Diabetes and bone metabolism

In the past decade several novel findings point to the critical role of the skeleton in several homeostatic processes, including energy balance. The connection begins in the bone marrow with lineage allocation of mesenchymal stem cells to adipocytes or osteoblasts. Osteoblasts and adipocytes produce factors affecting insulin homeostasis. The hormonally active adipose tissue can regulate bone metabolism. In this review authors discuss targets taking critical part in the bone-fat network: leptin, osteocalcin, PPAR γ2 and the Wnt/beta catenin pathway. Leptin regulates energy metabolism through controlling appetite. Mutation of the leptin gene resulting leptin resistance leads to high leptin levels, enormous appetite and pathologic obesity. Leptin also can influence the bone mass. The main effects of the thiazolidinedions - PPARγ agonists - are mediated through receptors located in adipocytes. However, beside their positive effects, they also suppress osteoblastogenesis and increase the risk for pathologic fractures. Osteocalcin, a known marker of bone formation, produced by osteoblasts decreases fat mass, promotes adiponectin production and insulin sensitivity, increases the number of pancreatic β-cells and increases insulin secretion. Thus, the skeletal system can regulate glucose metabolism and this substantially changed our view on this issue. Novel molecules can now be tested as targets in order to enhance bone formation and possibly prevent fractures.     

Fructose,weight gain,and the insulin resistance syndrome

This review explores whether fructose consumption might be a contributing factor to the development of obesity and the accompanying metabolic abnormalities observed in the insulin resistance syndrome. The per capita disappearance data for fructose from the combined consumption of sucrose and high-fructose corn syrup have increased by 26%, from 64 g/d in 1970 to 81 g/d in 1997. Both plasma insulin and leptin act in the central nervous system in the long-term regulation of energy homeostasis. Because fructose does not stimulate insulin secretion from pancreatic beta cells, the consumption of foods and beverages containing fructose produces smaller postprandial insulin excursions than does consumption of glucose-containing carbohydrate. Because leptin production is regulated by insulin responses to meals, fructose consumption also reduces circulating leptin concentrations. The combined effects of lowered circulating leptin and insulin in individuals who consume diets that are high in dietary fructose could therefore increase the likelihood of weight gain and its associated metabolic sequelae. In addition, fructose, compared with glucose, is preferentially metabolized to lipid in the liver. Fructose consumption induces insulin resistance, impaired glucose tolerance, hyperinsulinemia, hypertriacylglycerolemia, and hypertension in animal models. The data in humans are less clear. Although there are existing data on the metabolic and endocrine effects of dietary fructose that suggest that increased consumption of fructose may be detrimental in terms of body weight and adiposity and the metabolic indexes associated with the insulin resistance syndrome, much more research is needed to fully understand the metabolic effect of dietary fructose in humans.     

Effects of visceral fat accumulation in obesity and type 2 diabetes

Type 2 diabetes has become the most frequently encountered metabolic disorder in the world and obesity, meaning visceral adiposity, is the core problem. In the abdominal adipose tissue, insulin resistance (IR) reduces the antilipolytic effect of insulin, which in turn leads to reduced glucose uptake and increased release of free fatty acids (FFAs) and glycerol. Chronic exposure of beta cells to elevated FFA levels causes detrimental consequences such as increased insulin secretion at low glucose concentrations, decreased proinsulin biosynthesis, depletion of insulin reserves and reduced response to concentrations of glucose stimulus. Adipose peroxisome proliferator-activated receptors (PPAR)-γ appears to be an essential mediator for the maintenance of whole-body insulin sensitivity that protects non-adipose tissue against lipid overload. Current data suggest that PPAR-γ-activating ligands improve adipose tissue function, and may prevent the progression of IR to diabetes and also endothelial dysfunction to atherosclerosis. Links between environmental influences, the layout of visceral fat, the PPARs, the adiponectin and the adipocytokines still need to be completely clarified.     

