A closer look at the role of insulin for the regulation of male reproductive function

Oghbaei, Hajar; Hamidian, Gholamreza; Sadigh‐Eteghad, Saeed; Ziaee, Mojtaba; Mahmoudi, Javad

doi:10.1016/j.ygcen.2020.113643

Cited by 10 publications

(5 citation statements)

References 142 publications

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“…Insulin plays an important role in sperm capacitation and spermatogenesis 39 . Insulin regulates male reproductive function by acting directly on gonadal cells 40 or affecting function of the hypothalamic‐pituitary‐gonadal (HPG) axis 41 . Studies have demonstrated expression of insulin and its receptors in testes (Leydig and Sertoli cells), and spermatozoa 42,43 .…”

Section: Discussionmentioning

confidence: 99%

Leptin promotes proliferation of human undifferentiated spermatogonia by activating the PI3K/AKT/mTOR pathway

Xin,

Xiaoxuan,

Yixuan

et al. 2024

American J Rep Immunol

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BackgroundMale infertility is a common disease affecting male reproductive health. Leptin is an important hormone that regulates various physiological processes, including reproductive function. However, few experimental studies have been carried out to elucidate the mechanism of leptin's effects on male reproductive function.ObjectiveThe purpose of this study was to investigate the effects of leptin on testicular spermatogenesis and its mechanism, so as to provide potential targets for the treatment of patients with spermatogenic dysfunction.MethodsTesticular tissues were collected from eight prostate cancer patients undergoing surgical castration. GPR125‐positive spermatogonia were isolated by two consecutive magnetic activated cell sorting (MACS), followed by incubation with conditioned medium. To identify the signaling pathway(s) involved in the effects of leptin, undifferentiated spermatogonia were treated with different concentrations of leptin and antagonists of leptin‐related pathways. The proliferative effect of leptin was evaluated by cell counting using a hemocytometer. Expressions of p‐AKT, p‐ERK, p‐STAT, and p‐S6K were determined by western blotting analysis.ResultsLeptin promoted the growth of human GPR125‐positive spermatogonia in a concentration‐dependent manner. The most significant proliferative effect was observed using 100 ng/mL leptin after 6 days of culture. Leptin significantly increased the phosphorylation of STAT3, AKT, and ERK in undifferentiated spermatogonia. Phosphatidylinositol 3‐kinase (PI3K) inhibitor LY294002 inhibited the leptin‐induced activation of AKT, ERK, and downstream S6K. Treatment with the mammalian target of rapamycin (mTOR) inhibitor rapamycin also inhibited S6K phosphorylation. Moreover, both LY294002 and rapamycin were found to inhibit the leptin‐induced proliferation of undifferentiated spermatogonia. These results suggested that the leptin‐induced proliferation of GPR125‐positive spermatogonia was dependent on the PI3K/AKT/mTOR pathway. Further exploration of proliferation and apoptotic markers suggested that leptin may alleviate cell apoptosis by regulating the expression of Bax and FasL.ConclusionsA certain concentration of leptin (25∼100 ng/mL) could promote proliferation of undifferentiated spermatogonia, which was mediated by PI3K/AKT/mTOR pathway.

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Section: Discussionmentioning

confidence: 99%

Leptin promotes proliferation of human undifferentiated spermatogonia by activating the PI3K/AKT/mTOR pathway

Xin,

Xiaoxuan,

Yixuan

et al. 2024

American J Rep Immunol

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“…In addition to controlling metabolic processes and functioning as a neuroprotector, insulin, such as other peptides of the insulin group, plays an important role in the regulation of the functioning of the neuroendocrine and endocrine systems. This is due to the fact that both peripheral and central links of the hypothalamic-pituitary system are targets for insulin, since they contain all the main components of the insulin signaling system [ 347 , 348 ].…”

