Simplified model of insulin signaling.

Insulin binding to the extracellular domain of the insulin receptor elicits a conformational change, which in turn leads to receptor autophosphorylation (P) and tyrosine phosphorylation of intracellular protein substrates. Two main branching pathways are activated by insulin: (a) One is the MAPK signaling cascade, in which the Grb2/Sos pathway leads to activation of Ras signaling, affecting cell proliferation and apoptosis. In view of their mitogenic nature, these can be characterized as "growth signal" effects. (b) The other is the IRS pathway, which leads to activation of kinases dependent upon the heterodimeric (p85/p110) PI3K, such as Akt, also referred to as protein kinase B (PKB); Akt modulates enzyme activities that, besides affecting NO generation and apoptosis, control glucose, lipid, and protein metabolism. This PI3K-branching pathway is termed the "metabolic signal." PI(4, 5)P2, phosphoinositide 4,5 di-phosphate; PI(3, 4, 5)P3, phosphoinositide 3,4,5 tri-phosphate; PDK1 phosphoinositide–dependent kinase–1; MEK, MAPK kinase.

Venn diagram modeling the effect of the interaction between glucose toxicity and lack of insulin on the vulnerable state of critical illness. Complications of type 1 and type 2 diabetes are explained by hyperglycemia and/or lack of insulin effect. Critical illness is also characterized by hyperglycemia and lack of insulin effect, but additional risk factors render both of these effects more acutely toxic, as indicated by the blue shading. These risk factors include the post-hypoxia reperfused state, iNOS-activated NO generation, increased expression of GLUT-1 and GLUT-3 transporters, and cytokine-, neurological-, and hormone-induced alterations in cellular processes. Hence, improved outcome of critical illness with insulin-titrated maintenance of normoglycemia is likely to be explained by the prevention of both direct glucose toxicity and insulin-induced effects that are independent of glucose control.

Van den Berghe. J Clin Invest. 2004 Nov;114(9):1187-95.

 

Inflammation, stress, and diabetes

Metabolism and immunity are closely linked. Both overnutrition and undernutrition have implications for immune function. Starvation and malnutrition can suppress immune function and increase susceptibility to infections. Obesity is associated with a state of aberrant immune activity and increasing risk for associated inflammatory diseases, including atherosclerosis, diabetes, airway inflammation, and fatty liver disease. Thus, optimal nutritional and metabolic homeostasis is an important part of appropriate immune function and good health

Nutrient and pathogen sensing or response systems have important overlapping features, and their modulation by obesity or infection can lead to overlapping physiological outcomes. For example, the chronic inflammation of obesity leads to elevated plasma lipid levels and the development of insulin resistance, eventually resulting in fatty liver disease, atherosclerosis, and diabetes. Infection typically leads to a more transient and robust inflammatory response and short-term hyperlipidemia that aids in the resolution of the infection. In some circumstances of chronic infection, however, insulin resistance, diabetes, and atherosclerosis can result.

Wellen & Hotamisligil. J Clin Invest. 2005 May;115(5):1111-9.

 

Effect of salicylates on insulin signaling during insulin resistance.

(a) Normally, the occupied insulin receptor phosphorylates scaffold proteins, such as the IRS-1, on critical tyrosine residues. However, in insulin-resistant states, a number of agents, such as the cytokine TNF- or circulating FFAs, lead through intermediary signaling pathways to the activation of IKK, which in turn indirectly increases the number of phosphorylated serine and threonine residues (indicated by blue circles) on IRS-1. This modification blocks the tyrosine phosphorylation and converts IRS-1 into an insulin receptor inhibitory protein. (b) In the presence of salicylates, IKK activity is inhibited, reducing the IRS-1 serine/threonine phosphorylation and allowing IRS-1 to be phosphorylated on tyrosine. These phosphorylated tyrosine residues (black squares) serve as binding sites for a number of signaling molecules, most importantly PI 3'-kinase, which initiate signaling pathways regulating metabolism. Aspirin (ASA) also inhibits cyclooxygensases (COX) to prevent the generation of inflammatory prostaglandins (PGE) from arachidonic acid (AA) in a pathway unrelated to the effects of the drug on insulin action.

Birnbaum et al. J Clin Invest. 2001 Sep;108(5):655-9.

 

Proteins secreted by adipose tissue that are also thought to play a role in obesity-associated insulin resistance and diabetes.

