Adipokines, the bioactive factors derived mainly from adipocytes, regulate pancreatic beta-cell function including insulin secretion, gene expression and apoptosis. In this review, we propose that adipokines influence beta-cell function through three interdependent pathways. The first is through regulating lipid and glucose metabolism in beta-cells. The second implicates the change of ion channel opening and closing in beta-cells. The third pathway is via the modification of insulin sensitivity of beta-cells. The endocrine function of adipocytes is dynamic, and the secretion of various adipokines changes under different metabolic conditions. During the progression from the normal state to obesity and to type 2 diabetes, adipokines contribute to the occurrence and development of beta-cell dysfunction in type 2 diabetes.
Adipocytes ; physiology ; Adiponectin ; physiology ; Animals ; Diabetes Mellitus, Type 2 ; physiopathology ; Glucose ; metabolism ; Humans ; Insulin ; pharmacology ; Insulin-Secreting Cells ; physiology ; Leptin ; physiology ; Lipid Metabolism

PURPOSE: Obesity is a major risk factor for asthma and it influences airway smooth muscle function and responsiveness. Adiponectin is inversely associated with obesity and its action is mediated through at least 2 cell membrane receptors (AdipoR1 and AdipoR2). Leptin is positively associated with obesity. We investigated whether human airway smooth muscle (ASM) cells express adiponectin receptors and whether adiponectin and leptin regulate human ASM cell proliferation and vascular endothelial growth factor (VEGF) release. MATERIALS AND METHODS: Human ASM cells were growth-arrested in serum-deprived medium for 48 hours and then stimulated with PDGF, adiponectin and leptin. After 48 hours of stimulation, proliferation was determined using a cell proliferation ELISA kit. Human AdipoR1 and -R2 mRNA expressions were determined by RT-PCR using human-specific AdipoR1 and -R2 primers. Concentrations of VEGF, monocyte chemotactic protein (MCP)-1 and macrophage inflammatory protein (MIP)-1alpha in cell culture supernatant were determined by ELISA. RESULTS: Both AdipoR1 and AdipoR2 mRNA were expressed in the cultured human ASM cells. However, adiponectin did not suppress PDGF-enhanced ASM cell proliferation, nor did leptin promote ASM cell proliferation. Leptin promoted VEGF release by human ASM cells, while adiponectin did not influence VEGF release. Neither leptin nor adiponectin influenced MCP-1 secretion from human ASM cells. Adiponectin and MIP-1alpha were not secreted by human ASM cells. CONCLUSION: Human ASM cells expressed adiponectin receptors. However, adiponectin did not regulate human ASM cell proliferation or VEGF release, while leptin stimulated VEGF release by human ASM cells.
Adiponectin/metabolism/*pharmacology/physiology ; Cell Proliferation/*drug effects ; Cells, Cultured ; Chemokine CCL2/metabolism ; Chemokine CCL3/metabolism ; Humans ; Leptin/metabolism/*pharmacology/physiology ; Myocytes, Smooth Muscle/cytology/drug effects/*metabolism ; Obesity/metabolism ; Platelet-Derived Growth Factor/metabolism ; Receptors, Adiponectin/*metabolism ; Respiratory System/cytology/metabolism ; Vascular Endothelial Growth Factor A/metabolism

OBJECTIVETo study the effect of a new obesity-related gene NYGGF4 on the insulin sensitivity and secretory function of adipocytes.

METHODS3T3-L1 preadipocytes transfected with either an empty expression vector (pcDNA3.1; control group) or an NYGGF4 expression vector (NYGGF4-pcDNA3.1) were cultured in vitro and differentiated into the matured adipocytes with the standard insulin plus dexamethasone plus 3-isobutyl-methylxanthine (MDI) induction cocktail. 2-deoxy-D-[3H] glucose uptake was determined by liquid scintillation counting. Western blot was performed to detect the protein content and translocation of glucose transporter 4 (GLUT4). The supernatant concentrations of TNF-alpha, IL-6, adiponectin and resistin were measured using ELISA.

