infertility, but most of the mechanisms associated with type 2 diabetes- (T2DM) induced male infertility remain unknown. We aimed to evaluate the effects of T2DM on testicular glucose metabolism by using a neonatal-streptozotocin- (n-STZ) T2DM animal model. Plasma and testicular hormonal levels were evaluated using specific kits. mRNA and protein expression levels were assessed by real-time PCR and Western Blot, respectively. Testicular metabolic profile was assessed by1H-NMR spectroscopy. T2DM rats showed increased glycemic levels, impaired glucose tolerance and hyperinsulinemia. Both testicular and serum testosterone levels were decreased, whereas those of 17β-estradiol were not altered. Testicular glycolytic flux was not favored in testicles of T2DM rats, since, despite the increased expression of both glucose transporters 1 and 3 and the enzyme phosphofructokinase 1, lactate dehydrogenase activity was severely decreased contributing to lower testicular lactate content. However, T2DM enhanced testicular glycogen accumulation, by modulating the availability of the precursors for its synthesis. T2DM also affected the reproductive sperm parameters. Taken together these results indicate that T2DM is able to reprogram testicular metabolism by enhancing alternative metabolic pathways, particularly glycogen synthesis, and such alterations are associated with impaired sperm parameters.

1975 ◽  
Vol 150 (2) ◽  
pp. 153-165 ◽  
Author(s):  
P D Whitton ◽  
D A Hems

1. Net glycogen accumulation was measured in sequentially removed samples during perfusion of the liver of starved streptozotocin-diabetic rats, and shown to be significantly impaired, compared with rates in normal (starved) rats. 2. In perfusions of normal livers with glucose plus C3 substrates, there was an increase in the proportion of glycogen synthetase ‘a’, compared with that in the absence of substrates. This response to substrates, followed in sequential synthesis and enzymic sensitivity in the perfused liver of diabetic rats were reversed by pretreatment in vivo with glucose plus fructose, or insulin. Glucose alone did not produce this effect. 4. Glucose, fructose, insulin or cortisol added to e perfusion medium (in the absence of pretreatment in vivo) did not stimulate glycogen synthesis in diabetic rats. 5. In intact diabetic rats, there was a decline in rates of net hepatic glycogen accumulation, and the response of glycogen synthetase to substrates. The most rapid rates of synthesis were obtained after fructose administration. 6. These results demonstrate that there is a marked inherent impairment in hepatic glycogen synthesis in starved diabetic rats, which can be rapidly reversed in vivo but no in perfusion. Thus hepatic glycogen synthesis does not appear to be sensitive to either the short-term direct action of insulin (added alone to perfusions) of to long-term insulin deprivation in vivo. The regulatory roles of substrates, insulin and glycogen synthetase in hepatic glycogen accumulation are discussed.


2021 ◽  
Vol 2021 ◽  
pp. 1-14
Author(s):  
Hadeel A. Al-Rawaf ◽  
Sami A. Gabr ◽  
Ahmad H. Alghadir