Adipose-derived protein	Effect on insulin sensitivity	Other tissue sources
Leptin	Improvement	None
Adiponectin	Improvement	None
Adipsin / ASP	Decline	None
Resistin	Decline	None (rodent)
Resistin	Decline	macrophage (Human)
TNF-α	Decline	macrophage
IL-6	Decline	macrophage
MCP-1	Decline	macrophage
Visfatin	Improvement	Liver, lymphocytes
PAI-1	Decline	Liver
Angiotensinogen	Decline	Liver
Serum amyloid A	Not known	Liver
α1-acid glycoprotein	Not known	Liver

Lazar. Science. 2005 Jan 21;307(5708):373-5.

 

Plasma visfatin concentrations and fat depot-specific mRNA expression in humans

Visceral and subcutaneous adipose tissue display important metabolic differences that underlie the association of visceral obesity with obesity-related cardiovascular and metabolic alterations. Recently, visfatin was identified as an adipokine, which is predominantly secreted from visceral adipose tissue both in humans and mice. In this study, we examined whether visfatin plasma concentrations (using enzyme immunosorbent assay, Visfatin, C-terminal, (Human) EIA Kit, catalog No.: EK-003-80, Phoenix Pharmaceuticals, Belmont, USA) and mRNA expression (using RT-PCR) in visceral and subcutaneous fat correlates with anthropometric and metabolic parameters in 189 subjects with a wide range of obesity, body fat distribution, insulin sensitivity, and glucose tolerance. Visfatin plasma concentration correlates positively with the visceral visfatin mRNA expression (r2 = 0.17, P < 0.0001), BMI (r2 = 0.062, P = 0.004), percent body fat (r2 = 0.048, P = 0.01), and negatively with subcutaneous visfatin mRNA expression (r2 = 0.18, P < 0.0001). However, in a subgroup of 73 individuals, in which visceral fat mass was calculated from computed tomography scans, there was no correlation between plasma visfatin concentrations and visceral fat mass. We found no significant correlation between visfatin plasma concentrations and parameters of insulin sensitivity, including fasting insulin, fasting plasma glucose concentrations, and the glucose infusion rate during the steady state of an euglycemic-hyperinsulinemic clamp independent of percent body fat. Visfatin gene expression was not different between visceral and subcutaneous adipose tissue in the entire study group nor in selected subgroups. We found a significant correlation between visceral visfatin gene expression and BMI (r2 = 0.06, P = 0.001) and percent body fat (measured using dual-energy X-ray absorptiometry) (r2 = 0.044, P = 0.004), whereas no significant association between BMI or percent body fat and subcutaneous visfatin mRNA expression existed (both P >0.5). In conclusion, visfatin plasma concentrations and visceral visfatin mRNA expression correlated with measures of obesity but not with visceral fat mass or waist-to-hip ratio. In addition, we did not find differences in visfatin mRNA expression between visceral and subcutaneous adipose tissue in humans.

Correlation between plasma visfatin concentrations and % body fat in men (A) and women (B). Data were log transformed to achieve normal distribution.

Correlation between plasma visfatin concentration and visfatin mRNA expression in visceral (A) or subcutaneous (B) fat depots (n = 163). Data were log transformed to achieve normal distribution.

Correlation between plasma visfatin concentration, fasting plasma insulin concentrations (A), and fasting plasma glucose concentrations (B) (n = 163). Data were log transformed to achieve normal distribution.

Berndt et al. Diabetes. 2005 Oct;54(10):2911-6.

 

Increased plasma visfatin concentrations in morbidly obese subjects are reduced after gastric banding

CONTEXT: The insulin-mimetic adipocytokine visfatin has been linked to obesity. The influence of weight loss on plasma visfatin concentrations in obese subjects is unknown yet.
OBJECTIVES: In this study we investigated whether plasma visfatin concentrations are altered by weight loss in patients with obesity.
DESIGN AND PATIENTS: In a prospective study, fasting plasma visfatin, leptin, and adiponectin concentrations were measured before and 6 months after gastric banding in 31 morbidly obese patients aged 40 +/- 11 yr with a body mass index (BMI) of 46 +/- 5 kg/m(2). Fourteen healthy subjects aged 29 +/- 5 yr with a BMI less than 25 kg/m(2) served as controls.
RESULTS: Visfatin plasma concentrations were markedly elevated in obese subjects (0.037 +/- 0.008 microg/ml), compared with controls (0.001 +/- 0.000 microg/ml, P < 0.001). Gastric banding reduced BMI to 40 +/- 5 kg/m(2), visfatin to 19.2 +/- 10.9 ng/ml, and leptin from 39.0 +/- 12.4 to 29.7 +/- 10.0 ng/ml and increased adiponectin from 0.015 +/- 0.007 to 0.017 +/- 0.007 microg/ml (all P < 0.05) after 6 months. Insulin sensitivity as estimated by the homeostasis model assessment insulin resistance index was unchanged from 5.8 +/- 3.1 to 4.6 +/- 1.9 (P = 0.13), but individual changes of insulin resistance and visfatin were significantly associated (P < 0.05, r = -0.43).
CONCLUSIONS: Elevated plasma visfatin concentrations in morbidly obese subjects are reduced after weight loss. This may be related to changes in insulin resistance over time.

