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The Expression Of GLUT2and PTP-1B In The Pancreas Of Rats With Hyperthyroidism During Gestation Period

Posted on:2015-01-15Degree:MasterType:Thesis
Country:ChinaCandidate:Y R ZhangFull Text:PDF
GTID:2254330428974290Subject:Internal Medicine
Abstract/Summary:PDF Full Text Request
Objective: Hyperthyroidism is a syndrome of systemic hypermetabolismas the main performance,good hair at child-bearing age women, the incidencerate of0.2%-0.4%. Thyroid hormone is closely related to glucose metabolism.Due to placenta secretes hormones during pregnancy can also affect the norm-al also affect the normal glucose metabolism, pregnancy associated with hype-rthyroidism prone to disorders of glucose metabolism. GLUT2is a kind ofmembrane protein that mediates glucose uptake, is the main carrier of isletbeta cells to absorb glucose, play a key role on islet beta cells secrete insulin.Too much thyroid hormone can influence the expression of GLUT2in βcells.PTP–1B is a member of the family of protein tyrosine phosphatase, areexpressed in in multiple tissues and cells, which can increase thephosphorylation of insulin receptors and substrate, hinder the normal insulinsignaling cascade down, ultimately affect the transport of glucose in the bloodinto the cells and lead to hyperglycemia. Through the admeasurement ofGLUT2and PTP-1B expressed in pancreas in pregnancy withhyperthyroidism, further to research the possible mechanism of effect of β-cellfunction and glucose metabolis-m,and provide theoretical basis for earlyprevention and treatment of abnormal glucose metabolism.Methods: The female SD rats were randomly divided into non pregnancygroup and will be pregnant group, will be pregnant rats according to theproportion of male and female2:1into the cage. After conception they weredivided into single pregnancy group (group R), the pregnancy with the lowdose of levothyroxine sodium group (RA group), the pregnancy with themiddle dose of levothyroxine sodium group (group RB), the pregnancy withthe high dose of levothyroxine sodium group (group RC), non pregnant groupwere randomly divided into normal control group (group N), low dose of levothyroxine sodium group (group A), middle dose of levothyroxine sodium(group B), high dose group (group C).The rats in A group, B group,Cgroup,RAgroup, RBgroup, RCgroup were given different doses oflevothyroxine sodium, the rats in normal control group and simple pregnancygroup were given the same amount of saline. To observe the mothers’generalcharacter, detection rats in each group thyroid function, fasting plasma glucoseand fasting insulin. To measure the GLUT-2and PTP-1B expression contentin rats’ pancreas by the means of western blot technology.Results:1Non pregnant female rats were compared among groups:1.1The nonpregnant female rats’ general character: The nonpregnant femalerats’activity, diet quantity and water quantity in low dose of levothyroxinesodium group was slightly increased than normal control group, thestimulation reaction to the outside more sensitive and defecate numberincrease. The rats in middle dose group change significantly than low dosegroup;These changes are more obviously, irritability, hair wet in high dosegroup and bowel movements are thin paste, there was high metabolicsyndrome performance.1.2The nonpregnant female rats’ thyroid function: With the increase oflevothyroxine sodium dosage, FT3, FT4showed a trend of rising;TSH is onthe decline.The level of FT3and FT4of the low dose group,middle dosegroup and high dose group was more significantly increased than normalcontrol group(P<0.05). The level of TSH of the low dose group,middle dosegroup and high dose group was decreased significantly than normal controlgroup(P<0.05). And the level of FT3and FT4increased, TSH decreased inmiddle dose group than in lowe dose group (P<0.05), high dose group than inmiddle dose group FT3, FT4increased, TSH decreased (P<0.05).1.3The nonpregnant hyperthyroidism group rats’ pancreatic function: Fastingblood glucose in low,middle and high dose group rats significantly higher thannormal control group, and fasting blood glucose in high dose group ratshigher than middle dose group. Fasting insulin in high dose group were significantly higher than those in control group(P<0.05). Fasting insulin inlow and middle group is linear increased compared with normal control group,but no statistical difference. Insulin resistance index in middle and high dosegroup is obviously higher than in normal control group(P<0.05). And highdose group rats of insulin resistance index is higher than in the middle dosegroup (P<0.05), middle dose group rats of insulin resistance index is linearincreased compared with normal control group, but no statistical difference(P>0.05). Low, middle and high dose group rats’ islet β-cell function indexis significantly lower than normal control group (P<0.05), and high dosegroup rats’ islet β-cell function index is lower than in the middle dose group(P<0.05), middle dose group rats’ islet β-cell function index is relativelyreduced compared with low dose group of mice, but no statistical difference(P>0.05).2Comparison between the groups of pregnancy rats:2.1Each pregnant rats’general character: Simple pregnancy group rats withgestational development, gradually increasing body weight. Pregnancy withthe low dose of levothyroxine sodium group compared with pure pregnancygroup, weight increase slowly, and more sensitive to outside stimulation, moreirritable. And the pregnancy with the middle dose group weight increase moreslowly than the pregnancy with low dose group. The pregnancy with high dosegroup weight increase most slowly.2.2Each pregnant rats’ thyroid function: With the increase of levothyroxinesodium dosage, FT3, FT4showed a trend of rising;TSH is on the decline.Thelevel of FT3and FT4of the pregnancy