OBJECTIVEBetatrophin, a newly identified hormone, has been recently characterized as a potent stimulator that increases the production and expansion of insulin-secreting b-cells in mice, but the physiological role of betatrophin remains poorly understood. This study measured for the first time serum betatrophin levels in newly diagnosed patients with type 2 diabetes (T2DM) and explored the correlations between its serum levels and various metabolic parameters in T2DM. RESEARCH DESIGN AND METHODSWe analyzed the concentrations of betatrophin by ELISA in blood samples of 166 well-characterized individuals in whom anthropometric parameters, oral glucose tolerance test (OGTT), glycosylated hemoglobin, blood lipids, insulin sensitivity (1/homeostasis model assesment of insulin resistance [1/HOMA-IR] and Matsuda index [ISI M ]), and insulin secretion were measured. The participants were divided into newly diagnosed T2DM patients (n = 83) and age-, sex-and BMI-matched healthy control subjects (n = 83). RESULTSSerum betatrophin levels were significantly higher in T2DM patients than in healthy control subjects (613.08 [422.19-813.08] vs. 296.57 [196.53-509.46] pg/mL; P < 0.01). Serum betatrophin positively correlated with age, 2-h post-OGTT glucose (2hPG), and postprandial serum insulin (PSI), but negatively with 1/HOMA-IR and ISI M in T2DM patients. In the control group, betatrophin was only positively associated with age. In T2DM subjects, multivariate regression analyses showed that age, 2hPG, and PSI were independent factors influencing serum betatrophin levels. CONCLUSIONSCirculating concentrations of betatrophin are significantly increased in T2DM patients. Our results suggest that betatrophin may play a role in the pathogenesis of T2DM.Precise regulation of b-cell function is crucial for maintaining blood glucose homeostasis (1). In type 2 diabetes (T2DM), ambient insulin resistance forces b-cells to produce more insulin, which ultimately results in exhaustion of insulin production secondary to deterioration of b-cell functions. Unfortunately, neither pharmacotherapy nor insulin injections can reverse ongoing failure of b-cell function to prevent uncontrolled hyperglycemia and the devastating microvascular, neurologic, and macrovascular complications of diabetes. Treatments that replenish b-cell

Serum oxytocin levels were decreased in T2DM as well as OB subjects.

No abstract

No abstract

No abstract

The improved effects of dietary chickpeas on visceral adiposity, dyslipidaemia and insulin resistance were examined. Rats were fed a normal-fat diet (NFD), a high-fat diet (HFD) or a high-fat plus chickpea diet (HFD þ CP) for 8 months. The epididymal fat pad weight v. total body weight of rats was higher in the HFD group (0·032 (SD 0·0042) g/g) than in the NFD group (0·015 (SD 0·0064) g/g) and smaller in the HFD þ CP group (0·023 (SD 0·0072) g/g) compared with the HFD group (P, 0·05). Chickpea treatment also induced a favourable plasma lipid profile reflecting decreased TAG, LDL-cholesterol (LDL-C) and LDL-C:HDL-cholesterol levels (P, 0·05). HFD-fed rats had higher TAG concentration in muscle and liver, whereas the addition of chickpeas to the HFD drastically lowered TAG concentration (muscle, 39 %; liver, 23 %). The activities of lipoprotein lipase (LPL) in epididymal adipose tissue and hepatic TAG lipase in liver recorded a 40 and 23 % increase respectively in HFD rats compared with those in NFD rats; dietary chickpeas completely normalised the levels. Furthermore, chickpea-treated obese rats also showed a markedly lower leptin and LPL mRNA content in epididymal adipose tissue. An insulin tolerance test, oral glucose tolerance test and insulinreleasing test showed that chickpeas significantly improved insulin resistance, and prevented postprandial hyperglycaemia and hyperinsulinaemia induced by the chronic HFD. The present findings provide a rational basis for the consumption of chickpeas as a functional food ingredient, which may be beneficial for correcting dyslipidaemia and preventing diabetes. Chickpeas: Visceral adiposity: Dyslipidaemia: Insulin resistanceObesity is the most common nutritional disorder in the developed world and is a strong risk factor for hypertension, hyperlipidaemia, CVD and type 2 diabetes mellitus, which are closely linked with insulin resistance, and collectively called the metabolic syndrome 1 . Obesity causes excess fat accumulation not only in adipocytes but also ectopically in tissues such as muscle, liver, b cells and others, predisposing to the development of insulin resistance. Especially, skeletal muscle is a major site for insulin-stimulated glucose disposal 2 and the accumulation of TAG within lipid droplets in skeletal muscle is positively correlated to the severity of insulin resistance 3,4 .Recently, there has been growing interest in the use of medical plants and health foods for the treatment and prevention of disease 5,6 . Therefore, studies on obesity and diabetes as lifestyle-related diseases have focused on the search of functional food ingredients that suppress the accumulation of body fat and improve lipid metabolism 7 -9 , effects that, in turn, are beneficial for the amelioration of insulin resistance and prevention of type 2 diabetes.The chickpea (Cicer arietinum L.) is one of the world's most important legume crops as it contains approximately 50 % available carbohydrate, primarily in the form of starch, and 6·4 % fat, of which most is unsaturated (for examp...