Haider et al. J Clin Endocrinol Metab. 2006 Apr;91(4):1578-81.

 

Increased visfatin concentrations in women with gestational diabetes mellitus.

The recently discovered adipocytokine visfatin has insulin-like properties. It lowers blood glucose and improves insulin sensitivity; however, clinical data on visfatin are limited. To evaluate the role of visfatin in GDM (gestational diabetes mellitus), we determined visfatin levels in women with GDM and in healthy pregnant controls. Furthermore, visfatin concentrations were investigated longitudinally during pregnancy and after delivery in a subgroup of women with GDM. Blood for measurement of visfatin and metabolic parameters was obtained from 64 women with GDM [median week of gestation, 34 (interquartile range, 27-36) weeks] and 30 healthy pregnant controls [median week of gestation, 34 (interquartile range, 28-36) weeks]. In a subgroup of 24 women with GDM, visfatin, leptin and metabolic parameters were investigated twice during pregnancy (28-30 and 38-40 weeks of gestation) and 2 weeks after delivery. In the cross-sectional analysis, median visfatin levels were significantly elevated in women with GDM [64.0 (interquartile range, 50.9-74.8) ng/ml] compared with controls [46.0 (interquartile range, 36.9-54.6) ng/ml; P<0.0001]. In women with GDM, visfatin correlated with week of gestation at the time of blood draw (R=0.35, P=0.005). No association with fasting glucose, insulin, homoeostasis model assessment-insulin resistance or body mass index was observed. According to the longitudinal analysis, visfatin increased during pregnancy (P=0.002) and rose further after delivery (P=0.014), whereas leptin and insulin levels decreased after parturition (both P<0.001). In conclusion, visfatin is elevated in women with GDM and increases during the course of pregnancy as well as after delivery. Furthermore, visfatin shows no association with insulin and leptin in women with GDM.

Krzyzanowska et al. Clin Sci (Lond). 2006 May;110(5):605-9

 

Plasma visfatin levels in patients with newly diagnosed and untreated type 2 diabetes mellitus and impaired glucose tolerance.

Visfatin, a new adipokine, facilitates adipogenesis and has insulin-mimetic properties. We aimed to investigate the plasma visfatin levels in patients with newly diagnosed and untreated type 2 diabetes mellitus (T2DM) and impaired glucose tolerance (IGT), who had no obesity or hypertension. Twenty-two patients with T2DM, 18 subjects with IGT and 40 healthy controls were enrolled. Visfatin levels were measured along with the BMI, blood pressure, lipids, glucose, insulin, adiponectin and hsCRP levels, and HOMA-IR indexes. Age, sex and BMI were similar in all groups. Visfatin levels were higher in the diabetic group than the controls (p=0.01). There was no significant difference in the visfatin levels between the T2DM and IGT groups as well as IGT group and healthy controls. Plasma visfatin concentrations did not differ between men and women. Visfatin levels did not correlate with BMI, blood pressure, plasma adiponectin, insulin, hsCRP, glucose and lipid levels or HOMA-IR indexes in the three groups. These results indicate that hyperglycemia causes an increase in plasma visfatin levels and, as in people with T2DM but not with IGT, this increase gets more prominent as the glucose intolerance worsens.

Dogru et al. Diabetes Res Clin Pract. 2007 Apr;76(1):24-9.

 

Elevated Plasma Level of Visfatin/Pre-B Cell Colony-Enhancing Factor in Patients with Type 2 Diabetes Mellitus

CONTEXT: Visfatin (also known as pre-B cell colony-enhancing factor or PBEF) is a cytokine that highly expressed in visceral fat and whose blood levels correlate with obesity. Originally isolated as a secreted factor that promote the growth of B cell precursors and recently found to act as an insulin analogue on the insulin receptor, its pathophysiologic role in humans remain largely unknown.
OBJECTIVES: In this study we investigate whether or not plasma visfatin level is altered in patients with type 2 diabetes mellitus (T2DM).
DESIGN AND PATIENTS: Plasma visfatin as well as adiponectin and resistin concentrations were measured through ELISA in type 2 diabetic and non-diabetic subjects.
RESULTS: A total of 61 patients with T2DM and 59 sex- and age-matched non-diabetic subjects were studied. Plasma visfatin was found to be elevated in patients with T2DM (31.9 ± 31.7 ng/mL vs. 15.8 ± 16.7 ng/mL, p= 0.002). In contrast, adiponectin was decreased (4.3 ± 2.5 μg/mL vs. 30.8 ± 10.3 μg/mL, p< 0.001), while plasma resistin level did not differ between the groups. Increasing concentrations of visfatin were independently and significantly associated with T2DM. Multiple logistic regression analysis revealed visfatin as an independent association factor for T2DM even after full adjustment of known biomarkers. The association between adiponectin and T2DM was no longer significant after adjustments for BMI or WHR. In a multiple linear regression analysis, only WHR was independently associated with plasma visfatin level.
CONCLUSION: Our results indicate that visfatin may play a role in the pathogenesis of T2DM.