RESULTSNYGGF4 over-expression in 3T3-L1 adipocytes reduced insulin-stimulated glucose uptake. NYGGF4 over-expression impaired insulin-stimulated GLUT4 translocation without affecting the total protein content of GLUT4. The concentrations of TNF-alpha, IL-6, adiponectin and resistin in the culture medium of 3T3-L1 transfected with NYGGF4 were not significantly different from those in the control group.

CONCLUSIONSNYGGF4 over-expression impairs the insulin sensitivity of 3T3-L1 adipocytes through decreasing GLUT4 translocation and had no effects on the secretory function of adipocytes.

3T3-L1 Cells ; Adipocytes ; drug effects ; secretion ; Adiponectin ; secretion ; Animals ; Carrier Proteins ; genetics ; physiology ; Glucose ; metabolism ; Glucose Transporter Type 4 ; analysis ; metabolism ; Insulin ; pharmacology ; Interleukin-6 ; secretion ; Mice ; Resistin ; analysis ; Transfection ; Tumor Necrosis Factor-alpha ; secretion

OBJECTIVETo study the effect of conjugated linoleic acid (CLA) on expression of adiponectin in white adipose tissue of obese rats.

METHODSMale Wistar rats were randomly divided into control group, high-fat group and high fat + CLA group (0.75 g, 1.50 g, 3.00 g per hundred gram diet weight), we observed the effect of CLA on serum insulin and glucose levels of obese rats, and the reverse transcription polymerase chain reaction (RT-PCR) technique was used to measure the expression level of adiponectin and peroxisome proliferator-activated receptor-gamma (PPARgamma) mRNA.

RESULTSThe serum insulin and glucose levels of obese rats were (11.11 +/- 2.73) microIU/ml, (5.09 +/- 0.66) mmol/L. The supplement of CLA decreased the hyperinsulinemia and hyperglycemia, the serum insulin in CLA group (0.75 g, 1.50 g, 3.00 g per hundred gram diet weight) were (6.99 +/- 1.77) microIU/ml, (7.36 +/- 1.48) microIU/ml, (7.85 +/- 1.60) microIU/ml (P < 0.05), and glucose were (4.28 +/- 0.72) mmol/L, (4.18 +/- 0.55) mmol/L (P < 0.05), (4.06 +/- 0.63) mmol/L (P < 0.05), CLA can increase the expression of adiponectin and PPARgamma in adipose tissue of obese rat.

CONCLUSIONThe CLA might improve the insulin resistance of the obese rat and increase the expression of adiponectin mRNA, which might possibly act through activating PPARgamma.

Adiponectin ; biosynthesis ; genetics ; Adipose Tissue ; metabolism ; Animals ; Insulin Resistance ; physiology ; Linoleic Acids, Conjugated ; pharmacology ; Male ; Obesity ; metabolism ; PPAR gamma ; biosynthesis ; genetics ; RNA, Messenger ; biosynthesis ; genetics ; Random Allocation ; Rats ; Rats, Wistar ; Reverse Transcriptase Polymerase Chain Reaction

OBJECTIVETo investigate the alteration of the adiponectin signal pathway in hypertrophic myocardium of spontaneous hypertensive rats (SHR) and to observe the effects of Gadol (GD) and Ganoderma spores (GS) on the hemodynamic parameters and the adiponectin signal pathway of SHR.

METHODSSHRs, 8 weeks old, were randomly divided into four groups: the untreated group, and the three treated groups treated with GD, GS, and GD + GS respectively by gastrogavage for 4 weeks. Controlled with 8-week-old WKY rats, the hemodynamic parameters in all rats were recorded through the carotid artery intubation; the serum level of adiponectin was determined with ELISA; the mRNA expressions of adiponectin receptors (AdipoRs) and carnitine palmitoyl transferase (CPT-1) were determined by RT-PCR; and the protein expression of adenosine monophosphate activated protein kinase (AMPK), both phosphorylated and un-phosphorylated, was detected by Western blot.