Regulation of leptin production in humans

Serum levels of the adipocyte hormone leptin are increased in proportion to body fat stores as a result of increased production in enlarged fat cells from obese subjects. In vitro studies indicate that insulin and glucocorticoids work directly on adipose tissue to upregulate in a synergistic manner leptin mRNA levels and rates of leptin secretion in human adipose tissue over the long term. Thus, the increased leptin expression observed in obesity could result from the chronic hyperinsulinemia and increased cortisol turnover. Superimposed upon the long-term regulation, nutritional status can influence serum leptin over the short term, independent of adiposity. Fasting leads to a gradual decline in serum leptin that is probably attributable to the decline in insulin and the ability of catecholamines to decrease leptin expression, as observed in both in vivo and in vitro studies. In addition, increases in serum leptin occur approximately 4-7 h after meals. Increasing evidence indicates that insulin, in concert with permissive effects of cortisol, can increase serum leptin over this time frame and likely contributes to meal-induced increases in serum leptin. Further research is required to elucidate the cellular and molecular mechanisms underlying short- and long-term nutritional and hormonal regulation of leptin production and secretion.     

Adiponectin: novelties in metabolism and hormonal regulation

Adiponectin is a protein secreted exclusively by white adipose tissues and is abundantly present in human plasma. Adiponectin was found decreased in obese and diabetes mellitus type 2 patients and increased with weight reduction. A negative correlation between circulating adiponectin levels and body mass index and insulin resistance has been demonstrated. Plasma adiponectin concentrations were found lower in diabetes mellitus type 2 patients with coronary artery disease. Moreover, studies in aortic endothelial cells revealed that the protein exerts a dose-dependent decrease of the surface expression of vascular adhesion molecules and cytokine production from macrophages, suggesting the implication of adiponectin in atherosclerosis and inflammation. Weight loss and treatment with thiazolidinediones stimulate endogenous adiponectin production. Peripheral administration of adiponectin leads to reduction of visceral adiposity and increase of free fatty acid oxidation and insulin resistance. Furthermore, it enhances the expression of uncoupling proteins and sympathetic nerve activity in adipose tissues. Experimental studies in mice have shown that intraperitoneal administration of adiponectin lowers plasma glucose. These data show adiponectin to be an important factor in the issue of obesity and its associated disorders, and indicate a potential future utilization of adiponectin as a drug in the treatment of metabolic syndrome.     

Norepinephrine- and epinephrine-deficient mice gain weight normally on a high-fat diet

OBJECTIVE: Signaling through adrenergic receptors (ARs) by norepinephrine (NE) and epinephrine (Epi) regulates weight gain when mice are fed a high-fat diet (HFD) by controlling diet-induced thermogenesis. Thus, one would predict that mice unable to make NE/Epi because of inactivation of the dopamine beta-hydroxylase gene (Dbh-null mice) would have a propensity to become obese. We characterized the response of Dbh-null and control mice to a HFD. RESEARCH METHODS AND PROCEDURES: Dbh-null and control mice were fed an HFD or a regular diet (RD) for 2 months. Body weight, adiposity, muscle triglyceride levels, and adipocyte size were measured, as were circulating leptin, adiponectin, triglyceride, glucose, and insulin levels. A glucose tolerance test was also preformed. RESULTS: Dbh-null mice gain weight normally on an HFD and have the same adiposity. Their serum triglyceride and leptin levels are normal, but adipocytes are approximately 30% smaller than controls. Dbh-null mice maintain low blood glucose levels and glucose tolerance when exposed to the HFD in contrast to controls. DISCUSSION: Complete lack of NE/Epi does not predispose to obesity. Because mice lacking all three betaARs become obese on an HFD, an imbalance of signaling through alpha- and betaARs seems to be responsible for obesity. Surprisingly, Dbh-null mice maintain glucose tolerance.     

Adiponectin: Novelties in Metabolism and Hormonal Regulation

Abstract

Adiponectin is a protein secreted exclusively by white adipose tissues and is abundantly present in human plasma. Adiponectin was found decreased in obese and diabetes mellitus type 2 patients and increased with weight reduction. A negative correlation between circulating adiponectin levels and body mass index and insulin resistance has been demonstrated. Plasma adiponectin concentrations were found lower in diabetes mellitus type 2 patients with coronary artery disease. Moreover, studies in aortic endothelial cells revealed that the protein exerts a dose-dependent decrease of the surface expression of vascular adhesion molecules and cytokine production from macrophages, suggesting the implication of adiponectin in atherosclerosis and inflammation. Weight loss and treatment with thiazolidinediones stimulate endogenous adiponectin production. Peripheral administration of adiponectin leads to reduction of visceral adiposity and increase of free fatty acid oxidation and insulin resistance. Furthermore, it enhances the expression of uncoupling proteins and sympathetic nerve activity in adipose tissues. Experimental studies in mice have shown that intraperitoneal administration of adiponectin lowers plasma glucose. These data show adiponectin to be an important factor in the issue of obesity and its associated disorders, and indicate a potential future utilization of adiponectin as a drug in the treatment of metabolic syndrome.     