Chen et al. J Clin Endocrinol Metab. 2006 Jan;91(1):295-9.

 

Visfatin is an adipokine but it is not regulated by thiazolidinediones

CONTEXT: Visfatin was recently reported to be expressed in human adipose tissue and to exert insulin-mimicking effects. Objective: To examine if visfatin is a true adipokine and expressed in isolated fat cells. We also examined if visfatin is regulated by thiazolidinediones and, thus, can contribute to the ability of these agents to improve insulin sensitivity.
DESIGN: Open labeled drug therapy trial.
SETTING: University Hospital.
PATIENTS: Seven newly diagnosed and previously untreated Type 2 diabetic patients and 6 healthy individuals with reduced insulin sensitivity participated in the study.
INTERVENTION: Pioglitazone therapy, 30-45 mg per day for 3-4 weeks.
MAIN OUTCOME MEASURES: Serum and adipose tissue mRNA levels of visfatin and adiponectin.
RESULTS: Visfatin mRNA is expressed in both adipose tissue and isolated adipocytes. Treatment with thiazolidinediones for 3-4 weeks did not alter the gene expression or circulating levels of visfatin in either the non-diabetic or the diabetic individuals, while adiponectin increased significantly.
CONCLUSION: The present study shows that visfatin is a true adipokine but it is not regulated by TZD and, thus, is unlikely to contribute to the insulin-sensitizing actions of these drugs.

Hammarstedt et al. J Clin Endocrinol Metab. 2006 Mar;91(3):1181-4.

 

Genetic Variation in the Visfatin Gene (PBEF1) and its Relation to Glucose Metabolism and Fat Depot Specific mRNA Expression in Humans.

CONTEXT AND OBJECTIVE: Visfatin is a peptide suggested to play a role in glucose homeostasis. In the present study we investigated the role of genetic variation in the visfatin gene in the pathophysiology of obesity/type 2 diabetes mellitus (T2DM).
DESIGN: The visfatin gene (PBEF1) was sequenced in DNA samples from 24 non-related Caucasian subjects. Identified genetic variants were used for association analyses of T2DM in a case-control study (503 diabetic subjects and 476 healthy controls) and T2DM-related traits in 626 non-diabetic subjects. Effect of genetic variation in the visfatin gene on its mRNA expression in a subgroup of 157 non-diabetic subjects with measurements of visfatin mRNA expression in visceral and sc fat depots was also analyzed.
RESULTS: Seven single nucleotide polymorphisms (SNPs) and one insertion/deletion were identified. Three SNPs (rs9770242, -948G>T, rs4730153) which were representatives of their linkage disequilibrium groups were genotyped in Caucasians from Germany with a wide range of body fat distribution and insulin sensitivity for association analyses. No association of T2DM with any of the genotyped SNPs or their haplotypes was found. However, the ratio of visceral/sc visfatin mRNA expression was associated with all 3 genetic polymorphisms (P < 0.05). Moreover, the -948G>T variant was associated with 2 h plasma glucose and fasting insulin concentrations (P < 0.05) in non-diabetic subjects.
CONCLUSIONS: In conclusion, our data suggest that genetic variation in the visfatin gene may have a minor effect on visceral and sc visfatin mRNA expression profiles but does not play a major role in the development of obesity or T2DM.

Böttcher et al. J Clin Endocrinol Metab. 2006 Jul;91(7):2725-31.

