The molecular mechanism behind insulin protective effects on testicular tissue of hyperglycemic rats

Aeeni, Mahsa; Razi, Mazdak; Alizadeh, AliReza; Alizadeh, Abolfath

doi:10.1016/j.lfs.2021.119394

Cited by 7 publications

(4 citation statements)

References 46 publications

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“…However, in patients with type 2 diabetes and obesity, abnormal glucose metabolism and insulin resistance are more prevalent, and these conditions may lead to decreased testosterone levels. Disorders of energy metabolism and persistently high glucose levels can disrupt normal hormonal regulation and synthesis mechanisms (Aeeni et al, 2021; Sepu et al, 2021). This phenomenon reveals the effect of abnormal glucose metabolism on testosterone synthesis, and GSD can regulate glucose metabolism in KYDS states to maintain normal testosterone levels and HPG axis function.…”

Section: Discussionmentioning

confidence: 99%

“…Disorders of energy metabolism and persistently high glucose levels can disrupt normal hormonal regulation and synthesis mechanisms (Aeeni et al, 2021;Sepu et al, 2021). This phenomenon reveals the effect of abnormal glucose metabolism on testosterone synthesis, and GSD can regulate glucose metabolism in KYDS states to maintain normal testosterone levels and HPG axis function.…”

Section: Amino Acid Metabolismmentioning

confidence: 99%

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Integrated untargeted and targeted testicular metabolomics to reveal the regulated mechanism of Gushudan on the hypothalamic‐pituitary‐gonadal axis of kidney‐yang‐deficiency‐syndrome rats

Lou,

Liang,

Xin

et al. 2024

Biomedical Chromatography

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Modern studies have shown that neuroendocrine disorders caused by the dysfunction of the hypothalamic‐pituitary‐gonadal (HPG) axis are one of the important pathogenetic mechanisms of kidney‐yang‐deficiency‐syndrome (KYDS). The preventive effect of Gushudan on KYDS has been reported, but its regulatory mechanisms on the HPG axis have not been elucidated. In this study, we developed an integrated untargeted and targeted metabolomics analysis strategy to investigate the regulatory mechanism of Gushudan on the HPG axis in rats with KYDS. In untargeted metabolomics, we screened 14 potential biomarkers such as glycine, lysine, and glycerol that were significantly associated with the HPG axis. To explore the effect of changes in the levels of potential biomarkers on KYDS, all of them were quantified in targeted metabolomics. With the quantitative results, correlations between potential biomarkers and testosterone, a functional indicator of the HPG axis, were explored. The results showed that oxidative stress, inflammatory response, and energy depletion, induced by metabolic disorders in rats, were responsible for the decrease in testosterone levels. Gushudan improves metabolic disorders and restores testosterone levels, thus restoring HPG axis dysfunction. This finding elucidates the special metabolic characteristics of KYDS and the therapeutic mechanism of Gushudan from a new perspective.

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Section: Discussionmentioning

confidence: 99%

Section: Amino Acid Metabolismmentioning

confidence: 99%

Integrated untargeted and targeted testicular metabolomics to reveal the regulated mechanism of Gushudan on the hypothalamic‐pituitary‐gonadal axis of kidney‐yang‐deficiency‐syndrome rats

Lou,

Liang,

Xin

et al. 2024

Biomedical Chromatography

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“…Furthermore, reduced testicular specific heat shock protein‐70‐2 (HSP70‐2) has been reported following high‐intensity training (Matos et al, 2019). Considering this protein specific role in response to heat and oxidative stress conditions (Afiyani et al, 2014), as well as in DNA packing process (Aeeni et al, 2021), reduced Hsp70 in excessive exercise conditions can be another cause of spermatogenesis arrest.…”