Adipokines as uremic toxins

The adipose tissue has pleiotropic functions far beyond the mere storage of energy, and it secretes a number of hormones and cytokines, called adipokines, which have biological effects that impact heath and disease. Adipokines are markedly elevated in the plasma of uremic patients, mainly due to decreased renal excretion. They have pluripotent signaling effects on inflammation/oxidative stress (leptin, adiponectin, resistin), protein-energy wasting (leptin, adiponectin), insulin signaling (adiponectin, leptin, visfatin), endothelial dysfunction (visfatin), and vascular damage (adiponectin, leptin, resistin), which are prevalent in uremic patients. Obesity superimposed to uremia may further aggravate hyperadipokinemia, with the exception of adiponectinemia, which is mitigated by adiposity. Among adipokines and until more data become available, only leptin may be considered as a full uremic toxin owing to adverse effects on protein-energy wasting, cardiovascular damage, inflammation, and the immune system, which have been documented both clinically and experimentally. Resistin and visfatin display some features of uremic toxins, but more data are needed to consider these adipokines as true uremic toxins. In contrast, high levels of adiponectin and chemerin seen in uremia appear to be beneficial. Further research is needed to investigate whether selective removal of leptin, resistin, and visfatin and increments of adiponectin and chemerin levels may have clinical relevance in uremic patients.     

孕晚期妊娠糖尿病脂联素、瘦素与胰岛素抵抗的相关性

目的探讨孕晚期妊娠糖尿病（GDM）患者脂联素（ADP）、瘦素（LEP）与胰岛素抵抗（IR）的关系。方法选取166例28～32周孕妇,其中84例GDM患者（GDM组）、82例糖耐量正常（NGT组）,检测血清胰岛素、ADP和LEP水平,同时计算HOMA胰岛素抵抗指数（HOMA-IR）及胰岛素敏感指数（ISOGTT）以评价胰岛素敏感性,计算β细胞功能指数（HBCI）和30 min净增胰岛素/30 min净增血糖比值（ΔI30/ΔG30）以评价胰岛素分泌功能。结果 （1）GDM组空腹胰岛素（FIns）明显高于NGT组（P〈0.01）,HOMA-IR也明显高于NGT组（P〈0.05）;GDM组ISOGTT低于NGT组（P〈0.01）;GDM组HBCI低于NGT组（P〈0.01）,ΔI30/ΔG30也低于NGT组（P〈0.05）。（2）GDM组ADP水平低于NGT组（P〈0.01）,而LEP水平高于NGT组（P〈0.01）。（3）GDM组多元线性逐步回归分析结果显示ADP、LEP是影响孕晚期GDM患者IR的独立危险因素。结论孕晚期GDM患者ADP减少、LEP升高与IR密切相关。     

Role of adipose tissue in body-weight regulation: mechanisms regulating leptin production and energy balance

Adipose tissue performs complex metabolic and endocrine functions. Among the endocrine products produced by adipose tissue are tumour necrosis factor alpha, interleukin 6, acylation-stimulating protein and leptin. The present review will focus primarily on mechanisms regulating leptin production and leptin action, and the implications of this regulation in the control of energy balance. Leptin acts in the central nervous system where it interacts with a number of hypothalamic neuropeptide systems to regulate feeding behaviour and energy expenditure. The presence of extreme obesity in animals and human subjects with mutations of the leptin gene or the leptin receptor demonstrates that normal leptin production and action are critical for maintaining energy balance. Insulin is the major regulator of leptin production by adipose tissue. Insulin infusions increase circulating leptin concentrations in human subjects. Plasma leptin levels are markedly decreased in insulin-deficient diabetic rodents, and the low leptin levels contribute to diabetic hyperphagia. Based on in vitro studies, the effect of insulin to stimulate leptin production appears to involve increased glucose metabolism. Blockade of glucose transport or glycolysis inhibits leptin expression and secretion in isolated adipocytes. Evidence suggests that anaerobic metabolism of glucose to lactate does not stimulate leptin production. Alterations in insulin-mediated glucose metabolism in adipose tissue are likely to mediate the effects of energy restriction to decrease, and refeeding to increase, circulating leptin levels. Changes in glucose metabolism may also explain the observation that high-fat meals lower 24h circulating leptin levels relative to high-carbohydrate meals in human subjects, suggesting a mechanism that may contribute to the effects that high-fat diets have in promoting increased energy intake, weight gain and obesity. The decreased circulating leptin observed during energy restriction is related to increased sensations of hunger in human subjects. Thus, decreases in leptin during energy-restricted weight-loss regimens may contribute to the strong propensity for weight regain. A better understanding of the precise mechanisms regulating leptin production and leptin action may lead to new approaches for managing obesity.     

