Insulin and insulin-like growth factor 1 (IGF-I) are capable of activating similar intracellular pathways. Insulin acts mainly through its own receptor, but can also activate the IGF-I receptor (IGF-IR). The aim of this study was to investigate the involvement of the IGF-IR in the effects of insulin and IGF-I on the membrane potential of immature Sertoli cells in whole seminiferous tubules, as well as on calcium, amino acid, and glucose uptake in testicular tissue of immature rats. The membrane potential of the Sertoli cells was recorded using a standard single microelectrode technique. In calcium uptake experiments, the testes were pre-incubated with (45)Ca(2+), with or without JB1 (1 μg/mL), and then incubated with insulin (100 nM) or IGF-I (15 nM). In amino acid and glucose uptake experiments, the gonads were pre-incubated with or without JB1 (1 μg/mL) and then incubated with radiolabeled amino acid or glucose analogues in the presence of insulin (100 nM) or IGF-I (15 nM). The blockade of IGF-IR with JB1 prevented the depolarising effects of both insulin and IGF-I on membrane potential, as well as the effect of insulin on calcium uptake. JB1 also inhibited the effects of insulin and IGF-I on glucose uptake. The effect of IGF-I on amino acid transport was inhibited in the presence of JB1, whereas the effect of insulin was not. We concluded that while IGF-I seems to act mainly through its cognate receptor to induce membrane depolarisation and calcium, amino acid and glucose uptake, insulin appears to be able to elicit its effects through IGF-IR, in seminiferous tubules from immature rats.
Purpose: To evaluate the accuracy of the uterine artery pulsatility index (PI) for the diagnosis of pubertal onset in girls.Methods: Cross-sectional study of girls with normal pubertal development. Puberty was diagnosed by the presence of Tanner breast development score ≥2. All girls underwent pelvic ultrasound and Doppler imaging of the uterine arteries. We evaluated the uterine artery PI and uterine, endometrial, and ovarian measurements. We used ROC curves with cutoffs determined by Youden index for data analysis.Results: We included 169 girls aged 5-16 years who underwent 202 pelvic ultrasound examinations. Prepubertal girls had a signi cantly higher mean PI (mean, 6.70; SD, 2.15) than girls in initial puberty (mean, 4.14; SD, 1.55) and in late puberty (mean, 2.81; SD, 1.05) (P<0.001 for all comparisons), which re ects a progressive increase in blood ow to the uterus with the progression of puberty. ROC curve analysis showed that the PI was able to identify the onset of puberty with a mean area under the curve of 0.838 (SD, 0.04) (P<0.001), and the PI cutoff point of 5.05 had a sensitivity of 77%, speci city of 85%, positive predictive value (PPV) of 92%, and accuracy of 79%. The combination of PI <5.05 plus uterine volume >3.75 cm³ had a sensitivity of 73%, speci city of 95%, PPV of 97%, and accuracy of 79% to detect initial puberty.Conclusions: The signi cant reduction in the PI during pubertal development combined with increasing uterine volume can be a valuable, highly speci c, noninvasive tool to con rm the onset of puberty.
Background Diabetic kidney disease is the leading cause of end-stage renal disease and is associated with increased morbidity and mortality. This review is an authorized literal translation of part of the Brazilian Diabetes Society (SBD) Guidelines 2021–2022. This evidence-based guideline provides guidance on the correct management of Diabetic Kidney Disease (DKD) in clinical practice. Methods The methodology was published elsewhere in previous SBD guidelines and was approved by the internal institutional Steering Committee for publication. Briefly, the Brazilian Diabetes Society indicated 14 experts to constitute the Central Committee, designed to regulate methodology, review the manuscripts, and make judgments on degrees of recommendations and levels of evidence. SBD Renal Disease Department drafted the manuscript selecting key clinical questions to make a narrative review using MEDLINE via PubMed, with the best evidence available including high-quality clinical trials, metanalysis, and large observational studies related to DKD diagnosis and treatment, by using the MeSH terms [diabetes], [type 2 diabetes], [type 1 diabetes] and [chronic kidney disease]. Results The extensive review of the literature made by the 14 members of the Central Committee defined 24 recommendations. Three levels of evidence were considered: A. Data from more than 1 randomized clinical trial or 1 metanalysis of randomized clinical trials with low heterogeneity (I2 < 40%). B. Data from metanalysis, including large observational studies, a single randomized clinical trial, or a pre-specified subgroup analysis. C: Data from small or non-randomized studies, exploratory analyses, or consensus of expert opinion. The degree of recommendation was obtained based on a poll sent to the panelists, using the following criteria: Grade I: when more than 90% of agreement; Grade IIa 75–89% of agreement; IIb 50–74% of agreement, and III, when most of the panelist recommends against a defined treatment. Conclusions To prevent or at least postpone the advanced stages of DKD with the associated cardiovascular complications, intensive glycemic and blood pressure control are required, as well as the use of renin–angiotensin–aldosterone system blocker agents such as ARB, ACEI, and MRA. Recently, SGLT2 inhibitors and GLP1 receptor agonists have been added to the therapeutic arsenal, with well-proven benefits regarding kidney protection and patients’ survival.
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