Fig 1 - available via license: Creative Commons Attribution 4.0 International
Content may be subject to copyright.
Representative histological images of cross-sectional gastrocnemius muscle, stained with hematoxylin and eosin. Scale bars: 50 μm.
Source publication
Regular resistance exercise induces skeletal muscle hypertrophy and improvement of glycemic control in type 2 diabetes patients. Administration of dehydroepiandrosterone (DHEA), a sex steroid hormone precursor, increases 5α-dihydrotestosterone (DHT) synthesis and is associated with improvements in fasting blood glucose level and skeletal muscle hyp...
Citations
... Several studies assessed the effect of PA alone with these hormones. An increase in dihydrotestosterone (i.e., androgen metabolite) was observed following PA and more precisely resistance training [69]. For estrogens, a meta-analysis concluded that PA reduced estradiol body concentrations but also positively influenced SHBG (sex hormone binding globulin), a hormonal regulator that reduces hormone activity [70]. ...
Obesity affects nearly 660 million adults worldwide and is known for its many comorbidities. Although the phenomenon of obesity is not fully understood, science regularly reveals new determinants of this pathology. Among them, persistent organic pollutants (POPs) have been recently highlighted. Mainly lipophilic, POPs are normally stored in adipose tissue and can lead to adverse metabolic effects when released into the bloodstream. The main objective of this narrative review is to discuss the different pathways by which physical activity may counteract POPs’ adverse effects. The research that we carried out seems to indicate that physical activity could positively influence several pathways negatively influenced by POPs, such as insulin resistance, inflammation, lipid accumulation, adipogenesis, and gut microbiota dysbiosis, that are associated with the development of obesity. This review also indicates how, through the controlled mobilization of POPs, physical activity could be a valuable approach to reduce the concentration of POPs in the bloodstream. These findings suggest that physical activity should be used to counteract the adverse effects of POPs. However, future studies should accurately assess its impact in specific situations such as bariatric surgery, where weight loss promotes POPs’ blood release.
... Several studies assessed the effect of PA alone with these hormones. An increase of dihydrotestosterone (i.e., androgen metabolite) is observed following PA and more precisely resistance training [66]. For estrogens, a meta-analysis concluded that PA reduces estradiol body concentrations but also positively influenced SHBG (Sex Hormone Binding Globulin), a hormonal regulator who reduces hormones activity [67]. ...
Obesity affects nearly 660 million adults worldwide and is known for its many comorbidities. Although the phenomenon of obesity is not fully understood, science regularly reveals new determinants of this pathology. Among them, the persistent organic pollutants (POPs) have been recently highlighted. Mainly lipophilic, POPs are normally stored in adipose tissue and can lead to adverse metabolic effects when released into the bloodstream. The main objective of this narrative review is to discuss the different pathways by which physical activity may counteract POPs adverse effects. The research that we carried out seems to indicate that physical activity could positively influence several pathways negatively influenced by POPs, such as insulin resistance, inflammation, lipid accumulation, adipogenesis and gut microbiota dysbiosis that are associated with the development of obesity. This review also indicates how, through the controlled mobilization of POPs, physical activity could be a valuable approach to reduce the concentration of POPs in the bloodstream. These findings suggest that physical activity should be used to counteract the adverse effects of POPs. However, future studies should accurately assess its impact in specific situations such as bariatric surgery where weight loss promotes POPs blood release.
... Multiple muscles were removed; soleus (SOL), gastrocnemius (GSN), and plantaris muscles. They were blotted dry with filter paper and weighed on an analytical scale and the body weights of the rats were also measured as mentioned in 2.3 section (Bonetto et al., 2015), (Horii et al., 2016). ...
Objective: Telmisartan is an angiotensin receptor blocker (ARB) that specifically blocks angiotensin II type-1 receptors (AT1R). Telmisartan has been proven to have antidiabetic effects via a variety of mechanisms, and it can be utilized in some diabetic patients due to its dual benefit for hypertensive patients with type 2 DM (T2DM) and when the other oral antidiabetic medications are intolerable or contraindicated. However, its precise underlying hypoglycemic mechanism is still obscure.
Aim of work: We sought to establish a link between telmisartan administration and myostatin expression in skeletal muscles of T2DM rat model as a potential hypoglycemic mechanism of telmisartan.
Materials and Methods: 32 male albino rats were included in the study; 8 rats served as controls (group I). T2DM was inducted in the other 24 rats, which were then randomly subdivided into 3 groups (8 in each): (group II) the Diabetic group and (groups III and IV) which were treated with either telmisartan (8 mg/kg/day) or metformin (250 mg/kg/day) respectively via oral gavage for a 4-week period.
