Regulation of gluconeogenesis in liver, kidney and intestine by glucagon / 中国药理学通报

Aim To investigate the regulatory effect of glucagon on gluconeogenesis in liver, kidney and intes¬tine during different fasting periods and the underlying mechanism. Methods The 8-week-old male C57BIV 6J mice were randomly divided into six groups ( n = 6) :control group, control + glucagon group, fasting 18 h group, fasting 18 h + glucagon group, fasting 36 h group, and fasting 36 h + glucagon group. Glucose, triglyceride ( TG) and free fatty acids ( FFAs ) kits were used to detect their serum contents in mouse in-traperitoneal injection of glucagon at different fasting time points. Besides, liver/muscle glycogen assay kit and PAS staining were used to detect the glycogen con¬tents in liver tissue. RT-PCR method was used to observe the effects of glucagon on the gene expressions of peroxisome proliferators-activated receptor y coactivator la (PGC-1α), glucose-6-phosphatase (G6Pase) and phosphoenol pyruvate carboxykinase 1 (PEPCK) in liver, kidney and intestine of mice at different fasting time. Western blot was employed to detect the protein expressions of PGC-1α, G6Pase, PEPCK, phosphoryl-ase protein kinase A ( p-PKA) , protlein kinase A (PKA) , phosphorylase cAMp-response element binding protein (p-CREB) and cAMp-response element binding protein (CREB) in liver, kidney and intestine of mice were. Results (1) Glucagon increased the serum glucose level, reduced serum TG and FFAs levels, and reduced the hepatic glycogen content. (2) Glucagon promoted gluconeogenesis via upregulation of PGC-1α. On the stimulation of glucagon, PGC-1α gene and protein expressions in liver were significantly raised by glucagon when the mice were fasted 18 h and 36 h, while the gene and protein expressions of PGC-1α in kidney were obviously up-regulated by glucagon after fasting 18 h. However, PGC-1α gene and protein expressions in intestine were significantly elevated by glucagon at 36 h after fasting. (3 ) Glucagon induced gene and protein expressions of gluconeogenesis-related enzymes G6Pase and PEPCK in liver, kidney and intestine after fasting. (4 ) Glucagon upregulated p-PKA/PKA and p-CREB/CREB in liver. Conclusions Glucagon shows temporal difference in the gluconeo-genic response of liver, kidney and intestine in mice. Glucagon promotes the gene and protein expressions of key gluconeogenic enzymes G6Pase and PEPCK by increasing PGC-1α gene and protein expression, and thus increasing fasting blood glucose. Besides, glucagon promotes hepatic gluconeogenesis via PKA/CREB signaling pathway.

The gene knockout of ATlaR improves insulin resistance induced by high-fat diet in rats / 中国药理学通报

Aim To explore the role of angiotensin U type 1 a reeeptor ( AT 1 aR ) , an important component of HAS, in obesity-induced insulin resistance.Methods Wild type ( WT) and ATlaR gene knockout (ATlaR ) SD rats were fed with normal diet and 60% high-fat diet for 12 weeks, respectively.After 12 weeks, blood was collected from the abdominal aorta of rats to obtain serum, and the serum insulin level was measured by ELISA.The epididvmal adipose tissue was obtained, and gene expressions of peroxisome pro- liferator-activated receptor -y ( PPAR7) and sterol reg¬ulator}' element binding protein lc (SREBP-lc) in ad¬ipose tissue were detected by RT-PCR method.The protein expressions of insulin signaling pathway and protein kinase C (PKC) in adipose tissue were detec¬ted by Western blot.Results ATI aR knockout signif¬icantly reduced HOMA-IR and improved insulin resist¬ance induced by high-fat diet.In ATlaR rats fed with high-fat, the protein expressions of insulin signa¬ling pathway were much higher than those of WT rats, indicating that ATlaR gene knockout improved the in¬sulin signaling pathway in high-fat diet.In addition, the PKCa, PKCe and PKCr| expressions of ATlaR rats were significantly lower than those of WT rats.And the gene expressions of PPAR-y and SREBP-lc, which promoted adipogenic differentiation, significantly increased in ATlaR rats fed with a high-fat diet, demonstrating that ATlaR knockout promoted adipo¬genic differentiation.Conclusions ATlaR knockout significantly improves high-fat diet induced 1R by en¬hancing protein expressions of insulin signaling path¬way, inhibiting PKC expression and promoting adipo¬genic differentiation.