A series of clinical trials and animal experiments have demonstrated that ginseng and its major active constituent, ginsenosides, possess glucose-lowering action. In our previous study, ginsenoside Rb 1 has been shown to regulate peroxisome proliferator-activated receptor g activity to facilitate adipogenesis of 3T3-L1 cells. However, the effect of Rb 1 on glucose transport in insulin-sensitive cells and its molecular mechanism need further elucidation. In this study, Rb 1 significantly stimulated basal and insulin-mediated glucose uptake in a time-and dose-dependent manner in 3T3-L1 adipocytes and C2C12 myotubes; the maximal effect was achieved at a concentration of 1 mM and a time of 3 h. In adipocytes, Rb 1 promoted GLUT1 and GLUT4 translocations to the cell surface, which was examined by analyzing their distribution in subcellular membrane fractions, and enhanced translocation of GLUT4 was confirmed using the transfection of GLUT4-green fluorescence protein in Chinese Hamster Ovary cells. Meanwhile, Rb 1 increased the phosphorylation of insulin receptor substrate-1 and protein kinase B (PKB), and stimulated phosphatidylinositol 3-kinase (PI3K) activity in the absence of the activation of the insulin receptor. Rb 1 -induced glucose uptake as well as GLUT1 and GLUT4 translocations was inhibited by the PI3K inhibitor. These results suggest that ginsenoside Rb 1 stimulates glucose transport in insulin-sensitive cells by promoting translocations of GLUT1 and GLUT4 by partially activating the insulin signaling pathway. These findings are useful in understanding the hypoglycemic and anti-diabetic properties of ginseng and ginsenosides.

During conversion of preadipocytes to adipocytes, growth arrest and subsequent activation of adipocyte genes by the transcription factors, CaEBPa a and PPARg g, lead to adipogenesis. During differentiation, these cells not only start expressing those genes necessary for adipocyte function, but also undergo changes in morphology to become rounded lipid ®lled adipocytes. Various factors in cell ± cell communication or cell ± matrix interaction may govern whether preadipocytes are kept in an undifferentiated state or undergo differentiation. In an attempt to identify molecules that play critical roles in the conversion of preadipocytes to adipocytes, we cloned by differential screening several regulatory molecules, including pref-1. Pref-1 is an inhibitor of adipocyte differentiation and is synthesized as a plasma membrane protein containing 6 EGF-repeats in the extracellular domain. Pref-1 is highly expressed in 3T3-L1 preadipocytes, but is not detectable in mature fat cells. Dexamethasone, a component of standard differentiation agents, inhibits pref-1 transcription and thereby promotes adipogenesis. Downregulation of pref-1 is required for adipose conversion and constitutive expression of pref-1 inhibits adipogenesis. Conversely, decreasing pref-1 levels by antisense pref-1 transfection greatly enhances adipogenesis. The ectodomain of pref-1 is cleaved to generate a biologically active 50 kDa soluble form. There are four major forms of membrane pref-1 resulting from alternate splicing. Two of these forms which have a deletion that includes the putative processing site proximal to the membrane do not produce a biologically active soluble form. This indicates that alternate splicing may determine the range of action, juxtacrine or paracrine, of pref-1.