Growth hormone improves insulin resistance in visceral adipose tissue after duodenal-jejunal bypass by regulating adiponectin secretion
Zi-Tian LiuGuangwei YangXiang ZhaoShuohui DongYang JiaoZheng GeAo YuXi-Qiang ZhangXin-Zhen XuZhiqiang ChengXiang ZhangKexin Wang
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BACKGROUND The mechanism of improvement of type 2 diabetes after duodenal-jejunal bypass (DJB) surgery is not clear. AIM To study the morphological and functional changes in adipose tissue after DJB and explore the potential mechanisms contributing to postoperative insulin sensitivity improvement of adipose tissue in a diabetic male rat model. METHODS DJB and sham surgery was performed in a-high-fat-diet/streptozotocin-induced diabetic rat model. All adipose tissue was weighed and observed under microscope. Use inguinal fat to represent subcutaneous adipose tissue (SAT) and mesangial fat to represent visceral adipose tissue. RNA-sequencing was utilized to evaluate gene expression alterations adipocytes. The hematoxylin and eosin staining, reverse transcription-quantitative polymerase chain reaction, western blot, and enzyme-linked immunosorbent assay were used to study the changes. Insulin resistance was evaluated by immunofluorescence. RESULTS After DJB, whole body blood glucose metabolism and insulin sensitivity in adipose tissue improved. Fat cell volume in both visceral adipose tissue (VAT) and SAT increased. Compared to SAT, VAT showed more significantly functional alterations after DJB and KEGG analysis indicated growth hormone (GH) pathway and downstream adiponectin secretion were involved in metabolic regulation. The circulating GH and adiponectin levels and GH receptor and adiponectin levels in VAT increased. Cytological experiment showed that GH stimulated adiponectin secretion and improve insulin sensitivity. CONCLUSION GH improves insulin resistance in VAT in male diabetic rats after receiving DJB, possibly by increasing adiponectin secretion.This chapter contains sections titled: Introduction Adiponectin Structure and Post-Translational Modifications Significance and Bioactivity of Adiponectin Multimers Adiponectin and Liver Adiponectin and Skeletal Muscle Adiponectin and the Vasculature Adiponectin and the Brain Adiponectin Expression and Secretion Adiponectin Secretion Ectopic Adiponectin Expression Regulation of Expression and Secretion Adiponectin Clearance Adiponectin Receptors and Downstream Effectors Adiponectin Signaling Conclusions References
Adiponectin receptor 1
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To identify the proportion of low adiponectin level and to evaluate the role of low adiponectin level, age, body mass index, and waist circumference on the occurrence of metabolic syndrome in women with insulin resistance.The study was done by a cross-sectional survey on adult women aged 30-60 years. The study was conducted at Fatmawati Hospital-Jakarta from January to March 2008 with a total sample of 33. The sample was selected consecutively based on the presence of metabolic syndrome according to the IDF 2005 criteria. The examination of plasma adiponectin level was done by ELISA method. Insulin resistance was defined if HOMA IR > or = 2 (calculated by fasting insulin (microU/mL) x Fasting blood sugar (mmol/L) divided by 22.5). Association of low adiponectin level with insulin resistance was evaluated by calculating the Odds Ratio.Seventeen of 33 subjects with metabolic syndrome have insulin resistance, in which 7 of them (41.18%) show low adiponectin level. While in 16 subjects without insulin resistance, only one subject (6.25%) has low adiponectin level. From 8 subjects with low adiponectin level, 7 of them (87.5%) have insulin resistance. In other words, low adiponectin level is associated with increased risk of insulin resistance (Odds Ratio 10.5, P = 0.040 (CI 95% : 1.12-98.91).Low adiponectin concentration increases the risk of developing insulin resistance much more than normal adiponectin level.