Section: Intranasal Insulin and The Gonadal And Thyroid Systemsmentioning

confidence: 99%

“…INSR, as well as the other components of the insulin system, are present in the testes and ovaries, and from the embryonic stage [ 347 , 349 , 350 ], and this indicates participation of insulin not only in the regulation of reproductive functions but also in gonadogenesis and sex-specific development [ 347 , 348 ]. It is interesting to note that small amounts of insulin are synthesized in the testes, which indicates its inherent functions as a testicular auto- and paracrine regulator [ 351 ].…”

Section: Intranasal Insulin and The Gonadal And Thyroid Systemsmentioning

confidence: 99%

Hot Spots for the Use of Intranasal Insulin: Cerebral Ischemia, Brain Injury, Diabetes Mellitus, Endocrine Disorders and Postoperative Delirium

Zorina

Derkach

2023

IJMS

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A decrease in the activity of the insulin signaling system of the brain, due to both central insulin resistance and insulin deficiency, leads to neurodegeneration and impaired regulation of appetite, metabolism, endocrine functions. This is due to the neuroprotective properties of brain insulin and its leading role in maintaining glucose homeostasis in the brain, as well as in the regulation of the brain signaling network responsible for the functioning of the nervous, endocrine, and other systems. One of the approaches to restore the activity of the insulin system of the brain is the use of intranasally administered insulin (INI). Currently, INI is being considered as a promising drug to treat Alzheimer’s disease and mild cognitive impairment. The clinical application of INI is being developed for the treatment of other neurodegenerative diseases and improve cognitive abilities in stress, overwork, and depression. At the same time, much attention has recently been paid to the prospects of using INI for the treatment of cerebral ischemia, traumatic brain injuries, and postoperative delirium (after anesthesia), as well as diabetes mellitus and its complications, including dysfunctions in the gonadal and thyroid axes. This review is devoted to the prospects and current trends in the use of INI for the treatment of these diseases, which, although differing in etiology and pathogenesis, are characterized by impaired insulin signaling in the brain.

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“…IR may also cause oxidative stress, negatively impacting sperm quality and fertilization capacity. 121 Furthermore, IR can contribute to the development of metabolic syndrome, which is associated with an increased risk of male infertility. Metabolic syndrome can negatively affect semen quality and impair testicular function.…”

Section: Insulin Resistance and Ovarymentioning

confidence: 99%

Insulin Resistance in Multiple Organs and Systems

Andrade

Oliveira

Bittencourt

et al. 2023

Preprint

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Insulin resistance (IR) is a biological response to insulin stimulation in target tissues. IR alters glucose metabolism, resulting in increased insulin production by beta-cells. The primary condition associated with IR is obesity, which is often caused by environmental factors, particularly diet. Objective: To describe IR in various organs and present a signaling pathway project. Methods: The PubMed database was used to search for IR review publications. The referenced data for the signaling pathway were selected by aggregating references from the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. A signaling pathway was designed based on IR research manuscripts, which show various mechanisms involved. The KEGG server was used to explore protein-protein interactions and create a signaling pathway diagram. The signaling path was mapped using PathVisio software, adapted to the model of the KEGG PATHWAY Database: https://www.genome.jp/pathway/map04930. Results: Articles featuring the terms “insulin resistance” and “signaling pathway” were selected from the PubMed database. Based on validated research articles, well-founded pathways were chosen and a representative description of these pathways was achieved. Reproduction contigs from the KEGG database projected the signaling pathway of biomolecules leading to IR. Thus, the interaction between multiple mechanisms releases factors that contribute to the development of IR. Conclusion: The interaction between multiple mechanisms and molecular interactions are important factors in the development of IR in various organs and systems.

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A closer look at the role of insulin for the regulation of male reproductive function

Cited by 10 publications

References 142 publications

Leptin promotes proliferation of human undifferentiated spermatogonia by activating the PI3K/AKT/mTOR pathway

Leptin promotes proliferation of human undifferentiated spermatogonia by activating the PI3K/AKT/mTOR pathway

Hot Spots for the Use of Intranasal Insulin: Cerebral Ischemia, Brain Injury, Diabetes Mellitus, Endocrine Disorders and Postoperative Delirium

Insulin Resistance in Multiple Organs and Systems

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