Effects of ghrelin on mice of obesity and insulin resistance / 医学研究生学报

ObjectiveThe effect of ghrelin on glucose metabolism is still controversial. This study aims to investigate the effects of long-term application of acyl ghrelin (AG) and des-acyl ghrelin (DAG) on insulin resistance and serum inflammatory factor levels by establishing a mouse model of obesity, induced by a high-fat diet.MethodsThirty two male C57BL/6 mice were randomly divided into 4 groups, 8 in each group. Except for the control group, the high fat diet group (HFD), HFD+AG group and HFD+DAG group were given a high-fat diet to induce obesity in mice. Control group: standard feed and an intraperitoneal injection of 10mL isotonic saline were given every day. HFD: high-fat feed and an intraperitoneal injection of 10mL isotonic saline were given every day. HFD+AG group: high-fat diet was fed with 0.8mg AG; HFD+DAG group: high-fat diet was fed with 0.8mg DAG. Intraperitoneal glucose tolerance test (IPGTT) was performed 16 weeks later. The blood glucose was collected from the tail veins at 0min, 30min, 60min and 120min after injection, respectively, the fluctuation curve was drawn, the area under the curve was calculated, and then the epididymal fat index was weighted. Fasting insulin, interleukin 6 (IL6) and TNFα levels were measured by enzyme-linked immunosorbent assay (ELISA). Then the insulin resistance index (HOMA IR) was compared.ResultsAfter 6 weeks of feeding, the weight of the mice in HFD was significantly higher than that of the control group (P<0.05). After 14 and 12 weeks of administration, the mice in the HFD+AG group and the HFD+DAG group had a significant weight loss (P<0.05). The fat mass of the epididymis in the HFD+DAG group [(0.92±0.32)g] was significantly lower than that of the HFD group [(1.08±0.11)g] (P<0.05); the fasting insulin level was significantly lower, too (P<0.05). The insulin resistance index (4.94±1.27, 4.08±1.35), IL6 [(34.82±6.23), (36.90±5.27)pg/mL] and TNFα levels [(73.01±7.75), (69.39±8.43)pg/mL] in the HFD+AG group and HFD+DAG group were significantly lower than those in the HFD group [(81.70±7.53), (45.85±6.41) pg/mL, (81.70±7.53)pg/mL], with statistically significant differences (P<0.05). The serum levels of IL 6 and TNFα in the HFD group were significantly lower than those in the control group (P<0.05).ConclusionLong-term application of AG and DAG could improve the insulin resistance and reduce the inflammation level of the mice induced by a high-fat diet. DAG can also decrease the visceral fat in mice.

Recent studies on the correlation of vitamin B12 and diabetes / 医学研究生学报

Vitamin B12 (VitB12) is one of the essential vitamins in humans and is involved in DNA synthesis and cellular metabolism. Many studies have shown that the lack of VitB12 is closely related to the occurrence and development of diabetes and its complications. Therefore, regular testing and reasonable supplementation of VitB12 can help prevent diabetes complications. The article reviews the relationship between VitB12 and diabetes as well as the application of VitB12 in diabetic patients.

Effects of rhein on insulin signaling pathway and its negative regulatory protein protein tyrosine phosphatase 1B / 医学研究生学报

Objective Recent studies have shown that rhein could improve glucose metabolism,while the specific mechanism is not yet clear，the aim of this study is to explore the effects of rhein on the insulin signaling pathway in C2C12 cells.Methods To measure the optimum substrate and optimum enzyme concentrations of rhein and the protein tyrosine phosphatase-1B(PTP1B)and calculate the half maximal inhibitory concentration of rhein on PTP1B(IC50). Differentiated and maturated C2C12 myotubes were divided into two groups, the rhein group and the control group. The rhein groups were treated with different rhein concentrations(0.1,1, 10,100 μmol/L) , the positive control group was given 10 nmol/L insulin stimulation for 0.5 hours and the blank control group was treated with equal volume solvent. Related proteins in the insulin signaling pathway were detected by Western blotting and PTP-1B activity was measured by immunoprecipitation.Results The IC50 of rhein to PTP1B was 80.5 μmol/L,and when C2C12 myotubes were treated with 100 μmol/L rhein, the activity of PTP1B decreased significantly. Compared with the blank control group, the rhein groups' phosphorylation levels in insulin receptor and insulin receptor substrates were enhanced and the levels of GLUT4 were obviously improved in C2C12 cells. Moreover, the protein levels of insulin receptor and insulin receptor substrates were not affected significantly.Conclusion Rhein could reduce the activity of PTP1B and enhance insulin signaling transduction. Therefore，we speculated that the enhancement of insulin signaling may be related to the decrease of PTP1B activity in skeletal muscle cells.