Anti-diabetic effects including diabetic nephropathy of anti-osteoporotic trace minerals on diabetic mice

Objective

In our previous study to evaluate the effects of soluble silicon (Si) on bone metabolism, Si and coral sand (CS) as a natural Si-containing material suppressed peroxisome proliferator-activated receptor γ (PPARγ), which regulates both glucose and bone metabolism and increases adipogenesis at the expense of osteogenesis, leading to bone loss. In this study, we investigated the anti-diabetic effects of bone-seeking elements, Si and stable strontium (Sr), and CS as a natural material containing these elements using obese diabetic KKAy mice.

Methods

Weanling male mice were fed diets containing 1% Ca supplemented with CaCO₃ as the control and CS, and diets supplemented with 50 ppm Si or 750 ppm Sr to control diet for 56 d. The mRNA expressions related to energy expenditure in the pancreas and kidney were quantified by real-time polymerase chain reaction.

Results

At the end of feeding, plasma glucose, insulin, leptin, and adiponectin levels decreased significantly in three test groups, while pancreatic PPARγ and adiponectin mRNA expression levels increased significantly toward the normal level, improving the glucose sensitivity of β-cells and inducing a significant decrease in insulin expression. The renal PPARγ, PPARα, and adiponectin expression levels, histologic indices of diabetic glomerulopathy, and plasma indices of renal function were also improved significantly in the test groups.

Conclusion

Taken together, anti-osteoporotic trace minerals, Si and Sr, and CS containing them showed novel anti-diabetic effects of lowering blood glucose level, improving the tolerance to insulin, leptin, and adiponectin, and reducing the risk of glomerulopathy through modulation of related gene expression in the pancreas and kidney.     

Young overweight and obese women with lower circulating osteocalcin concentrations exhibit higher insulin resistance and concentrations of C-reactive protein

The role of the skeleton in the regulation of energy metabolism in humans is not clear. This study investigates the hypothesis that biomarkers of bone turnover are associated with indices of glucose homeostasis and systemic inflammation in young adults. A cross-sectional study investigating the relationships between biomarkers of bone turnover (serum total and uncarboxylated osteocalcin, bone-specific alkaline phosphatase, C-telopeptide of type I collagen, urinary N-telopeptide of type I collagen) and glucose metabolism (fasting plasma glucose [FPG], insulin, insulin resistance [homeostatic model assessment of insulin resistance]), systemic inflammation (high-sensitivity C-reactive protein [hsCRP] and interleukin-6), adipokines (leptin and adiponectin), and body composition was conducted in 268 young, nondiabetic overweight and obese adults aged 20 to 40 years (116 men, 152 women; body mass index, 27.5-32.5 kg/m²). Data on diet, physical activity, serum 25-hydroxyvitamin D, and parathyroid hormone were also collected. In women, there was a stepwise increase in lean body mass (P < .05) and a decrease in serum hsCRP (P < .001) across tertiles of total osteocalcin. Multiple linear regression analysis showed significant inverse associations between total osteocalcin and FPG (β = −0.350; P = .016; 95% confidence interval [CI], −0.35 to −0.04), insulin (β = −0.455; P = .002; 95% CI, −1.9 to −0.46), and homeostatic model assessment of insulin resistance (β = −0.508; P = .001; 95% CI, −10.93 to −3.17) in women with total osteocalcin concentrations below the group median. Men in the lowest tertile of uncarboxylated osteocalcin had twice the concentration of hsCRP than did other men (P = .05). In this sample, women with less lean body mass had lower circulating total osteocalcin concentrations and exhibited higher FPG, insulin resistance, and hsCRP compared with their similarly sized counterparts, suggesting that associations between osteocalcin and systemic inflammation, glucose homeostasis, and insulin resistance may be influenced by differences in sex and body composition.     