RESULTSCompared with the WKY rats, the systolic blood pressure (SBP), diastolic blood pressure (DBP) and myocardial hypertrophy index (MHI) in SHR were significantly higher; the serum levels of adiponectin and phosphorylated AMPK, mRNA expressions of AdipoR1 and CPT-1 in SHR heart tissue were lower (P < 0.05). Compared with the SHR, medication of GD and GS, either alone or in combination, could reduce SBP, DBP and MHI significantly (P < 0.01, P < 0.05), and elevate the mRNA expression of CPT-1 (P < 0.05) in heart, but levels of adiponectin, AdipoR1 and phosphorylated AMPK could only be raised by combined use of the two (P < 0.05).

CONCLUSIONSAdiponectin signal transduction pathway alteration presents in the myocardium of SHR, which might be one of the molecular mechanisms that cause hypertrophic metabolic abnormality. GD and GS could improve the hemodynamic index in SHR, and enhance the level of adiponectin and the expression of its related signal transduction molecules.

Adiponectin ; metabolism ; physiology ; Animals ; Cardiomyopathy, Hypertrophic ; etiology ; metabolism ; Drugs, Chinese Herbal ; pharmacology ; Ganoderma ; chemistry ; Hemodynamics ; drug effects ; Hypertension ; complications ; Male ; Random Allocation ; Rats ; Rats, Inbred SHR ; Rats, Inbred WKY ; Rhodiola ; chemistry ; Signal Transduction ; drug effects ; Spores

This study was performed to evaluate the contribution of adiponectin to the production of interleukin (IL)-6, IL-8, vascular endothelial growth factor (VEGF), matrix metalloproteinase (MMP)-1 and MMP-13 in human endothelial cells and osteoblasts in arthritic joints. Cultured human umbilical vascular endothelial cells (HUVECs) and osteoblasts were stimulated with adiponectin (1 or 10 mug ml-1) or IL-1beta (0.1 ng ml-1) in the presence or absence of hypoxia for 24 h. The protein expression patterns were examined by analyzing culture supernatants using the enzyme-linked immunosorbent assay (ELISA). Adiponectin significantly stimulated the production of VEGF, MMP-1 and MMP-13 in osteoblasts but not in endothelial cells, whereas it significantly stimulated the production of IL-6 and IL-8 in both endothelial cells and osteoblasts. The increase in VEGF production induced by adiponectin was significantly greater than that induced by IL-1beta. The production of IL-6 and IL-8 in adiponectin-stimulated endothelial cells was approximately 10-fold higher than that in IL-1beta-stimulated endothelial cells; in osteoblasts, adiponectin-induced IL-6 and IL-8 secretion was approximately twofold higher than that induced by IL-1beta. In addition, IL-8 production in endothelial cells was approximately sevenfold higher than in osteoblasts. However, IL-6 levels were similar between the two cell types, suggesting that adiponectin may be involved in the production of IL-8 in endothelial cells, which may have an important role in neutrophil recruitment to arthritic joints. Furthermore, the increases in protein expression induced by adiponectin were differentially regulated by hypoxia. In conclusion, adiponectin has a more important role than does IL-1beta in the production of mediators that drive synovitis and joint destruction in endothelial cells and osteoblasts at physiological concentrations.
Adiponectin/pharmacology/*physiology ; Arthritis, Rheumatoid/metabolism ; Cell Hypoxia ; Cell Line ; Human Umbilical Vein Endothelial Cells/drug effects/*metabolism ; Humans ; Interleukin-6/genetics/*metabolism ; Interleukin-8/genetics/*metabolism ; Matrix Metalloproteinase 1/genetics/*metabolism ; Osteoblasts/drug effects/*metabolism ; Vascular Endothelial Growth Factor A/genetics/*metabolism