Effect of Schisandra chinensis on interleukins, glucose metabolism, and pituitary-adrenal and gonadal axis in rats under strenuous swimming exercise / 中国结合医学杂志

<p><b>OBJECTIVE</b>To investigate the effect of Chinese medicine (CM) Schisandra chinensis on interleukin (IL), glucose metabolism, and pituitary-adrenal and gonadal axis of rats after strenuous navigation and exercise.</p><p><b>METHODS</b>A total of 45 Sprague-Dawley rats were randomized into the quiet control group, the stress group, and the CM group (15 in each group). The CM group received 2.5 g/kg of Schisandra chinensis twice per day for one week before modeling. Except the quiet controls, rats were trained using the Bedford mode for 10 days. On the 11th day, they performed 3 h of stressful experimental navigation and 3 h of strenuous treadmill exercise. The levels of serum testosterone (T), cortisol (CORT), luteinizing hormone (LH), IL-1, IL-2, and IL-6 were tested by radioimmunoassay and enzyme-linked immunosorbent assay, respectively. The adrenal cortex ultrastructure was observed using electron microscopy.</p><p><b>RESULTS</b>Compared with the quiet control group, after navigation and strenuous exercise, blood glucose was increased, and T level was decreased in the stress group (both P<0.01). The blood glucose, CORT, IL-1 and IL-2 levels were significantly reduced in the CM group (P<0.05 or P<0.01) as compared with the stress group. Electron microscopy revealed that the rats in the CM group had a smaller decrease in adrenal intracellular lipid droplets and higher levels of apoptosis than those in the stress group.</p><p><b>CONCLUSIONS</b>Schisandra chinensis can reduce serum CORT and blood glucose levels in stressed rats. It appears to protect the cell structure of the adrenal cortex, and offset the negative effects of psychological stress and strenuous exercise related to immune dysfunction. Schisandra chinensis plays a regulatory role in immune function, and can decrease the influence of stress in rats.</p>

Effect of early intervention with rhein on islet function in db/db mice / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the hypoglycemic action of rhein (4,5-dihydroxyanthraquinone-2-carboxylic acid), one of the anthraquinone derivatives isolated from rhubarb, and study its effects on pancreatic beta-cells in db/db mice.</p><p><b>METHODS</b>Thirty 4-week-old db/db mice were randomized for an 8-week treatment with intragastric administration of rhein (120 mg/kg, n=15) or placebo (1% natrium cellulose solution, n=15). After the treatment, intraperitoneal glucose tolerance test (IPGTT) was performed and the area under curve (AUC) of insulin levels in IPGTT was calculated to evaluate insulin secretory function. The AUC(INS0-30) was calculated to evaluate the early-phase insulin secretion. Immunohistochemical staining for insulin was performed to estimate the beta-cell mass, and beta-cell apoptosis was detected using TUNEL assay.</p><p><b>RESULTS</b>Compared with the control group, rhein-treated group showed significantly reduced blood glucose concentrations at 0, 30, 60 and 120 min after glucose load with significantly higher insulin levels at 30, 60 and 120 min. The early-phase insulin secretion was also obviously increased. The beta-cell mass was obviously rescued by the 8-week treatment with rhein, which also notably improved the staining intensity of insulin and suppressed beta-cell apoptosis compared with the control.</p><p><b>CONCLUSIONS</b>Early rhein treatment significantly improves glucose tolerance by restoring the early-phase insulin secretion in db/db mice and inhibiting the apoptosis of the beta-cells, suggesting the potential of rhein as a novel therapeutic agent for type 2 diabetes.</p>