Mapping in Human Visceral White fat tissue, Rat & Mouse Liver tissue (H-003-84 / G-003-84)

 

 

 

Tissue Sample	Human visceral white fat tissue, rat & mouse liver tissue
Fixative	10% formalin
Embedding	Paraffin
Negative Control	No primary antibody (pre-immuno serum)
Pretreatment	Intact
Blocking	2% Normal Goat Serum
Primary Antibody	Rabbit Anti-Visfatin (400-450) (Human) Antiserum (Catalog No.:H-003-84)
Optimal Dilution	1:200~500, 1 hour at RT
Secondary Antibody	Goat Anti-Rabbit IgG, Biotinylated (1:400), 30 min
Amplification	ABC (Vector) (1:400, 30 min)
Detection System	HRP
Substrate	DAB (Sigma), 3 min
Counterstained	Hematoxylin, 30 sec

Mapping in Rat Liver tissue (H-003-82)

 

Tissue Sample	Rat liver tissue
Fixative	10% formalin
Embedding	Paraffin
Negative Control	No primary antibody (pre-immuno serum)
Pretreatment	Intact
Blocking	2% Normal Goat Serum
Primary Antibody	Rabbit Anti-Visfatin (412-431) (Human) Antiserum (Catalog No.:H-003-82)
Optimal Dilution	1:200~500, 1 hour at RT
Secondary Antibody	Goat Anti-Rabbit IgG, Biotinylated (1:400), 30 min
Amplification	ABC (Vector) (1:400, 30 min)
Detection System	HRP
Substrate	DAB (Sigma), 3 min
Counterstained	Hematoxylin, 30 sec

Mapping in Mouse & Rat Liver tissue (H-003-93)

 

 

Tissue Sample	Mouse & Rat Liver
Fixative	10% formalin
Embedding	Paraffin
Negative Control	No primary antibody (pre-immuno serum)
Pretreatment	Intact
Blocking	2% Normal Goat Serum
Primary Antibody	Rabbit Anti-Visfatin (397-422) (Human) Antiserum (Catalog No.:H-003-93)
Optimal Dilution	1:200, 1 hour at RT
Secondary Antibody	Goat Anti-Rabbit IgG, Biotinylated (1:400), 30 min
Amplification	ABC (Vector) (1:400, 30 min)
Detection System	HRP
Substrate	DAB (Sigma), 3 min
Counterstained	Hematoxylin, 30 sec

Mapping in Rat Liver tissue (H-003-79)

 

Western Blot Analysis by Visfatin (412-431) (Human) Antibody (H-003-82)

Western Blot Analysis by Visfatin (412-431) (Human) Purified IgG (G-003-82)

Visfatin Normal Human Plasma Protein/Peptide Levels

Visfatin (obese subjects)	37 ± 1 ng/ml	Haider et al. J Clin Endocrinol Metab, 2006, 91(4): 1578-1581
Visfatin C-terminal (Non-extracted EDTA plasma)	19.1~38.67 ng/ml	Phoenix Pharmaceuticals

Phoenix's Visfatin C-Terminal (Human) EIA Kit confirmed lower levels of blood PBEF/Visfatin in Heterozygous PBEF/Visfatin knock out mice (EK-003-80)

 

Linearity data from Phoenix for EK-003-80:

Sample	Dilution	Observed (ng/ml)	Expected (ng/ml)	[Observed/Expected] x 100 (%)
Non-extracted EDTA plasma from subjects (n=6)	neat	38.67
	1/2	17.15	34.3	88.7
	1/4	8.66	34.64	89.5
	1/8	6.17	49.36	127.6
	1/16	3.36	53.76	139.0
Non-extracted EDTA plasma from subjects (n=4)	neat	19.1
	1/2	10.8	9.55	113.1
	1/4	4.9	4.78	102.1
	1/8	1.9	2.38	79.8
Non-extracted EDTA plasma from mouse (n=6)	neat	52.1
	1/2	28.4	26.05	109.0
	1/4	14.5	13.02	111.4
	1/8	7.2	6.51	110.6
	1/16	4.2	3.26	128.8
	1/32	2.05	1.63	125.8

 

Western Blot Analysis by Visfatin Western Blot Kit in Mouse Fat Tissue (WBK-003-81)

Amino Acid Sequence of Visfatin (Human)

 

Links to publications that use EK-003-80:

Wang et al. Perivascular adipose tissue-derived visfatin is a vascular smooth muscle cell growth factor: role of nicotinamide mononucleotide.
Cardiovasc Res. 2009 Feb 1;81(2):370-80.

Skokowa et al. NAMPT is essential for the G-CSF-induced myeloid differentiation via a NAD(+)-sirtuin-1-dependent pathway.
Nat Med. 2009 Feb;15(2):151-8.

de Boer et al. Plasma levels of PBEF/Nampt/visfatin are decreased in patients with liver cirrhosis.
Am J Physiol Gastrointest Liver Physiol. 2009 Feb;296(2):G196-201.

du Luis et al. Relation of visfatin to cardiovascular risk factors and adipocytokines in patients with impaired fasting glucose.
Nutrition. 2009 Jan 6. [Epub ahead of print]

Li et al. The adipose triglyceride lipase, adiponectin and visfatin are downregulated by tumor necrosis factor-alpha (TNF-alpha) in vivo.
Cytokine. 2009 Jan;45(1):12-9.