with low dose of levothyroxine sodiumgroup,with middle dose group and with high dose group was moresignificantly increased than simple pregnancy group(P<0.05). The level ofTSH of the pregnancy with low dose group,with middle dose group and withhigh dose group was decreased significantly than simple pregnancy group(P<0.05). And the level of FT3and FT4increased, TSH decreased inpregnancy with middle dose group than with low dose group (P<0.05),pregnancy with high dose group than in group with middle dose FT3, FT4 increased, TSH decreased (P<0.05).2.3Pregnant group rats’pancreatic function: Fasting blood glucose inpregnancy with low,middle and high dose of levothyroxine sodium ratssignificantly higher than normal control group(P<0.05), and fasting bloodglucose in pregnancy with high dose rats higher than with middle dosegroup(P<0.05), and fasting blood glucose in pregnancy with middle dose ratshigher than with low dose group(P<0.05). Fasting insulin in pregnancy withhigh dose group were significantly higher than those in simple pregnancygroup(P<0.05). Insulin resistance index in pregnancy with low,middle andhigh dose group is obviously higher than in simple pregnancy group(P<0.05).And pregnancy with high dose group rats of insulin resistance index is higherthan with low dose group (P<0.05). Pregnancy with low, middle and highdose group rats’ islet β-cell function index is significantly lower than simplepregnancy group (P<0.05), and pregnancy with high dose group rats’ isletβ-cell function index is lower than in the low dose group (P<0.05),andpregnancy with middle dose group rats’ islet β-cell function index is lowerthan in the low dose group (P<0.05).3Pregnancy compared with the nonpregnant female groups:3.1Pregnancy compared with non pregnancy groups of the thyroid function:Pregnancy and non pregnancy groups were compared each group TSHdecreased (P<0.05), but no significant difference in FT3, FT4(P>0.05).3.2Pregnancy compared with non pregnancy groups of the pancreatic function:Pregnancy group compared with the female of nonpregnancy, the fastingblood glucose has no obvious difference (P>0.05), pregnancy group comparedwith the female of nonpregnancy,the fasting insulin increased (P<0.05), theβ-cell function is reduced, with statistical significance (P<0.05), the pregnancygroup rats than in those of nonpregnancy, insulin resistance index increase,with statistical significance (P<0.05).4The rats’pancreatic tissue’ GLUT-2protein expression quantity:4.1The rats’pancreatic tissue’ GLUT-2protein expression in nonpregnancy:Low,middle and high dose of levothyroxine sodium group rats’pancreatic tissue’ GLUT-2protein expression quantity was significantly lower than thatof normal control group,and middle dose group was decreased than low dosegroup,and high dose group was significantly decreased than middle dosegroup (P<0.05).4.2The rats’pancreatic tissue’ GLUT-2protein expression in pregnancy:Pregnancy with low,middle and high dose of levothyroxine sodiumrats’pancreatic tissue’ GLUT-2protein expression quantity was significantlylower than that of simple pregnancy group,and pregnancy with middle dosegroup was decreased than with low dose group,and pregnancy with high dosegroup was significantly decreased than with middle dose group (P<0.05).4.3The rats’pancreatic tissue’ GLUT-2protein expression quantity inpregnancy and nonpregnancy: Simple pregnancy group rats’ GLUT-2expression quantity compared with normal control group no statisticaldifference (P>0.05), pregnancy with low dose group GLUT-2was decreasedthan low dose group, pregnancy with middle dose group GLUT-2expressionwas decreased than middle dose group, pregnancy with high dose groupGLUT-2was decreased than high dose group (P<0.05).5The rats’pancreatic tissue’PTP-1B protein expression quantity:5.1The rats’pancreatic tissue’ GLUT-2protein expression in nonpregnancy:Low,middle and high dose of levothyroxine sodium group rats’pancreatictissue’ PTP-1B protein expression quantity was significantly higher than thatof normal control group,and middle dose group was increased than low dsoegroup,and high dose group was significantly increased than middle dose group(P<0.05).5.2The rats’pancreatic tissue’ PTP-1B protein expression in pregnancy:Pregnancy with low,middle and high dose of levothyroxine sodiumrats’pancreatic tissue’ PTP-1B protein expression quantity was significantlyhigher than that of simple pregnancy group,and pregnancy with middle dsoegroup was increased than with low dsoe group,and pregnancy with high dosegroup was significantly increased than with middle dose group (P<0.05).5.3The rats’pancreatic tissue’ PTP-1B protein expression quantity in pregnancy and nonpregnancy: Simple pregnancy group rats’ PTP-1Bexpression quantity compared with normal control group no statisticaldifference (P>0.05), pregnancy with low dose group PTP-1B was increasedthan low dose group, pregnancy with middle dose group PTP-1B expressionwas increased than middle dose group, pregnancy with high dose groupPTP-1B was increased than high dose group (P<0.05).Conclusion:1Pregnant rats can have insulin resistance, reduce islet beta cell function,to a certain extent affect glucose metabolism.2Female rats under different degree of hyperthyroidism can show thetendency of elevated blood glucose, insulin resistance and reduced islet β-cellfunction.3Mothers during pregnancy combined with hyperthyroidism mayincrease the damage of β-cell function, high blood sugar condition, it may beassociated with reduced GLUT-2protein expression.4Mothers during pregnancy combined with hyperthyroidism, increasedinsulin resistance, which may be related to effects of β-cell insulin signaltransduction pathway and increased the expression of PTP-1B.
Keywords/Search Tags:Hyperthyroidism, Pregnancy, Pancreas, Glucose transportprotein2, PTP-1B
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