Background. Therapeutic strategies based on herbal plants and diets containing sufficient amounts of antioxidants and essential vitamins are very important factors in treating reproduction and male infertility worldwide. Thus, the aim of this study was to investigate the potential effects of Kaempferia parviflora (KP) on the role of some microRNAs in treated and nontreated infertile rats. In addition, the correlation of expressed microRNAs with sperm count, sperm motility, and sperm viability was identified. The probable use of these microRNAs as a diagnostic marker for predicting the clinical response of infertility to the treatment with KP was also achieved. Methods. In the present study, the potential effects of Kaempferia parviflora (KP) at different doses (140, 280, and 420 mg/kg) for six weeks on male rats with subinfertility were explored. In addition, the effect of KP on the expression of circulating microRNAs and its correlation with the parameters of sexual infertility was identified by performing both in vitro and in vivo assays. In vitro antioxidant activity, sperm functional analysis, serum testosterone, and expression of circulating microRNAs were conducted using colorimetric, ELISA, and real-time RT-PCR analysis, respectively. Results. Kaempferia parviflora (KP) at nontoxic doses of 140–420 mg/kg/day for six weeks significantly improved serum testosterone and epididymal sperm parameters (sperm count, motility, and sperm viability), increased testicular weight, and provided a reduction in the percentage of abnormal spermatozoon in infertile male rats. The expression of miR-328 and miR-19b significantly decreased, and miR-34 significantly increased in infertile rats treated with KP compared to infertile nontreated rats. After six weeks of KP therapy, the change in the expression levels of miRNAs was correlated positively with higher levels of serum testosterone and the measures of epididymal sperm parameters. The respective area under the receiver operating characteristic curve (AUC-ROC) was applied to predict the potential use of miR-328, miR-19b, and miR-34 in the diagnosis of male infertility in treated and nontreated infertile male rats. The data showed that AUC cutoff values of 0.91 for miR-328, 0.89 for miR-19b, and 0.86 for miR34 were the best estimated values for the clinical diagnosis of male rats with infertility. In rats treated with KP for six weeks, AUC cutoff values of 0.76 for miR-328, 0.79 for miR-19b, and 0.81 for miR-34 were the best cutoff values reported for the clinical response of infertility to KP therapy after six weeks. Conclusions. In this study, the improvement of male infertility might proceed via antioxidant and antiapoptotic pathways, which significantly improve spermatogenesis and aphrodisiac properties of males. In addition, the expression of miRNAs, miR-328, miR-34, and miR-19b, in KP-treated and nontreated infertile rats significantly correlated with increased serum testosterone levels and epididymal sperm parameters as well. MicroRNAs, miR-328, miR-34, and miR-19b, might be related to oxidative and apoptotic pathways that proceeded in spermatogenesis. Thus, the use of miRNAs could have a role as diagnostic, therapeutic, and predictive markers for assessing the clinical response of Kaempferia parviflora treatment for six weeks. This may have potential applications in the therapeutic strategies based on herbal plants for male infertility. However, in subsequent studies, the genetic regulatory mechanisms of the expressed miRNAs should be fully characterized.


Andrologia ◽  
2019 ◽  
Vol 51 (8) ◽  
Author(s):  
Maryam Bahmanzadeh ◽  
Mohammad Taghi Goodarzi ◽  
Azam Rezaei Farimani ◽  
Nasibeh Fathi ◽  
Zohreh Alizadeh

2012 ◽  
Vol 302 (4) ◽  
pp. E409-E416 ◽  
Author(s):  
Tienian Zhu ◽  
Ruijing Zhao ◽  
Lizhong Zhang ◽  
Michel Bernier ◽  
Jiankun Liu

The aim of the present study was to examine the effects of pyrrolidine dithiocarbamate (PDTC) on hepatic glycogen synthesis and FoxO1 transcriptional activity in type 2 diabetic rats and the mechanism underlying these effects. Fasting blood glucose and glycogen deposition, together with expressions of two key genes related to gluconeogenesis, were studied in the liver of rats fed a normal diet (NC), high-fat diet (HFD)-induced insulin-resistant rats made type 2 diabetic by a single intraperitoneal injection of streptozotocin (DM), and a DM with intervention of PDTC (DM + PDTC) for 1 wk. The phosphorylation of Akt, GSK-3β, and FoxO1 was assessed in liver extracts of fasted rats by Western blot, whereas indirect immunofluorescence staining was performed to determine the cellular distribution of FoxO1. The DM rats exhibited obvious increases in fasting blood glucose as well as decreased hepatic glycogen content compared with the NC group. Activation of the Akt/GSK-3β pathway and inactivating phosphorylation of FoxO1 were reduced greatly in DM rat livers ( P < 0.01). By contrast, PDTC treatment protected DM rats against high fasting blood glucose and hepatic glycogen deposition loss. PDTC also elicited an increase in Akt/GSK-3β signaling and subsequent inactivation and nuclear export of FoxO1 in DM rat livers, which translated into a significant reduction in the expression of two FoxO1 target genes, phospho enolpyruvate carboxykinase and glucose-6-phosphatase. This study suggests that PDTC enhances hepatic glycogen synthesis, whereas it reduces FoxO1 transcriptional activity in DM rats.