Kato et al. Relationship between serum pre-B cell colony-enhancing factor/visfatin and atherosclerotic parameters in chronic hemodialysis patients.
Am J Nephrol. 2009;29(1):31-5.

Zhong et al. Increased serum visfatin in patients with metabolic syndrome and carotid atherosclerosis.
Clin Endocrinol (Oxf). 2008 Dec;69(6):878-84.

Retnakaran et al. Correlation of circulating full-length visfatin (PBEF/NAMPT) with metabolic parameters in subjects with and without diabetes: a cross-sectional study.
Clin Endocrinol (Oxf). 2008 Dec;69(6):885-93.

Younossi et al. A novel diagnostic biomarker panel for obesity-related nonalcoholic steatohepatitis (NASH).
Obes Surg. 2008 Nov;18(11):1430-7.

Storka et al. Angiotensin inhibition stimulates PPARgamma and the release of visfatin.
Eur J Clin Invest. 2008 Nov;38(11):820-6.

Panidis et al. Plasma visfatin levels in normal weight women with polycystic ovary syndrome.
Eur J Intern Med. 2008 Oct;19(6):406-12.

Dahmen et al. Elevated peripheral visfatin levels in narcoleptic patients.
PLoS ONE. 2008 Aug 20;3(8):e2980.

Botella-Carretero et al. The increase in serum visfatin after bariatric surgery in morbidly obese women is modulated by weight loss, waist circumference, and presence or absence of diabetes before surgery.
Obes Surg. 2008 Aug;18(8):1000-6.

Brema et al. Plasma visfatin is reduced after aerobic exercise in early onset type 2 diabetes mellitus.
Diabetes Obes Metab. 2008 Jul;10(7):600-2.

Palin et al. Visfatin expression is not associated with adipose tissue abundance in the porcine model.
Domest Anim Endocrinol. 2008 Jul;35(1):58-73.

Ibáñez et al. Gender specificity of body adiposity and circulating adiponectin, visfatin, insulin, and insulin growth factor-I at term birth: relation to prenatal growth.
J Clin Endocrinol Metab. 2008 Jul;93(7):2774-8.

Perez-Iglesias et al. Effect of antipsychotics on peptides involved in energy balance in drug-naive psychotic patients after 1 year of treatment.
J Clin Psychopharmacol. 2008 Jun;28(3):289-95.

de Luis et al. Effect of a hypocaloric diet on serum visfatin in obese non-diabetic patients.
Nutrition. 2008 Jun;24(6):517-21.

Ibáñez et al. Visceral adiposity without overweight in children born small for gestational age.
J Clin Endocrinol Metab. 2008 Jun;93(6):2079-83.

Yilmaz et al. Endothelial dysfunction in type-2 diabetics with early diabetic nephropathy is associated with low circulating adiponectin.
Nephrol Dial Transplant. 2008 May;23(5):1621-7.

Bouhours-Nouet et al. High birth weight and early postnatal weight gain protect obese children and adolescents from truncal adiposity and insulin resistance: metabolically healthy but obese subjects?
Diabetes Care. 2008 May;31(5):1031-6.

Krzysik-Walker et al. Is visfatin an adipokine or myokine? Evidence for greater visfatin expression in skeletal muscle than visceral fat in chickens.
Endocrinology. 2008 Apr;149(4):1543-50.

Matsui et al. Visfatin (pre-B cell colony-enhancing factor) gene expression in patients with rheumatoid arthritis.
Ann Rheum Dis. 2008 Apr;67(4):571-2.

Jarrar et al. Adipokines and cytokines in non-alcoholic fatty liver disease.
Aliment Pharmacol Ther. 2008 Mar 1;27(5):412-21.

Yilmaz et al. Serum visfatin concentration and endothelial dysfunction in chronic kidney disease.
Nephrol Dial Transplant. 2008 Mar;23(3):959-65.

Kendal-Wright et al. Chronic stretching of amniotic epithelial cells increases pre-B cell colony-enhancing factor (PBEF/visfatin) expression and protects them from apoptosis.
Placenta. 2008 Mar;29(3):255-65.

Rauchenzauner et al. Adiponectin and visfatin concentrations in children treated with valproic acid.
Epilepsia. 2008 Feb;49(2):353-7.

Choi et al. Implication of lipocalin-2 and visfatin levels in patients with coronary heart disease.
Eur J Endocrinol. 2008 Feb;158(2):203-7.

Peng et al. Relationships between serum adiponectin, leptin, resistin, visfatin levels and bone mineral density, and bone biochemical markers in Chinese men.
Clin Chim Acta. 2008 Jan;387(1-2):31-5.