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Abstract Aims: To study circulating levels and distribution of adiponectin multimers [low molecular weight (LMW)-, medium molecular weight (MMW)- and high molecular weight (HMW)-adiponectin] in preterm and full-term infants. Methods: Total serum adiponectin and its multimers were measured in 40 healthy infants at the age of one month and associations with anthropometric parameters [body weight and length, body mass index (BMI)], weight gain and metabolic indices (glucose, insulin) were examined. Twenty of the infants were born preterm (gestational age 33.2±1.6 weeks). Results: LMW-adiponectin level and its fractional ratio to total adiponectin were significantly higher in full-term than in preterm infants (P<0.001 and P<0.01, respectively), whereas, MMW-adiponectin level and its ratio were significantly lower (P=0.03 and P=0.01, respectively). HMW-adiponectin did not differ significantly between full-term and preterm infants and accounted for almost 60% of total adiponectin levels in both groups. HMW-adiponectin, but not MMW adiponectin or LMW adiponectin, correlated significantly with anthropometric measurements, similarly to total adiponectin; in addition, HMW adiponectin correlated significantly with weight gain. Conclusions: HMW adiponectin is the most prevalent form in infants. Circulating levels and distribution of MMW- and LMW-adiponectin differ between full-term and preterm infants, but the role of these adiponectin multimers needs to be studied further.
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ObjectiveTo investigate the effect of intrauterine environment on adiponectin level in cord blood through comparison of normal pregnancy group and gestational diabetes group. MethodsThis cross sectional study included women with: normal pregnancy (n = 204); and patients with gestational diabetes mellitus (GDM) (n = 204).Among GDM patients, 118 were managed with diet alone and 86 were insulin requiring.Cord serum adiponectin concentration at birth was measured by enzyme-linked immunosorbent assay. ResultsCord serum adiponectin concentration was higher in GDM treatment pregnancies compared with normal pregnancies (P = 0.02).Cord serum adiponectin concentration was higher in female compared with male fetuses both normal and gestational diabetes pregnancies (P = 0.04, P = 0.03).In normal pregnancies, cord serum adiponectin concentration was positively correlated with gestational age (r = 0.2374, P < 0.02).In normal pregnancies, cord serum adiponectin concentration did not correlated with birth weight (r = -0.05,P > 0.05).Cord serum adiponectin concentration was not different between only diet treated women and insulin requiring women in GDM (P > 0.05). ConclusionSex dimorphism for adiponectin and the change of adiponectin in GDM offsprings, fi rst appear in utero.Higher adiponectin levels in females or GDM offsprings refl ect increased adiposity of the fetuses.
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Introduction: Adiponectin has been known to play an important role in the glucose and lipid metabolism, and thereby may be considered as a potential treatment target for diabetes mellitus or atherosclerotic diseases. Recently, some basic studies showed that adiponectin might not function in an insulin-resistant condition, a concept called “adiponectin resistance.” However, this concept has not been confirmed in human. Therefore, we assessed the hypothesis that the well-known inverse association between adiponectin and insulin resistance is weakened in the insulin-resistant state. Methods: We studied 2,316 middle-aged Japanese men without a medical history of cancer, cardiovascular disease, diabetes, hypertension, or dyslipidemia to determine whether or not the association between serum adiponectin levels and the insulin resistance index (HOMA-IR) differed according to insulin resistant states. Results: Mean age and body mass index of study subjects were 48±7 and 23±3, respectively. A multiple linear regression analysis revealed that log-adiponectin was inversely associated with log-HOMA-IR independently of covariates (β= − 0.235, P <0.001). Subsequently, we re-analyzed after dividing study subjects according to the tertile of HOMA-IR. As shown in the Table , the inverse association between adiponectin and HOMA-IR was considerably weakened with the escalation of insulin resistance. Specifically, adiponectin was almost positively associated with HOMA-IR in insulin-resistant subjects (β= 0.114, P =0.059). Interestingly, statistically significant associations of adiponectin with triglyceride and HDL-C were uniformly observed in all tertiles. Conclusion: The inverse association of adiponectin with insulin resistance weakened with the escalation of insulin resistance, suggesting the existence of “adiponectin resistance” in insulin-resistant individuals. This adiponectin resistance may be restricted in glucose metabolism. Table. Coefficients of adiponectin in multiple linear regression analyses with independent variables
Dyslipidemia
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Objective To explore the relationships between Serum levels of tumor necrosis factor-alpha TNFα,1L-6,adiponectin and insulin resistance in type 2 diabetes.Methods 80 T2DM patients and 40 healthy controls were recruited.Levels of serum TNF-α,IL-6,adiponectin,plasma glucose,insulin and BMI were measured.Insulin resistance was evaluated by HOMA-IR.Results The levels of TNF-α and IL-6 in T2DM group were significantly higher than that in control group(all P<0.05);The levels of adiponeetin in T2DM group was significantly lower than that in control group(P<0.05).The levels of TNF-α and IL-6 were positively correlated with HOMA-IR(P<0.05),adiponeetin was egatively correlated nwith HOMA-IR(P<0.01).Conclusion TNF-α,IL-6 and adiponectin were closely related with insulin resistance,and should take parts in development of T2DM.