Author(s):  
Zahra Nadi ◽  
Mohammad Bayat ◽  
Hadi Karami ◽  
Mohamad Parastesh ◽  
ParvinDokht Bayat

Adiponectin and its receptors are expressed in the male reproductive system, which play a role in regulating male sex hormones and fertility. Diabetes was induced by Streptozotocin-Nicotinamide (STZ-NA i.p) in rats and after performing the trainings, adiponectin gene expression and its receptors in the testis were evaluated using real time PCR, and blood serum was then used in order to assess FSH, LH and testosterone. The STZ-NA significantly increased the fasting blood glucose, gene expression of adiponectin AdipoR1 in the testicles of diabetic rats. A significant reduction in serum testosterone and LH levels were observed in the diabetic group. Resistance and endurance training decreased blood glucose, adiponectin and AdipoR1 gene, and also increased the serum testosterone and LH levels in diabetic rats. Overall, our data suggest the role played by training in improve expression of adiponectin and AdipoR1 gene by increasing the serum testosterone and LH levels in type 2 diabetic rats.    


2020 ◽  
Vol 47 (1) ◽  
pp. 34-41
Author(s):  
Ali Akbar Rezaei ◽  
Iraj Salehi ◽  
Seyed Asaad Karimi ◽  
Mehdi Rahnama

Objective: The strong antioxidant activity of <i>Commiphora mukul</i> prompted us to conduct the present study to explore whether treatment with <i>C. mukul</i> extract (CME) would have any protective influence on sperm parameters, testosterone levels, and plasma glucose levels in streptozotocin (STZ)-induced diabetic rats.Methods: Male Wistar rats were randomly divided into four groups: control, control animals treated with CME, diabetic animals, and diabetic animals treated with CME. CME extract (300 mg/kg) was administered for 60 days by daily gavage. Diabetes was induced by an intraperitoneal injection of 50 mg/kg STZ. The epididymal sperm count, weight, motility, morphology, viability, and serum testosterone and glucose levels were determined.Results: In the diabetic animals, CME decreased blood glucose levels (<i>p</i><0.05), increased the total sperm count (<i>p</i><0.05), and decreased the proportion of sperm with abnormal morphology (<i>p</i><0.05). Diabetes reduced sperm motility (<i>p</i><0.001), and CME supplementation partially reversed this effect of diabetes (<i>p</i>=0.003). Furthermore, in diabetic animals, CME decreased the proportion of immotile sperm (<i>p</i><0.001). In rats, diabetes caused a significant decrease (<i>p</i><0.05) in serum testosterone levels (F[3, 28]=3.283, <i>p</i>=0.035), but treatment of diabetic animals with CME increased serum testosterone levels.Conclusion: The present study demonstrated that C. mukul possesses proandrogenic activity and exerts a beneficial effect on sperm parameters in diabetic rats.


Author(s):  
Zahra Nadi ◽  
Mohammad Bayat ◽  
Hadi Karami ◽  
Mohamad Parastesh ◽  
ParvinDokht Bayat

Adiponectin and its receptors are expressed in the male reproductive system, which play a role in regulating male sex hormones and fertility. Diabetes was induced by Streptozotocin-Nicotinamide (STZ-NA i.p) in rats and after performing the trainings, adiponectin gene expression and its receptors in the testis were evaluated using real time PCR, and blood serum was then used in order to assess FSH, LH and testosterone. The STZ-NA significantly increased the fasting blood glucose, gene expression of adiponectin AdipoR1 in the testicles of diabetic rats. A significant reduction in serum testosterone and LH levels were observed in the diabetic group. Resistance and endurance training decreased blood glucose, adiponectin and AdipoR1 gene, and also increased the serum testosterone and LH levels in diabetic rats. Overall, our data suggest the role played by training in improve expression of adiponectin and AdipoR1 gene by increasing the serum testosterone and LH levels in type 2 diabetic rats.    


Diabetes ◽  
2018 ◽  
Vol 67 (Supplement 1) ◽  
pp. 643-P ◽  
Author(s):  
YANFEI HAN ◽  
LINDONG LI ◽  
YANJUN LIU ◽  
YOU WANG ◽  
CHUNHUA YAN ◽  
...  

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