Results: Telmisartan administration resulted in a significant improvement in OGTT, HOMA-IR, glucose uptake, and muscle mass/body ratios in Telmisartan group as compared to Diabetic group ( p < 0.05). Additionally, telmisartan induced a significant boost in adiponectin and IL-10 serum levels with a substantial drop in TNF-α and IL-6 levels in Telmisartan group compared to diabetic rats ( p < 0.05). Moreover, telmisartan significantly boosted SOD and GSH, and decreased MDA levels in the skeletal muscles of telmisartan group. Furthermore, a significant downregulation of myostatin and upregulation of insulin receptor, IRS-1, and IRS-3 genes in the skeletal muscles of Telmisartan group were also detected. Histologically, telmisartan attenuated the morphological damage in the skeletal muscle fibers compared to diabetic rats, as evidenced by a considerable decrease in the collagen deposition area percentage and a reduction in NF-kB expression in the muscle tissues of group III.
Conclusion: Telmisartan administration dramatically reduced myostatin and NF-kB expressions in skeletal muscles, which improved insulin resistance and glucose uptake in these muscles, highlighting a novel antidiabetic mechanism of telmisartan in treating T2DM.
... Habitual resistance exercise increases muscle mass, androgen hormone, and steroidogenic enzyme expression levels in elderly adults, and increased muscle DHT secretion is correlated with muscle hypertrophy [20]. Furthermore, our previous study using rodent models showed that resistance training induced muscle hypertrophy and improved glycemic control; however, treatment with a DHT inhibitor suppressed these effects [21]. Therefore, the resistance training-induced secretion of androgen hormones is an important compound related to muscle mass and cardiometabolic parameters. ...
... Our recent study in rats showed that acute resistance exercise-induced activation of the Akt/mTOR/p70S6K signaling pathway with an increase in muscle DHT production was attenuated through the pre-administration of a DHT synthase inhibitor [35]. Furthermore, continuous administration of DHT synthase inhibitors during regular resistance exercise suppresses muscle hypertrophy [21]. Additionally, habitual resistance exercise in the elderly increases the expression of steroidogenic enzymes in skeletal muscle and muscle DHT levels, and muscle DHT is correlated with muscle cross-sectional area [20]. ...
Resistance training and Dioscorea esculenta intake have a positive effect on muscle. Therefore, we aimed to determine whether 12-week Dioscorea esculenta intake combined with resistance exercise more effectively improves muscle quantity, quality, and cardiometabolic parameters in healthy middle-aged and older adults. This study is a double-blind trial with 66 volunteers (21 males/45 females; age 53 ± 5 years; body weight 61 ± 11 kg; BMI 24 ± 4 kg) who were randomly divided into four groups: sedentary-control with placebo (Sed and PL) or Dioscorea (Sed and Dio) and resistance training with placebo (RT and PL) or Dioscorea (RT and Dio). Resistance training sessions using elastic bands were performed 3 days/week for a 12-week period. Dioscorea esculenta tablets were ingested at 2000 mg/day once per day. The RT and Dio group showed greater improvements in the femoris muscle’s thickness, echo intensity for the rectus femoris (index of muscle quality), and the five times sit-to-stand test compared to that of the Sed and PL group; the echo intensity in the RT and Dio group further improved compared to those in the Sed and Dio, and RT and PL groups (p < 0.05). The circulating levels of C1q (a potential biomarker of muscle fibrosis) in the RT and Dio group were significantly lower than those in the Sed and PL, and Sed and Dio groups (p < 0.05). Chronic Dioscorea esculenta intake combined with low-intensity resistance exercise may more effectively improve muscle quantity and quality indices in healthy middle-aged and older adults.
... (a) Skeletal muscle stores glucose as glycogen through the translocation of glucose transporter type-4 via insulin signals (12). (b) Testosterone may be critical to skeletal muscle glucose metabolism, as it has been reported that elevated muscular 5α-dihydrotestosterone may contribute to the improvement of hyperglycemia in T2D rats (13), and higher testosterone concentrations and muscle mass were associated with improved glucose metabolism in children (11). (c) Forkhead box class O transcription factors regulate glucose metabolism and markers of inflammation in skeletal muscle (14). ...
Purpose:
To assess the relationship between fat-free mass (FFM) and glucose metabolism in children 0-18 years of age.
