Sie befinden Sich nicht im Netzwerk der Universität Paderborn. Der Zugriff auf elektronische Ressourcen ist gegebenenfalls nur via VPN oder Shibboleth (DFN-AAI) möglich. mehr Informationen...
Regulation of Resistin Expression and Circulating Levels in Obesity, Diabetes, and Fasting
Ist Teil von
Diabetes (New York, N.Y.), 2004-07, Vol.53 (7), p.1671-1679
Ort / Verlag
Alexandria, VA: American Diabetes Association
Erscheinungsjahr
2004
Link zum Volltext
Quelle
MEDLINE
Beschreibungen/Notizen
Regulation of Resistin Expression and Circulating Levels in Obesity, Diabetes, and Fasting
Michael W. Rajala 1 ,
Yong Qi 2 ,
Hiral R. Patel 2 ,
Nobuhiko Takahashi 2 ,
Ronadip Banerjee 2 ,
Utpal B. Pajvani 1 ,
Madhur K. Sinha 3 ,
Ronald L. Gingerich 3 ,
Philipp E. Scherer 1 and
Rexford S. Ahima 2
1 Department of Cell Biology and Diabetes Research and Training Center, Albert Einstein College of Medicine, Bronx, New York
2 Department of Medicine, Division of Endocrinology, Diabetes and Metabolism, University of Pennsylvania, Philadelphia, Pennsylvania
3 Linco Research, St. Charles, Missouri
Address correspondence and reprint requests to Rexford S. Ahima, MD, PhD, University of Pennsylvania School of Medicine, Division
of Endocrinology, Diabetes and Metabolism, 764 Clinical Research Building, 415 Curie Blvd., Philadelphia, PA 19104. E-mail:
ahima{at}mail.med.upenn.edu
Abstract
Resistin was originally reported as an adipose tissue–specific hormone that provided a link between obesity and diabetes.
Resistin protein level was elevated in obese mice and decreased by insulin-sensitizing thiazolidinediones. Immunoneutralization
of resistin improved insulin sensitivity in diet-induced obese mice, while the administration of exogenous resistin induced
insulin resistance. More recently, we have shown that ablation of the resistin gene in mice decreased fasting glucose through
impairment of gluconeogenesis, while resistin treatment in these knockout mice increased hepatic glucose production. However,
the link between resistin and glucose homeostasis has been questioned by studies demonstrating reduced, rather than increased,
resistin mRNA expression in obese and diabetic mice. To better understand the regulation of resistin, we developed a sensitive
and specific RIA resistin that could accurately measure serum resistin levels in several mouse models. We show that while
resistin mRNA is indeed suppressed in obese mice, the circulating resistin level is significantly elevated and positively
correlated with insulin, glucose, and lipids. Both resistin mRNA expression and protein levels in Lep ob/ob mice are suppressed by leptin treatment in parallel with reductions in glucose and insulin. In wild-type mice, serum resistin
increases after nocturnal feeding, concordant with rising levels of insulin. Resistin mRNA and protein levels decline in parallel
with glucose and insulin during fasting and are restored after refeeding. We performed clamp studies to determine whether
resistin is causally related to insulin and glucose. Adipose resistin expression and serum resistin increased in response
to hyperinsulinemia and further in response to hyperglycemia. Taken together, these findings suggest that the nutritional
regulation of resistin and changes in resistin gene expression and circulating levels in obesity are mediated, at least in
part, through insulin and glucose.
DEXA, dual-energy X-ray absorptiometry
ELISA, enzyme-linked immunosorbent assay
RIA, radioimmunoassay
TBS, Tris-buffered saline
TZD, thiazolidinedione
Footnotes
Accepted March 31, 2004.
Received October 20, 2003.
DIABETES