A prospective study of maternal prenatal weight and offspring cardiometabolic health in midchildhood

PurposeTo examine the relations of maternal prepregnancy body mass index (ppBMI) and gestational weight gain (GWG) with offspring cardiometabolic health.DesignWe studied 1090 mother–child pairs in Project Viva, a Boston-area prebirth cohort. We measured overall (dual x-ray absorptiometry total fat; body mass index z-score) and central adiposity (dual x-ray absorptiometry trunk fat), and systolic blood pressure in offspring at 6 to 10 years. Fasting bloods (n = 687) were assayed for insulin and glucose (for calculation of homeostatic model assessment of insulin resistance), triglycerides, leptin, adiponectin, high sensitivity C-reactive protein, and interleukin 6. Using multivariable linear regression, we examined differences in offspring outcomes per 1 SD maternal ppBMI and GWG.ResultsAfter adjustment for confounders, each 5 kg/m² higher ppBMI corresponded with 0.92 kg (95% confidence interval, 0.70–1.14) higher total fat, 0.27 BMI z-score (0.21–0.32), and 0.39 kg (0.29–0.49) trunk fat. ppBMI was also positively associated with homeostatic model assessment of insulin resistance, leptin, high sensitivity C-reactive protein, interleukin 6, and systolic blood pressure; and lower adiponectin. Each 5 kg of GWG predicted greater adiposity (0.33 kg [0.11–0.54] total fat; 0.14 kg [0.04–0.23] trunk fat) and higher leptin (6% [0%–13%]) in offspring after accounting for confounders and ppBMI.ConclusionsChildren born to heavier mothers have more overall and central fat and greater cardiometabolic risk. Offspring of women with higher GWG had greater adiposity and higher leptin.     

儿童血清ghrelin水平与血脂、瘦素、脂联素及胰岛素关系的分析

目的探讨儿童血清ghrelin水平与血脂、瘦素、脂联素及胰岛素的关系。方法采用多阶段随机抽样的方法,随机抽取879名8～10岁小学生作为调查对象。测量身高、体重、腰围,计算体质指数(BMI)、体脂百分比(%BF),测定血清总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)、空腹血糖、ghrelin、脂联素、胰岛素及瘦素。结果随血清ghrelin水平的升高,体重、腰围、BMI、%BF、血清瘦素水平逐渐降低(P<0.0001),血清HDL-C水平呈现逐渐增高的趋势(P<0.0001),血清TC、胰岛素和脂联素水平变化趋势不明显;与ghrelin密切相关的指标为体成分指标,包括身高、体重、腰围、BMI、%BF以及瘦素,其次是血脂代谢指标,包括TG、HDL-C、TC、LDL-C,第三是血糖代谢指标,包括空腹血糖和胰岛素。结论ghrelin与体成分指标、瘦素、脂联素、胰岛素以及血脂有不同程度的关联,但和身高、体重、腰围、BMI、%BF以及瘦素的相关最为密切。     

Effects of metformin and vanadium on leptin secretion from cultured rat adipocytes

OBJECTIVE: We have reported that glucose utilization regulates leptin expression and secretion from isolated rat adipocytes. In this study, we employed two antidiabetic agents that act to increase glucose uptake by peripheral tissues, metformin and vanadium, as pharmacological tools to examine the effects of altering glucose utilization on leptin secretion in primary cultures of rat adipocytes. RESEARCH METHODS AND PROCEDURES: Isolated adipocytes (100 microL of packed cells per well) were anchored in a defined matrix of basement membrane components (Matrigel) with media containing 5.5 mM glucose and incubated for 96 hours with metformin or vanadium. Leptin secretion, glucose utilization, and lactate production were assessed. RESULTS: Metformin (0.5 and 1.0 mM) increased glucose uptake in the presence of 0.16 nM insulin by 37 +/- 10% (p < 0.005) and 62 +/- 8% (p < 0.0001) over insulin alone, respectively. Metformin from 0.5 to 5.0 mM increased lactate production by 105 +/- 43% (p < 0.025) to 202 +/- 52% (p < 0.0025) and at 1.0 and 5.0 mM increased the proportional rate of glucose conversion to lactate by 78 +/- 18% (p < 0.005) and 166 +/- 41% (p < 0.0025), respectively. At concentrations less than 0.5 mM, metformin did not affect leptin secretion, but at 0.5 mM, the only concentration that significantly increased glucose utilization without increasing glucose conversion to lactate, leptin secretion was modestly stimulated (by 20 +/- 9%; p < 0.05). Concentrations from 1.0 to 25 mM inhibited leptin secretion by 25 +/- 8% (p < 0.005) to 89 +/- 4% (p < 0.0001). Across metformin doses, leptin secretion was inversely related to the percentage of glucose taken up and released as lactate (r = -0.74; p < 0.0001). Vanadium (5 to 20 microM) increased glucose uptake from 20 +/- 7% (p < 0.01) to 34 +/- 13% (p < 0.02) and increased lactate production at 5 microM by 17 +/- 8% (p < 0.025) and 10 microM by 61 +/- 20% (p < 0.02) but did not alter the conversion of glucose to lactate. Vanadium (5 to 50 microM) inhibited leptin secretion by 33 +/- 6% (p < 0.0025) to 61 +/- 8% (p < 0.0001). DISCUSSION: Both metformin and vanadium increase glucose uptake and inhibit leptin secretion from cultured adipocytes. The inhibition of leptin secretion by metformin is related to an increase in the metabolism of glucose to lactate. The inhibition by vanadium most likely involves direct effects on cellular phosphatases. We hypothesize that the effect of glucose utilization to stimulate leptin production involves the metabolism of glucose to a fate other than anaerobic lactate production, possibly oxidation or lipogenesis.     

