Effect of metformin on insulin resistance during catch-up growth in mice with fetal growth restriction / 南方医科大学学报

<p><b>OBJECTIVE</b>To study the efficacy of metformin intervention on insulin resistance during catch-up growth in mice with fetal growth restriction (FGR).</p><p><b>METHODS</b>Mouse models of FGR were established by low protein diet feeding of the pregnant mice. Both the newborn female mice with FGR and normal control (NC) mice were randomized for feeding with a standard diet (SF) or a high-fat diet (HF) after weaning and treatment with gavage of either metformin or normal saline. The mice were examined for vaginal opening time and the estrous cycle at the age of 8 weeks. At the age of 12 weeks, 6 mice in anestrus from each group were fasted for 12 h for measurement of body weight, height, poundera index (PI), fasting blood glucose (FBG), fasting insulin (Fins), follicle stimulating hormone (FSH) and anti-Mullerian hormone (AMH), and the HOMA-IR was calculated. The reproductive capacity of female mice was assessed by mixing them with male mice at the ratio of 2:1. The 3 × 2 factorial analysis was conducted to determine the interactions between FGR, high-fat feeding and metformin.</p><p><b>RESULTS</b>Factorial analysis showed that FGR and high-fat feeding had significant effects on the PI index, Fins, HOMA-IR, vaginal opening time, and AMH (P<0.05). Metformin significantly affected the factors related to high-fat feeding including weight, PI, FPG, Fins, HOMA-IR and estrous cycle (P<0.05) and the factors related to FGR with the exception of height and FSH (P<0.05). FGR significantly affected the factors tested except for body weight (P<0.05); high-fat feeding affected all the factors but the FSH (P<0.05); metformin affected all the factors but the height and FSH (P<0.05). In the female mice treated with saline, the pregnancy rates differed significantly between FGR mice with high-fat feeding and control mice with standard feeding, and between FGR mice with standard feeding and high-fat feeding (P<0.05).</p><p><b>CONCLUSION</b>FGR mice can present with delayed puberty with rare ovulation and adulthood insulin resistance, and high-fat feeding after birth can promote the catch-up growth of FGR mice. Metformin intervention is effective for improving insulin resistance and reproductive-endocrine disorders in FGR mice during catch-up growth.</p>

Insulin resistance and carotid atherosclerosis in 221 patients with potential hyperglycemia / 中国医学科学杂志(英文版)

<p><b>OBJECTIVE</b>To investigate the relationship between insulin resistance and carotid atherosclerosis in patients with potential hyperglycemia.</p><p><b>METHODS</b>A total of 221 patients were recruited among those with potential hyperglycemia. All participants underwent physical examination, medical history interview, and 75 g oral glucose tolerance test. Venous blood was sampled for measurement of insulin and cholesterol levels. The intima-media thickness (IMT) in bilateral common carotid arteries was observed by B-mode ultrasound. Insulin resistance index was calculated by homeostasis model assessment (HOMA-IR). Subjects were stratified in quintiles according to HOMA-IR values. Risk factors and atherosclerotic parameters were analyzed.</p><p><b>RESULTS</b>With HOMA-IR value increase, incidence of impaired glucose tolerance, diabetes mellitus, hypertension, and coronary artery disease increased, the levels of triglyceride (TG), low density lipoprotein cholesterol (LDL-C), fasting plasma glucose, 2 hour plasma glucose, and fasting insulin increased as well, while the level of high density lipoprotein cholesterol (HDL-C) decreased. Meanwhile, all atherosclerotic parameters increased. Multivariate regression analysis showed that TG, total cholesterol, HDL-C, LDL-C levels, and ln(HOMA-IR) were related to IMT, hence were risk factors for IMT increase.</p><p><b>CONCLUSION</b>Insulin resistance is implicated in atherogenesis.</p>

Proliferative response of human prostate cancer cell to hormone inhibited by androgen receptor antisense RNA / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The failure of endocrine treatment for advanced prostate cancer might be related to aberrant activation of androgen receptor (AR). Prostate cancer cell line LNCaP contains AR that can be activated by androgen, estrogen and progesterone. This study was set to investigate the effects of antisense AR RNA on growth of LNCaP cultured in medium containing varied concentrations of R1881, 17beta-estradiol, and progesterone, respectively.</p><p><b>METHODS</b>LNCaP cells transfected with antisense AR RNA retroviral vector pL-AR-SN were designated as LNCaPas-AR. LNCaP cells containing empty vector pLXSN served as LNCaPNeo. LNCaP and LNCaPNeo were taken as controls. In vitro cell growth assay, proliferative cells of LNCaP and tranfected LNCaPs were counted by typan staining when they cultured with synthetic androgen R1881, 17beta-estradiol, and progesterone, respectively.</p><p><b>RESULTS</b>Growth of LNCaPas-AR was inhibited significantly (P < 0.05) compared with that of LNCaP and LNCaPNeo at 1 nmol/L R1881, 10 nmol/L 17beta-estradiol, and 1 nmol/L progesterone, respectively. No difference was seen between LNCaP and LNCaPNeo (P > 0.05). Microscopic observation showed that LNCaP and LNCaPNeo cells grew well, but only few LNCaPas-AR cells were alive.</p><p><b>CONCLUSIONS</b>Our observations indicate that antisense AR RNA retroviral vector pL-AR-SN could change androgen-independent characteristics of LNCaP cells, which might shed some novel insights into the treatment of androgen-independent prostate cancer.</p>

Investigation of the carotid intima-media thickness in 221 individuals with metabolic syndrome / 中华内分泌代谢杂志

Metabolic abnormalities were identified and carotid intima-media-thickness(IMT)was measured in 221 individuals at risk for metabolic syndrome(MS).The results indicated that IMT was significantly thicker in MS individuals than that in non-MS individuals(P＜0.01).And there was a tendency of progressive increase in IMT with increasing components of metabolic syndrome.