Effects of atorfastatin on the cognitive function of patients with vascular cognitive impairment and different apolipoprotein E genotypes / 南方医科大学学报

<p><b>OBJECTIVE</b>To study the effect of atorfastatin on the cognitive function of patients with vascular cognitive impairment (VCI) and different apolipoprotein E genotypes.</p><p><b>METHODS</b>The ApoE polymorphism was genotyped by PCR sequencing and the patients were divided into Eepsilon4 carrier (epsilon4+) group (n=24) and epsilon4- group (n=51). All the patients were given 20 mg oral atorfastatin every evening. The indices of TC, TG, HDL-C, LDL-C, as well as the scores of MMSE and clock-drawing test were compared between the two groups before and 24 weeks after the treatment.</p><p><b>RESULTS</b>Compared with those without epsilon4 allele, epsilon4+ patients had obviously increased plasma LDL level and lowered scores of MMSE. Plasma TC, TG and LDL-C were decreased significantly in the two groups after the treatment, and the improvement of TC was greater in patients without epsilon4 allele. The scores of MMSE increased significantly in patients with epsilon4 allele. The improvement in the scores of MMSE and clock-drawing test was greater in epsilon4+ group than in epsilon4- group.</p><p><b>CONCLUSION</b>Atorfastatin may improve the cognitive function in patients with VCI carrying epsilon4 allele, the effect of which may not be related to lowed blood lipids.</p>

Effects of schisandra on the function of the pituitary-adrenal cortex, gonadal axis and carbohydrate metabolism in rats undergoing experimental chronic psychological stress, navigation and strenuous exercise / 中华男科学杂志

<p><b>OBJECTIVE</b>To investigate the effects of schisandra on the function of the pituitary-adrenal cortex, gonadal axis and carbohydrate metabolism in male rats undergoing experimental chronic psychological stress, navigation and strenuous exercise.</p><p><b>METHODS</b>Thirty-four SD rats were randomly allocated into a non-stress group (Group A), a stress control group (Group B) and a schisandra group (Group C). The latter two groups received 10 days of Benford's high-intensity training, followed by 3 hours of wearing floating with psychological stress and another 3 hours of running at the speed of 26.7 m/min. Then blood samples were immediately obtained for the measurement of the levels of testosterone (T), corticosterone (CORT), luteinizing hormone (LH) and blood glucose (Glu). Meanwhile the adrenal gland was excised and its cortex ultrastructure observed under the electron microscope.</p><p><b>RESULTS</b>The Glu level was increased while the T level decreased significantly in Group B as compared with Group A. The CORT level remained unchanged in Group B. Both the Glu and CORT levels were significantly reduced in Group C in comparison with B. However, no significant differences were found in serum LH levels among the three groups. And electron microscopy revealed a reduction of lipid droplets and apoptosis of the adrenal cortex cells in Group B as compared with C.</p><p><b>CONCLUSION</b>Schisandra can reduce the levels of CORT and Glu and protect the structure of the adrenal cortex.</p>

Salidroside protects the hypothalamic-pituitary-gonad axis of male rats undergoing negative psychological stress in experimental navigation and intensive exercise / 中华男科学杂志