The effects of obesity-associated insulin resistance on mRNA expression of peroxisome proliferator-activated receptor-gamma target genes, in dogs

Visceral adipose tissue and skeletal muscle have central roles in determining whole-body insulin sensitivity. The peroxisome proliferator-activated receptor-gamma (PPARgamma) is a potential mediator of insulin sensitivity. It can directly modulate the expression of genes that are involved in glucose and lipid metabolism, including GLUT4, lipoprotein lipase (LPL) and adipocytokines (leptin and adiponectin). In this study, we aimed to determine the effects of obesity-associated insulin resistance on mRNA expression of PPARgamma and its target genes. Dogs were studied when they were lean and at the end of an overfeeding period when they had reached a steady obese state. The use of a sensitive, real-time PCR assay allowed a relative quantification of mRNA expression for PPARgamma, LPL, GLUT4, leptin and adiponectin, in adipose tissue and skeletal muscle. In visceral adipose tissue and/or skeletal muscle, mRNA expression of PPARgamma, LPL and GLUT4 were at least 2-fold less in obese and insulin-resistant dogs compared with the same animals when they were lean and insulin-sensitive. The mRNA expression and plasma concentration of leptin was increased, whereas the plasma level and mRNA expression of adiponectin was decreased, by obesity. In adipose tissue, PPARgamma expression was correlated with leptin and adiponectin. These findings, in an original model of obesity induced by a prolonged period of overfeeding, showed that insulin resistance is associated with a decrease in PPARgamma mRNA expression that could dysregulate expression of several genes involved in glucose and lipid metabolism.     

血清脂肪细胞因子与妊娠期糖尿病关系的研究

目的:探讨妊娠期糖尿病(GDM)孕妇血清脂肪因子脂联素、瘦素、肿瘤坏死因子(TNF-α)水平变化及其与胰岛素抵抗的相关性。方法:随机抽取孕周15～20周的孕妇测定空腹血糖(FBG)、空腹胰岛素(FINS)、血脂联素、瘦素、TNF-α水平,孕24～28周行OGTT检查,按结果分为3组,糖耐量正常组(NGT)59例,GDM组41例,GIGT组50例,比较各组胰岛素抵抗指数(HOMA-IR)、胰岛素分泌指数(HBCI)及孕前、孕中期的BMI的差异,分析血脂联素、瘦素、TNF-α与IR的关系。结果:①GDM组及GIGT组HOMA-IR较NGT组明显升高,差异有统计学意义(P<0.05),3组间HBCI比较差异无统计学意义(P>0.05)。②GDM组及GIGT组血清脂联素水平显著低于NGT组(P<0.05),血清瘦素水平及TNF-α水平则显著高于NGT组(P<0.05)。③脂联素与HOMA-IR呈负相关,相关系数为-0.65;而瘦素、TNF-α与HOMA-IR呈正相关,相关系数分别为0.58、0.47。结论:妊娠期糖尿病血清脂联素、瘦素、TNF-α水平的改变与妊娠期胰岛素抵抗有关,可作为GDM的重要预测因子。     