Kostapanos et al. Effect of rosuvastatin treatment on plasma visfatin levels in patients with primary hyperlipidemia.
Eur J Pharmacol. 2008 Jan 14;578(2-3):249-52.

Filippatos et al. Increased plasma visfatin levels in subjects with the metabolic syndrome.
Eur J Clin Invest. 2008 Jan;38(1):71-2.

López-Bermejo et al. Cord serum visfatin at term birth: maternal smoking unmasks the relation to foetal growth.
Clin Endocrinol (Oxf). 2008 Jan;68(1):77-81.

Seo et al. Plasma visfatin levels are positively associated with circulating interleukin-6 in apparently healthy Korean women.
Diabetes Res Clin Pract. 2008 Jan;79(1):108-11.

Mazaki-Tovi et al. Visfatin/Pre-B cell colony-enhancing factor in amniotic fluid in normal pregnancy, spontaneous labor at term, preterm labor and prelabor rupture of membranes: an association with subclinical intrauterine infection in preterm parturition.
J Perinat Med. 2008;36(6):485-96.

Goldfine et al. Patients with neuroglycopenia after gastric bypass surgery have exaggerated incretin and insulin secretory responses to a mixed meal.
J Clin Endocrinol Metab. 2007 Dec;92(12):4678-85.

Körner et al. Molecular characteristics of serum visfatin and differential detection by immunoassays.
J Clin Endocrinol Metab. 2007 Dec;92(12):4783-91.

Shea et al. Serum retinol-binding protein 4 concentrations in response to short-term overfeeding in normal-weight, overweight, and obese men.
Am J Clin Nutr. 2007 Nov;86(5):1310-5.

Oki et al. Circulating visfatin level is correlated with inflammation, but not with insulin resistance.
Clin Endocrinol (Oxf). 2007 Nov;67(5):796-800.

Garcia-Fuentes et al. Plasma Visfatin Concentrations in Severely Obese Subjects Are Increased After Intestinal Bypass
Obesity (Silver Spring). 2007 Oct;15(10):2391-5.

Choi et al. Effect of exercise training on plasma visfatin and eotaxin levels.
Eur J Endocrinol. 2007 Oct;157(4):437-42.

Wang et al. The circulating PBEF/NAMPT/visfatin level is associated with a beneficial blood lipid profile.
Pflugers Arch. 2007 Sep;454(6):971-6.

Chen et al. The relationship between visfatin levels and anthropometric and metabolic parameters: association with cholesterol levels in women
Metabolism. 2007 Sep;56(9):1216-20.

Brentano et al. Pre-B cell colony-enhancing factor/visfatin, a new marker of inflammation in rheumatoid arthritis with proinflammatory and matrix-degrading activities.
Arthritis Rheum. 2007 Sep;56(9):2829-39.

Zahorska-Markiewicz et al. Serum concentration of visfatin in obese women.
Metabolism. 2007 Aug;56(8):1131-4.

Hsieh et al. Both slow-release and regular-form metformin improve glycemic control without altering plasma visfatin level in patients with type 2 diabetes mellitus.
Metabolism. 2007 Aug;56(8):1087-92.

Nüsken et al. Preanalytical influences on the measurement of visfatin by enzyme immuno assay.
Clin Chim Acta. 2007 Jul;382(1-2):154-6.

Haider et al. Visfatin response to glucose is reduced in women with gestational diabetes mellitus.
Diabetes Care. 2007 Jul;30(7):1889-91.

Malamitsi-Puchner et al. Perinatal circulating visfatin levels in intrauterine growth restriction.
Pediatrics. 2007 Jun;119(6):e1314-8.

Zhou et al. Tigogenin inhibits adipocytic differentiation and induces osteoblastic differentiation in mouse bone marrow stromal cells.
Mol Cell Endocrinol. 2007 May 30;270(1-2):17-22.

Ingelsson et al. Clinical correlates of circulating visfatin levels in a community-based sample.
Diabetes Care. 2007 May;30(5):1278-80.

Lewandowski et al. Elevated serum levels of visfatin in gestational diabetes: a comparative study across various degrees of glucose tolerance.
Diabetologia. 2007 May;50(5):1033-7.

Haider et al. Effect of rosiglitazone on visfatin and retinol-binding protein-4 plasma concentrations in HIV-positive patients.
Clin Pharmacol Ther. 2007 Apr;81(4):580-5.

Malamitsi-Puchner et al. Blood visfatin concentrations in normal full-term pregnancies.
Acta Paediatr. 2007 Apr;96(4):526-9.

Sandeep et al. Serum visfatin in relation to visceral fat, obesity, and type 2 diabetes mellitus in Asian Indians.
Metabolism. 2007 Apr;56(4):565-70.