Methods:
We performed a systematic review of the literature on Medline/PubMed, SinoMed, Embase, and the Cochrane Library using the PRISMA 2020 guidelines to 12 October 2021; this encompassed observational studies in which the relationship between FFM and glucose metabolism was assessed. Correlation coefficient (r), regression coefficient (β), and odds ratio (OR) values in the studies were extracted and recorded as the primary data. "Agency for Healthcare Research and Quality" quality-assessment forms recommended for cross-sectional/prevalence studies were applied to evaluate the quality of the selected studies, and we executed R software to combine the pooled data.
Results:
We included eight studies comprising 13,282 individuals, five of which involved the assessment of the relationship between FFM and blood glucose, and four on the relationship between FFM and insulin resistance (IR). Our results showed that FFM was significantly associated with fasting plasma insulin levels (r = 0.34, 95% CI: 0.30-0.39, P < 0.001). Due to high heterogeneity or insufficient quantity of data, the studies of the relationship between FFM and fasting plasma glucose, HOMA-IR, or HbA1c were not congruent, and were therefore not suitable for meta-analysis.
Conclusion:
Our results indicated that FFM was significantly associated with fasting plasma insulin levels. As far as we have determined, this is the first-ever systematic review and meta-analysis of the associations between FFM and glucose metabolism in children and adolescents; and our results thus provide novel information to fill a gap in the literature in this area.
Systematic review registration:
https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020150320, PROSPERO CRD42020150320.
... This theory is somewhat intertwined with the concept that androgen promotion capability increases with training and decreases with detraining, especially given the potential upregulation of 5α-reductase with a chronic training load. 19 Further support comes from rodent studies, which have shown a relationship between skeletal muscle mass and DHT concentration, 2 and work showing a rise in baseline serum DHT among chronically trained aged males. 20 As such, it would be informative to monitor changes in DHT concentration across training cycles. ...
Purpose:
To establish if training volume was associated with androgen baselines and androgen responsiveness to acute exercise.
Methods:
During a "high-volume" training phase, 28 cyclists (14 men and 14 women) undertook oxygen-uptake and maximal-work-capacity testing. Two days later, they completed a repeat-sprint protocol, which was repeated 3 weeks later during a "low-volume" phase. Blood and saliva samples were collected before and after (+5 and +60 min) the repeat-sprint protocol. Blood was assayed for total testosterone (TT), free testosterone (FT), and dihydrotestosterone (DHT) and saliva, for testosterone and DHT.
Results:
Pretrial TT, FT, and DHT concentration was greater for males (P < .001, large effect size differences), and in both genders TT, DHT, and saliva for DHT was higher during high-volume loading (moderate to large effect size). Area-under-the-curve analysis revealed larger TT, FT, and DHT responses to the repeat-sprint protocol among females, and high-volume training was linked to larger TT, DHT, and saliva for DHT responses (moderate to large effect size). Baseline TT and FT correlated with oxygen uptake and work capacity in both genders (P < .05).
Conclusion:
DHT showed no acute performance correlation but was responsive to volume of training, particularly in females. This work informs on timelines and relationships of androgenic biomarkers in males and females across different training loads, adding to the complexity that should be considered in interpretation thereof. The authors speculate that testosterone may impact acute performance via behavioral mechanisms of motivation and attention; DHT, via training volume-induced androgenic promotion, may facilitate long-term adaptive changes, especially for females.
... Chronic resistance exercise induced muscle hypertrophy and reduced fasting glucose, glycosylated hemoglobin, and the insulin resistance index in type 2 diabetes patients in randomized controlled studies (Arora et al., 2009;Bacchi et al., 2012;Dunstan et al., 2002;Kadoglou et al., 2013;Sigal et al., 2007). As part of the molecular mechanism underlying the effects of chronic resistance exercise, an increase in the uptake and utilization of glucose, via increases in the transcription and translocation of glucose transporter 4 (GLUT-4) in the skeletal muscle, contributes to the improvement of glycemic control (Horii et al., 2016;Kim et al., 2015). ...
... Resistance training was performed 3 days a week for 8 weeks using a climbing ladder (length: 1.1 m, grid step: 2.0 cm, and inclination: 80°) as described in a previous study (Horii et al., 2016;Hornberger & Farrar, 2004). The OLETF-RT group climbed the ladder for three sets of four repetitions each, and the rats were allowed to rest for 1 min between each set. ...
... Western blotting analysis was performed as reported previously (Horii et al., 2016(Horii et al., , 2020Sato et al., 2017). Briefly, ...