Section: Effect Of Sport On Spermatogenesismentioning

confidence: 99%

Influence of physical activity on male fertility

et al. 2022

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Infertility is a worldwide issue impacting 15% of couples' population. Male‐related infertility results in almost 50% of these cases. Considering lifestyle factors associated with infertility, here in this literature review article, we aimed to discuss training/sport effects on male‐related infertility. Regarding this issue, human and animal model studies related to the subject were gathered and analysed. Exercise is well known as a general improving factor, however, excessive exercise can result in male infertility due to reduced hypothalamus–pituitary–gonadal axis (HPT) function, increased oxidative stress and chronic inflammation. Consequently, these underlying impacts result in a low testosterone production, and reduced semen quality, and can lead to infertility. In contrast, it has been revealed that exercise can improve male fertility status in lifestyle‐induced infertility condition such as obesity and diabetes. Indeed, exercise, by increasing testicular antioxidant defence, reducing pro‐inflammatory cytokines level and enhancing the steroidogenesis process, leads to improved spermatogenesis and semen quality in lifestyle‐induced infertility. In fact, it seems that individual health status as well as exercise volume, intensity and duration are effective‐involved co‐factors that influence the impact that exercise will promote on male fertility. Regarding these findings, it is important to study exercise different impacts in further clinical trials in order to generate preservative guidelines for exercise and also considering exercise as a treatment option in lifestyle‐induced disease management.

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“…Conspicuously, normoglycemic animals were used in the present study protocol in order to delineate the actions of linagliptin beyond its glucose-modulating competence. This is particularly imperative in the sense that hyperglycemia in animals has been associated with testicular damage in vivo [ 32 ]. Similar experimental approaches have been adopted in normoglycemic rodents, such as the animal models of kidney damage and inflammatory bowel disease, and the Aβ42-induced Alzheimer’s model [ 27 , 28 , 29 ].…”

Section: Introductionmentioning

confidence: 99%

Repositioning Linagliptin for the Mitigation of Cadmium-Induced Testicular Dysfunction in Rats: Targeting HMGB1/TLR4/NLRP3 Axis and Autophagy

et al. 2022

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Cadmium, a ubiquitous environmental toxicant, disrupts testicular function and fertility. The dipeptidyl peptidase-4 inhibitor linagliptin has shown pronounced anti-inflammatory and anti-apoptotic features; however, its effects against cadmium-evoked testicular impairment have not been examined. Herein, the present study investigated targeting inflammation, apoptosis, and autophagy by linagliptin for potential modulation of cadmium-induced testicular dysfunction in rats. After 60 days of cadmium chloride administration (5 mg/kg/day, by gavage), testes, epididymis, and blood were collected for analysis. The present findings revealed that linagliptin improved the histopathological lesions, including spermatogenesis impairment and germ cell loss. Moreover, it improved sperm count/motility and serum testosterone. The favorable effects of linagliptin were mediated by curbing testicular inflammation seen by dampening of HMGB1/TLR4 pathway and associated lowering of nuclear NF-κBp65. In tandem, linagliptin suppressed the activation of NLRP3 inflammasome/caspase 1 axis with consequent lowering of the pro-inflammatory IL-1β and IL-18. Jointly, linagliptin attenuated testicular apoptotic responses seen by Bax downregulation, Bcl-2 upregulation, and suppressed caspase 3 activity. With respect to autophagy, linagliptin enhanced the testicular autophagy flux seen by lowered accumulation of p62 SQSTM1 alongside upregulation of Beclin 1. The observed autophagy stimulation was associated with elevated AMPK (Ser487) phosphorylation and lowered mTOR (Ser2448) phosphorylation, indicating AMPK/mTOR pathway activation. In conclusion, inhibition of testicular HMGB1/TLR4/NLRP3 pro-inflammatory axis and apoptosis alongside stimulation of autophagy were implicated in the favorable actions of linagliptin against cadmium-triggered testicular impairment.

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The molecular mechanism behind insulin protective effects on testicular tissue of hyperglycemic rats

Cited by 7 publications

References 46 publications

Integrated untargeted and targeted testicular metabolomics to reveal the regulated mechanism of Gushudan on the hypothalamic‐pituitary‐gonadal axis of kidney‐yang‐deficiency‐syndrome rats

Integrated untargeted and targeted testicular metabolomics to reveal the regulated mechanism of Gushudan on the hypothalamic‐pituitary‐gonadal axis of kidney‐yang‐deficiency‐syndrome rats

Influence of physical activity on male fertility

Repositioning Linagliptin for the Mitigation of Cadmium-Induced Testicular Dysfunction in Rats: Targeting HMGB1/TLR4/NLRP3 Axis and Autophagy

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