Takebayashi et al. Association between plasma visfatin and vascular endothelial function in patients with type 2 diabetes mellitus.
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Dogru et al. Plasma visfatin levels in patients with newly diagnosed and untreated type 2 diabetes mellitus and impaired glucose tolerance.
Diabetes Res Clin Pract. 2007 Apr;76(1):24-9.

Fernández-Real et al. Circulating visfatin is associated with parameters of iron metabolism in subjects with altered glucose tolerance.
Diabetes Care. 2007 Mar;30(3):616-21.

Dogru et al. Plasma visfatin levels in young male patients with uncomplicated and newly diagnosed hypertension.
J Hum Hypertens. 2007 Feb;21(2):173-5.

Zhou et al. Macrostemonoside A promotes visfatin expression in 3T3-L1 cells.
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Manco et al. Effect of massive weight loss on inflammatory adipocytokines and the innate immune system in morbidly obese women.
J Clin Endocrinol Metab. 2007 Feb;92(2):483-90.

Dahl et al. Increased expression of visfatin in macrophages of human unstable carotid and coronary atherosclerosis: possible role in inflammation and plaque destabilization.
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Sun et al. Serum visfatin concentrations are positively correlated with serum triacylglycerols and down-regulated by overfeeding in healthy young men.
Am J Clin Nutr. 2007 Feb;85(2):399-404.

Varma et al. Human visfatin expression: relationship to insulin sensitivity, intramyocellular lipids, and inflammation.
J Clin Endocrinol Metab. 2007 Feb;92(2):666-72.

Moschen et al. Visfatin, an adipocytokine with proinflammatory and immunomodulating properties.
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Frydelund-Larsen et al. Visfatin mRNA expression in human subcutaneous adipose tissue is regulated by exercise.
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Yonezawa et al. Visfatin is present in bovine mammary epithelial cells, lactating mammary gland and milk, and its expression is regulated by cAMP pathway.
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Dimitriadis et al. Insulin action in adipose tissue and muscle in hypothyroidism.
J Clin Endocrinol Metab. 2006 Dec;91(12):4930-7.

Tan et al. Increased visfatin messenger ribonucleic acid and protein levels in adipose tissue and adipocytes in women with polycystic ovary syndrome: parallel increase in plasma visfatin.
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Krzyzanowska et al. Increase in visfatin after weight loss induced by gastroplastic surgery.
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Haider et al. Exercise training lowers plasma visfatin concentrations in patients with type 1 diabetes.
J Clin Endocrinol Metab. 2006 Nov;91(11):4702-4.

Haider et al. Free fatty acids normalize a rosiglitazone-induced visfatin release.
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López-Bermejo et al. Serum visfatin increases with progressive beta-cell deterioration.
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Haider et al. The adipokine visfatin is markedly elevated in obese children.
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Otero et al. Changes in plasma levels of fat-derived hormones adiponectin, leptin, resistin and visfatin in patients with rheumatoid arthritis.
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Jian et al. The visfatin gene is associated with glucose and lipid metabolism in a Chinese population.
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Schindler et al. Impact of antiretroviral therapy on visfatin and retinol-binding protein 4 in HIV-infected subjects.
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Haider et al. The release of the adipocytokine visfatin is regulated by glucose and insulin.
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Pagano et al. Reduced plasma visfatin/pre-B cell colony-enhancing factor in obesity is not related to insulin resistance in humans.
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Nowell et al. Regulation of pre-B cell colony-enhancing factor by STAT-3-dependent interleukin-6 trans-signaling: implications in the pathogenesis of rheumatoid arthritis.
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Böttcher et al. Genetic variation in the visfatin gene (PBEF1) and its relation to glucose metabolism and fat-depot-specific messenger ribonucleic acid expression in humans.
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Krzyzanowska et al. Increased visfatin concentrations in women with gestational diabetes mellitus.
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Haider et al. Increased plasma visfatin concentrations in morbidly obese subjects are reduced after gastric banding.
J Clin Endocrinol Metab. 2006 Apr;91(4):1578-81.

Curat et al. Macrophages in human visceral adipose tissue: increased accumulation in obesity and a source of resistin and visfatin.
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Hammarstedt et al. Visfatin is an adipokine, but it is not regulated by thiazolidinediones.
J Clin Endocrinol Metab. 2006 Mar;91(3):1181-4.

Chen et al. Elevated plasma level of visfatin/pre-B cell colony-enhancing factor in patients with type 2 diabetes mellitus.
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Berndt et al. Plasma visfatin concentrations and fat depot-specific mRNA expression in humans.
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Chan et al. Adiponectin and other adipocytokines as predictors of markers of triglyceride-rich lipoprotein metabolism.
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