Chronic resistance exercise induces improved hyperglycemia in patients with type 2 diabetes mellitus. Musclin, a muscle-derived secretory factor, is involved in the induction of insulin resistance via the downregulation of the glucose transporter-4 (GLUT-4) signaling pathway in skeletal muscles. However, whether musclin affects the mechanism of resistance exercise remains unclear. This study aimed to clarify whether decreased muscle-derived musclin secretion in chronic resistance exercise is involved in the improvement of insulin resistance via the GLUT-4 signaling pathway in rats with type 2 diabetes. Male, 20-week-old, Otsuka Long-Evans Tokushima Fatty (OLETF) rats, a type 2 diabetes model, were randomly divided into two groups: sedentary control (OLETF-Con) and chronic resistance exercise (OLETF-RT; climbing a ladder three times a week on alternate days for 8 weeks), whereas Long-Evans Tokushima Otsuka rats were used as the nondiabetic sedentary control group. OLETF-Con rats showed increased fasting glucose levels, decreased insulin sensitivity index (QUICKI), muscle GLUT-4 translocation, and protein kinase B (Akt) phosphorylation, and concomitantly increased muscle musclin expression. In contrast, OLETF-RT rats significantly reduced muscle musclin expression, improved hyperglycemia, and QUICKI through an accelerated muscle GLUT-4/Akt signaling pathway. Moreover, chronic resistance exercise-induced reduction of muscle musclin was correlated with changes in fasting glucose, QUICKI, GLUT-4 translocation, and Akt phosphorylation. These findings suggest that the reduction in muscle-derived musclin production by chronic resistance exercise may be involved in improved insulin resistance in rats with type 2 diabetes.
... 15,16 The levels of androgens (DHEA, testosterone, and DHT) and steroidogenic enzymes (3β-HSD, 17β-HSD, and 5α-reductase) in muscles were reported to be decreased in type 2 diabetic rats in comparison to the respective levels in healthy control rats 17,18 ; chronic resistance training restored steroidogenesis in the muscle. 19,20 Interestingly, chronic administration of a 5α-reductase inhibitor, which suppresses the conversion of testosterone to DHT, attenuated the beneficial effects of resistance training-induced skeletal muscle hypertrophy, and improvement of hyperglycemia in type 2 diabetic rats. 20 Moreover, chronic DHT injection activated the phosphorylation of muscle mTOR/p70S6K. ...
... 19,20 Interestingly, chronic administration of a 5α-reductase inhibitor, which suppresses the conversion of testosterone to DHT, attenuated the beneficial effects of resistance training-induced skeletal muscle hypertrophy, and improvement of hyperglycemia in type 2 diabetic rats. 20 Moreover, chronic DHT injection activated the phosphorylation of muscle mTOR/p70S6K. 21,22 Additionally, DHEA administration-induced elevation of muscle Akt phosphorylation and GLUT4 translocation in diabetic rats was blocked by a 5α-reductase inhibitor. ...
... described in previous studies. 20,26 The rats in the resistance exercise groups climbed the ladder for three sets of four repetitions each, and were allowed to rest between the sets for 1 min. This exercise protocol is used widely as a resistance exercise model for animals and induces significant muscle hypertrophy. ...
Effects of increase in muscle 5α‐dihydrotestosterone (DHT) levels caused by resistance exercise on regulation of mammalian target of rapamycin (mTOR)‐ and glucose transporter 4 (GLUT4)‐signaling pathways in type 2 diabetic rats were assessed. Twenty‐week‐old type 2 diabetic rats were randomly divided into the resting control, immediately, 1 hour, or 3 hours after resistance exercise, with or without the pretreatment of 5α‐reductase inhibitor. Immediately or 1 hour after exercise, levels of 5α‐reductase and DHT as well as phosphorylation levels of AMP‐activated protein kinase (AMPK), TBC1 domain family member 1 (TBC1D1), and protein kinase B (Akt) in muscle were significantly elevated. Phosphorylation of muscle Akt substrate of 160 kDa (AS160) and translocation levels of GLUT4 at 1 and 3 hours after resistance exercise were significantly elevated. Additionally, resistance exercise significantly activated the phosphorylation of muscle mTOR immediately, and at 1 and 3 hours and of p70 ribosomal S6 kinase (p70S6K) at 1 and 3 hours. However, pretreatment with the 5α‐reductase inhibitor significantly attenuated the exercise‐induced activation of Akt/mTOR/p70S6K and Akt/AS160/GLUT4 signaling, but did not affect AMPK/TBC1D1/GLUT4 signaling. These findings suggest that resistance exercise‐induced increase in muscle DHT synthesis may contribute to activation of Akt/mTOR/p70S6K‐ and Akt/AS160/GLUT4 signaling pathways in type 2 diabetic rats.