Sexual dimorphism and regulation of resistin, adiponectin, and leptin expression in the mouse

OBJECTIVE: To examine gender differences and hormonal regulation of resistin, adiponectin, and leptin. RESEARCH METHODS AND PROCEDURES: Plasma levels were measured, and mRNA expression in perigonadal fat was quantified by RNase protection assays. RESULTS: Plasma resistin declined with age despite an increase in adiposity in both genders. In male mice, plasma leptin increased, whereas adiponectin levels were constant. In females, both adiponectin and leptin levels increased with age. Resistin mRNA levels were significantly higher in female than male mice at all ages, whereas leptin and adiponectin mRNA levels were similar in fat from 6-week-old male and female mice, and sexual dimorphism was apparent only in the older mice, with higher levels apparent in females. Castration did not abolish gender differences in plasma levels or resistin, adiponectin, or leptin mRNAs. Castration of male mice did not significantly change adipokine mRNA levels or plasma levels of resistin or leptin; however, adiponectin was significantly increased. Dihydrotestosterone treatment had no effect on adipokine mRNA expression or resistin and adiponectin levels but increased leptin levels. In contrast, ovariectomy significantly increased resistin mRNA abundance and decreased leptin and adiponectin mRNAs. Plasma leptin levels were also increased by ovariectomy, whereas resistin and adiponectin levels were unchanged. Estrogen replacement significantly reduced resistin mRNA and increased leptin and adiponectin mRNA levels but had no effect on plasma adipokine levels. DISCUSSION: The gender differences in adipokine mRNA expression and plasma levels were not ablated by castration and seem to be dependent on other factors in addition to gonadal steroids.     

Adiponectin in relation to malignancies: a review of existing basic research and clinical evidence

Adiponectin, an adipocyte-secreted hormone that plays an important role in diabetes and cardiovascular disease, may also be of importance in the development and progression of several malignancies. Circulating adiponectin concentrations, which are determined mainly by genetic factors, nutrition, and adiposity, are lower in patients with breast, endometrial, prostate, and colon cancer. It has thus been proposed that adiponectin may be a biological link between obesity (especially central obesity) and increased cancer risk. Adiponectin may influence cancer risk through its well-recognized effects on insulin resistance, but it is also plausible that adiponectin acts on tumor cells directly. Several cancer cell types express adiponectin receptors that may mediate the effects of adiponectin on cellular proliferation. Herein, we review recent evidence supporting a role of serum adiponectin concentrations as a novel risk factor and possible diagnostic marker for obesity-related malignancies, including cancers of the breast, endometrium, colon, and prostate. Further studies are needed to fully elucidate the potential role of adiponectin in cancer diagnostics and therapeutics.     

矢车菊素-3-葡萄糖苷对肥胖大鼠低度炎症反应及胰岛素敏感性的影响

目的 观察矢车菊素-3-葡萄糖苷(cyanidin-3-glucoside, C3G)对肥胖大鼠血清炎症因子(TNF-α、IL-6和MCP-1)及胰岛素敏感性的影响。方法 3周龄雄性SD大鼠30只, 随机分为对照组(n=8)和高脂饮食组(n=22), 分别予以普通饲料及高脂饲料喂养5周。肥胖造模成功的17只大鼠再随机分为肥胖组(n=8)和C3G组(n=9)。C3G组予C3G 100 mg/(kg·d)灌胃, 其余组予等量生理盐水灌胃。实验结束时准确称量大鼠体重及内脏脂肪质量, 全自动生化分析仪测定空腹血糖(fasting glucose, FPG), 放免法测血清胰岛素(fasting insulin, FINS), ELISA测血清脂联素及TNF-α、IL-6、MCP-1水平, 并计算内脏脂肪比和胰岛素敏感指数(insulin sensitivity index, IAI)。结果 肥胖组和C3G组大鼠体重、内脏脂肪比和血清TNF-α、IL-6、MCP-1水平明显高于对照组(P均<0.05), 而C3G组上述指标明显低于肥胖组(P均<0.05)。肥胖组和C3G组血清脂联素水平及IAI明显低于对照组(P均<0.05), 而C3G组上述指标明显高于肥胖组上述指标。结论 C3G能明显增加肥胖大鼠的胰岛素敏感性, 其可能与增加血清脂联素水平及降低血清炎症因子(TNF-α、IL-6、MCP-1)水平有关。