Key words:
Diabetes mellitus,type 2; Insulin resistance; Cytokines; Adiponectin
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To assess insulin resistance and adiponectin profile in patients with chronic hepatitis C (CHC), according to the presence or absence of metabolic syndrome (MS).One hundred and fifty-two patients with histologically proven CHC, genotype I were prospectively studied. Parameters of MS according to the IDF criteria were evaluated. Insulin resistance was established by homeostasis model assessment (HOMA-IR]. An index > or = 2.0 was designated as IR and > or = 4 as prediabetic state. Serum adiponectin levels were measured by ELISA:MS was found in 61.48% of cases. HOMA-IR was significantly higher in patients with CHC and MS vs those without MS (7.88 +/- 1.11 vs 4.29 +/- 0.5, p=0.023]. Adiponectin levels had an inverse behaviour (9,946.1 +/- 5,811 ng/ml vs 13,215.5 +/- 815.5 ng/ml, p< 0.001]. By multiple linear regression analysis the independent predictors associated with HOMA-IR > or = 4 in patients with CHC and MS were visceral obesity, adiponectin levels, activity and degree of steatosis. Only visceral obesity and HOMA-IR were independently associated with adiponectin. A significant negative correlation was established between adiponectin and insulin (r = -0.169, p=0.003] and between adiponectin and HOMA-IR (r = -0.188, p=0.02].CHC with MS was associated with a higher insulin resistance and lower adiponectin level. Adiponectin level and insulin resistance were significantly correlated.
Steatosis
Homeostatic model assessment
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Adiponectin is one of the novel adipocytokines participates in the development of insulin resistance which is the common pathological basis of Type 2 Diabetes Mellitus and Metabolic Syndrome.Numerous studies have demonstrated that adiponectin is significantly correlated with the development of insulin resistance.It can ameliorate insulin sensitivity,improves glucose and lipid metabolism in vivo.The levels of adiponectin in vivo could predict the development of insulin resistance.Simultaneously,various of methods could ameliorate insulin resistance by increasing the levels of adiponectin in vivo in Traditional Chinese Medicine.Discovery of adiponectin provides a new idea for the theoretical studies and clinical preventions to insulin resistance.
Carbohydrate Metabolism
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Objective To investigate serum adiponectin levels in metabolic syndrome patients without diabetes and to analyse the relationship between serum adiponectin levels,and Insulin resistance(IR).Methods 92 metabolic syndrome patients without diabetes and 30 health persons were investigated. Serum adiponectin levels of all subjects were determined by using enzyme linked immunosorbent assay(ELISA).Homeostasis insulin resistance index (Homa-IR) and insulin sensitivity index(ISI) were calculated.And then,the relationship between serum adiponectin levels and Insulin resistance(IR) wil be analysed.Results 1.The serum level of adiponectin was significantly lower in metabolic syndrome without diabetes group than in normal control group (1.15±0.81mg/l,4.81±1.20 mg/1,P0.01 =).2.The serum adiponectin level was negatively correlated with Homa-IR(P0.01).and positively correlated with ISI through linear correlation analysis(P0.01).However,the serum adiponectin level was only negatively correlated with Homa-IR through multiple linear regression analysis.Conclusions The level of serum adiponectin in metabolic syndrome cases without diabetes was significantly decreased.The serum adiponectin level was negatively correlated with Homa-IR.This shows that level of serum adiponectin was correlated with metabolic syndrome and insulin resistance.
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Adiponectin receptor 1
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