Local application of tranexamic acid reduces blood less in unilateral total knee arthroplasty: a retrospective comparison analysis / 中华外科杂志

<p><b>OBJECTIVE</b>To investigate the efficacy and safety of tranexamic acid in patients who receiving unilateral total knee arthroplasty (TKA).</p><p><b>METHODS</b>From March 2011 to March 2012, clinical data of 95 patients who received primary unilateral TKA were analyzed retrospectively, including 23 male and 72 female patients, age from 60 to 87 years, mean (71 ± 4) years. The patients in treatment group received 0.5 g of tranexamic acid inside knee joint after capsule closure, and patients in control group did not receive tranexamic acid. Two groups of patient's age, height, weight and disease diagnosis and other parameters of the differences were no statistical significance (P > 0.05). The amounts of intraoperative blood loss, postoperative visible blood loss, the hidden blood loss, and blood transfusion, the number of patients needing blood transfusion, symptoms of deep venous thrombosis and lower extremity ecchymosis were observed. The values of preoperative and 3 hours of postoperative D-dimer and related coagulation markers were recorded. Group t test was used to compare between the two groups.</p><p><b>RESULTS</b>There were no significant differences in intraoperative blood loss (P > 0.05). The amounts of postoperative visible blood loss, the hidden blood loss was significant different (t = 17.51 and 64.18, P < 0.05). Transfusion of both groups were (470 ± 150) ml and (708 ± 245) ml. The value of postoperative hemoglobin and hematocrit was lower in control group as compared with those in treatment group (t = -18.88 and -13.05, P < 0.05). No deep venous thrombosis was observed through Doppler ultrasound examination. Postoperative 3 hours D-dimer in the two groups for (0.91 ± 0.44) and (1.21 ± 0.65) mg/L, were significantly higher than that of preoperative (0.36 ± 0.11) and (0.37 ± 0.14) mg/L, with a statistically significant difference (t = 5.40 and 44.68, P < 0.05), and the control group was higher than treatment group (t = 1.99, P < 0.05). There was not statistically significant difference between the coagulation indicators of the two groups.</p><p><b>CONCLUSIONS</b>The local application of tranexamic acid intraoperatively in unilateral TKA patients could significantly reduce the amounts of postoperative blood loss and blood transfusion to avoid TKA patients' perioperative anemia-related complications. It is also safe, ecnomic and easy to use during surgery.</p>

Both the medial and lateral meniscal allograft transplantation following the anterior cruciate ligament reconstruction by arthroscopic surgical technique / 中华外科杂志

<p><b>OBJECTIVE</b>To discuss the minimal invasive arthroscopic surgery technique and clinical results of both the medial and lateral meniscal transplantation following the anterior cruciate ligament reconstruction with double bundles and bone tunnels.</p><p><b>METHODS</b>In August 2008 a minimal invasive surgery of both the medial and lateral meniscal allograft transplantation following anterior cruciate ligament reconstruction was preformed for 1 case with both the medial and lateral meniscectomy by arthroscopic surgery. The method of two bone plugs attached on tibial plateau was employed for medial meniscal allograft transplantation and the technique the bridge in slot for lateral meniscal allograft transplantation. The VAS, Lysholm score and IKDC rating were recorded before and after operation. The stability of knee was assessed by Lachman test, drawer sign and pivot shift test.</p><p><b>RESULTS</b>The patient was followed up 26 month after the operations. The degrees of knee flexion, extension and function of walk were normal. The Lachman test, drawer sign and pivot shift test were nearly normal. The VAS after operation was 2 points lower than that before operation. The Lysholm score post-operation was 20 points higher than pre-operation. The IKDC became B degree in late following-up from C degree before the operation. MRI revealed anterior cruciate ligament graft was continuous and the meniscal allograft was normal shape on year 1 after the operation. The posterior horn of medial meniscal allograft and anterior corner of lateral meniscal allograft showed slightly shrunk. The second-look arthroscopy showed that the healing occurring between meniscal allograft and the capsule and meniscal allograft was normal shape on month 18 after the operation. The anterior horn of medial and lateral meniscus was slightly worn.</p><p><b>CONCLUSIONS</b>Both the medial and lateral meniscal transplantation following the anterior cruciate ligament reconstruction in appropriately selected patients with the medial and lateral meniscus-deficient knee may recover the knee mechanic balance and stability, which is a option of treatment for that young and activity patients. It is proposed that the medial and lateral meniscal grafts harvested from a single donator. Attention should be paid to the direction of the bone tunnels fixing the horns of the meniscus in order to avoid communication with the tunnels of anterior cruciate ligament reconstruction.</p>