... Introduction A ndrogen hormones such as dehydroepiandrosterone (DHEA), testosterone, and 5a-dihydrotestosterone (DHT) have many important roles, including regulation of muscle protein synthesis, (1)(2)(3) energy metabolism, (4,5) bone turnover, (6) immune function, (7) motor skills, (8) and behavioral motivation and condition. (9) Therefore, androgen hormones are important compounds related to body composition and exercise performance in athletes. ...
... Additionally, our recent studies showed that resistance training enhanced the serum and muscle DHEA, free testosterone, and DHT levels, and that the elevation of muscle androgen hormone levels were associated with training-induced increases in muscle mass and strength in healthy older men (19) and type 2 diabetic rats. (1) Moreover, androgen hormone treatment augmented the resistance training-induced increases in muscle mass and strength in normal men (16) and older patients, (20) respectively. However, the effects of the combination of Dioscorea esculenta intake and resistance training on muscle hypertrophy and strength in athletes remain unclear. ...
... Treatment with androgen hormones is well known to increase muscle mass and strength in human and animal studies, (1)(2)(3)15,16,19) whereas treatment with supraphysiologic doses of androgen hormones may cause adverse effects such as increased risks of cardiac death (25,26) and cancer. (27,28) In our recent study using diabetic rats, chronic Dioscorea esculenta supplementation, which induced increases in the serum and muscle levels of DHEA and DHT, did not cause adverse effects or toxicities. ...
Androgen hormones are important compounds related to body composition and exercise performance in athletes. The intake of Dioscorea esculenta, known as lesser yam, contains diosgenin and resistance training have been shown to normalize the secretion of androgen hormones. This study aimed to clarify the level of androgen hormone secretion and the effects of Dioscorea esculenta intake with resistance training on muscle hypertrophy and strength in athletes. First, in a cross-sectional study, we compared the serum androgen hormone [dehydroepiandrosterone (DHEA), testosterone, and 5α-dihydrotestosterone (DHT)] levels between sprint athletes (n = 15) and non-athletes (n = 15). Second, in an 8-week intervention study, sprint athletes were randomly divided into 2 groups: resistance training with placebo (n = 8) or with Dioscorea esculenta (2,000 mg/day) intake (n = 7). The serum DHEA, free testosterone, and DHT levels were lower in athletes than in non-athletes. Dioscorea esculenta intake combined with resistance training increased the arm fat-free mass, the 1 repetition maximum of deadlift and snatch, and the serum DHEA, free testosterone, and DHT levels, compared with resistance training and placebo intake. The results suggested that Dioscorea esculenta intake combined with resistance training has further effects on muscle hypertrophy and strength in athletes by restoring secretion of androgen hormones.
... Rui Liu et al found that DHT modulates the proliferation and adhesion of endothelial progenitor cells via PI3K/Akt pathway, for DHT directly phosphorylates Akt [46]. In male type 2 diabetic rat, increased DHT in skeletal muscle in response to resistance training improves the hyperglycemia and insulin sensitivity index by the GLUT-4 translocation and phosphorylation of Akt [47]. In this research, we found that Ar was mostly localized in the extranuclear compartment of MIN6 cells without DHT. ...
Glucagon-like peptide-1 receptor (GLP-1R) is an important pharmacological target for type 2 diabetes mellitus because it maintains glucose homeostasis and promotes β cell proliferation. Androgen is suggested not only to regulate hypothalamic-pituitary-gonadal axis but also to affect metabolism. In this study, Glp1r mRNA was found widely expressed in normal male mice and its levels were positively correlated with the serum testosterone (T) concentrations. Using mouse insulinoma 6 (MIN6) cells, which highly express GLP-1R, we observed GLP-1R was upregulated both at transcriptional and protein levels induced by dihydrotestosterone (DHT) and was downregulated by androgen receptor inhibitor ARN-509 or small interfering RNA (siRNA) targeting Glp1r mRNA. In normal C57BL/6 mice and db/db mice, Glp1r mRNA levels in the pancreases increased in the DHT treatment group and decreased in the ARN-509 treatment group. And the increased GLP-1R expression had insulinotropic function both in vitro and in vivo. Further analysis showed that the androgen receptor (Ar) located in the cytosol of MIN6 cells and translocated to the nucleus after DHT treatment. In addition, we found that there was an Ar motif in the promoter region of the Glp1r gene. Further studies revealed that the translocated DHT/Ar complex from the cytosol to the nucleus bound to the Ar motif of the Glp1r gene and upregulated gene transcription. Taken together, the widely expressed GLP-1R was positively regulated by androgen under physiological condition and in diabetic models at the transcriptional level.
