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The Effects Of NUCB2/Nesfatin-1 On Metabolism In Vivo

Posted on:2012-08-05Degree:DoctorType:Dissertation
Country:ChinaCandidate:W ZhuFull Text:PDF
GTID:1114330335487133Subject:Internal Medicine
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Objective To investigate the changes of plasma Nesfatin-1 and its relationship with HOMA-IR, body mass index (BMI), waist hip ratio (WHR), fasting plasma insulin levels (FINS) as well as other factors in patients with impaired glucose regulation (IGR) and Type 2 Diabetes (T2DM).Methods Plasma Nesfatin-1 assayed by ELISA were compared among IGR and T2DM, and control groups. The correlationship between plasma Nesfatin-1 and BMI, WHR, HOMA-IR, FINS were also analyzed.Results Plasma Nesfatin-1 in patients with IGR and T2DM were significantly elevated compared with controls ([1.91±0.79 and 1.80±0.80 vs. 1.41±0.58)μg/L, P<0.01]. Plasma Nesfatin-1 levels correlated positively with BMI,HbA1C,WHR,FBG,FINS and HOMA-IR(r=0.27, r=0.21, r=0.17, r=0.21, r=0.18, r=0.30, P<0.01和P<0.05).Multiple regression analysis showed that BMI and HOMA-IR were independent risk factors influencing plasma Nesfatin-1.Conclusion The changes of Nesfatin-1 levels are associated with glucose metabolism disorder and insulin resistance (IR), and it may contribute, at least in part, to the pathogenesis of IR and T2DM.Objective To evaluate the level of plasma Nesfatin-1 in patients who were metabolic syndrome positive and negative. And investigate the relationship between plasma Nesfatin-1 levels and HOMA-IR, body mass index (BMI), waist hip ratio (WHR), fasting plasma insulin levels (FINS), its diagnostic significance in metabolic syndrome was also explored.Methods 122 patients were recruited in this study. Patients were classified based on the CDS criteria (2004)of the metabolic syndrome. Plasma Nesfatin-1 levels were assayed by ELISA in 60 patients who were metabolic syndrome positive and 62 patients who were metabolic syndrome negative. We also investigate the relationship between plasma Nesfatin-1 levels and HOMA-IR, body mass index (BMI), waist hip ratio (WHR), fasting plasma insulin levels (FINS) and the diagnostic significance of it for metabolic syndrome.Results Plasma Nesfatin-1 levels in patients with metabolic syndrome positive were significantly elevated compared with controls. [(1.84±0.80 vs. 1.50±0.63)μg/L, P<0.01]. Plasma Nesfatin-1 levels correlated positively with BMI, WC, FBG, 2hPG, HbA1C, FINS and HOMA-IR. (r=0.30, r=0.24, r=0.24, r=0.31, r=0.23,r=0.30,r=0.37, P<0.05和P<0.01).Multiple regression analysis showed that BMI and HOMA-IR were independent risk factors influencing plasma Nesfatin-1 levels. Logistic regression analysis suggested the importance of FBG, BMI and insulin resistance in the diagnosis of metabolic syndrome.Conclusion As a factor of inhibiting food intake, Nesfatin-1 may played the important role in the pathogenesis of metabolic syndrome who had the insulin resistance. In the beginning, Nesfatin-1 may increased to suppress food by compensatory mechanisms and then decreased weight to improve the severe insulin resistance, delaying the development of disease. Objective To investigate the effects of high lever of Nesfatin-1 (1-82) recombinant proteins in ventricle on glucose-lipid metabolism in rats and the related enzymes.Methods Construct the system of micro infusion to the third ventricle, then according to the different liquids infused to the third ventricle, we divided rats into two groups, NN group is a group infused Nesfatin-1 (1-82) recombinant proteins, NC group is artificial cerebrospinal fluid infusion group,and the insulin sensitivity and glucose-lipid metabolism were assessed by the hyperinsulinemic- euglycemic clamp technique using 3-[3H] glucose as a tracer, the related enzymes were assessed by RT-PCR and detection of enzyme activity.Results During the steady-state of clamp, Glucose infusion rate(GIR) in NN group were significantly higher than in NC group (28.25±1.42 vs. 23.03±1.75 mg.kg-1.min-1,P<0.01). In the end of clamp, glucose disappearance rate (GRd) was significantly higher in NN group than that in NC group (34.92±1.38 vs. 31.84±1.84,P<0.01). The inhibition rate of hepatic glucose production was also significantly higher than NC group. (53 % vs. 37%, 6.67±0.33 vs. 8.81±2.93 mg.kg-1.min-1,P<0.01);The result of RT-PCR shows the PEPCK mRNA expression of liver tissues in NN group was significantly lower compared with NC group(10.67±0.95 vs. 21.04±0.34,P<0.01 ), and the activity of PEPCK in NN group also lower than NC group (10.7±0.9 vs. 21.0±0.3 mU/mg, P<0.01).Conclusion Intracerebroventricular infusion of small doses of Nesfatin-1 (1-82) recombinant protein can enhance insulin sensitivity of liver, which probably plays its physiological functions by inhibiting gluconeogenesis.
Keywords/Search Tags:Nesfatin-1, Insulin resistance, Impaired glucose regulation, Type 2 diabeics, metabolic syndrome, PEPCK, G-6-P, Glucose-lipid metabolism
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