<p><b>OBJECTIVE</b>To study the effects of salidroside on the function and ultramicro-pathological change of the hypothalamic-pituitary-gonadal (HPG) axis of male rats in experimental navigation and intensive exercise.</p><p><b>METHODS</b>Six-week SD rats were randomized into 3 groups: non-stress control (NC, n = 10), training control (TC, n = 12) and salidroside treatment (ST, n = 12) group. Blood samples were collected from the NC rats that did not receive any stimulus after a 7-day intragastric administration of saline. The TC rats underwent a 10-day running training with increasing load on the treadmill followed by a 7-day intragastric administration of saline. The ST rats were subjected to the same process of running training as the TC group and received intragastric administration of salidroside. Then blood samples were immediately obtained and the levels of testosterone (T), corticosterone (CORT), adrenocorticotropic hormone (ACTH), luteinizing hormone (LH) and gonadotropin-releasing hormone (GnRH) measured by radioimmunoassay. The testis histopathology was observed by HE staining, and the ultrastructural changes of the pituitaries and testes investigated by electron microscopy.</p><p><b>RESULTS</b>The serum T level was significantly lower in the TC than in the NC group, but showed no significant difference between the ST and NC groups. HE staining revealed no significant difference in testis histopathology among the 3 groups. Ultramicro-pathology showed that the secretory granules of the pituitary cells were significantly reduced in the TC rats compared with the NC ones; the number of the granules significantly increased in the ST group compared with the TC rats; and mitochondrial swelling, increase of electron density and decrease/disappearance of mitochondrial cristae were observed in the Leydig cells of the TC rats. But no significant differences were found in the testicular cells between the ST and NC groups.</p><p><b>CONCLUSION</b>Negative psychological stress and intensive exercise can significantly suppress the function of the HPG axis in rats. Salidroside therapy has protective effect on the HPG axis.</p>

Experimental navigation and deuteroexhaustive exercise suppress the function of the hypothalamic-pituitary-testicle axis in rats / 中华男科学杂志

<p><b>OBJECTIVE</b>To study the effects of experimental navigation and deuteroexhaustive exercise on the serum levels of testosterone (T), corticosterone (CORT), luteinizing hormone (LH) and follicle stimulating hormone (FSH).</p><p><b>METHODS</b>Thirty-six male SD rats were randomly divided into an experimental navigation group (Group A), which underwent 180 min wearing floating with psychological stress, a deuteroexhaustive exercise group (Group B), which were subjected to 120 min intensive running on the treadmill after the accomplishment of the same procedure as Group A, and a control group (Group C). Blood samples were obtained at the end of the experiment to determine the T, CORT, LH and FSH of the rats.</p><p><b>RESULTS</b>Compared with Group C, serum T was statistically decreased in Group A and B (P < 0.05), while CORT was increased slightly in Group A and significantly in Group B (P < 0.05). A statistically lower level of serum LH was observed in Group B (P < 0.05), but no significant differences were found in serum FSH among the three groups.</p><p><b>CONCLUSION</b>Stresses of experimental navigation and intensive exercise suppress the function of the hypothalamic-pituitary-testicle axis in rats.</p>

Protection of candesartan on?-cell function and morphology in db/db mice / 中华内分泌代谢杂志

Objective To investigate whether and how candesartan treatment can attenuate the deleterious influence of hyperglycemia in diabetic(db/db) mice.Methods Eight-week-old db/db mice were randomized into candesartan eilexetil (1 mg/kg) or placebo group via gavage for 6 weeks.Their age-matched nondiabetie littermates db/m mice were treated with placebo and acted as non-diabetic control group.After 6 weeks' treatment, intraperitoneal glucose tolerance test,immunohistochemical stainings of oxidative stress markers [8-(OH) dG,4- HNE,NADPH oxidase],insulin,CD31,Azan staining and electron microscopy observation of islet?-cells were perfermed.Results As compared with placebo group,the improvement in glucose tolerance and marked saving of islet?-cell mass with candesartan for 6 weeks were noted.There were also notably decreased staining intensity in oxidative stress markers,such as 8-(OH) dG,4-HNE,p22~(phox),gp91~(phox),as well as attenuated intra-islet Azan staining and enhanced endothelium marker CD31 staining in islet.Under electron microscope,candesartan-treated mice showed significantly increased granulation of insulin and ameliorated proliferations of endoplasmic reticulum and Golgi bodies.Furthermore,swelling of mitochondria was relieved to nearly normal.Conclusion After diabetic onset,candesartan treatment does not reverse the state of diabetes but may effectively improve glucose tolerance and protect?-cell function by attenuating oxidative stress,islet fibrosis,sparsity of blood supply and uhrastructure disruption,and thus delays the?-cell failure.