Glucose-dependent insulinotropic polypeptide enhances adipocyte development and glucose uptake in part through Akt activation.
OBJECTIVE
In addition to its role as the primary mediator of the enteroinsular axis, glucose-dependent insulinotropic polypeptide (GIP) may play a critical role in the development of obesity. The purpose of these studies was to characterize the effects of GIP and its receptor (GIPR) in adipocyte development and signaling.


METHODS
Effects of GIP and GIPR on differentiated 3T3-L1 cells were analyzed using Western blot analysis, Oil-Red-O staining, cyclic adenosine monophosphate radioimmunoassay, immunofluorescence microscopy, and glucose uptake measurements.


RESULTS
To determine whether GIP and GIPR are important components in adipocyte development, the expression profile of GIPR during differentiation was examined. GIPR protein expression was enhanced during the differentiation process, and coincubation with its ligand GIP augmented the expression of aP2, a fat cell marker. Conversely, the suppression of GIPR expression by a specific short hairpin RNA attenuated Oil-Red-O staining and aP2 expression, suggesting that the GIPR may play a critical role in adipocyte development. To investigate specific signaling components that may mediate the effects of GIP, we analyzed Akt, glucose transporter-4, and glucose uptake, all of which are modulated by insulin in fat cells. Like insulin, GIP induced the activation of Akt in a concentration-dependent manner, promoted membrane glucose transporter-4 accumulation, and enhanced [(3)H]-2-deoxyglucose uptake.


CONCLUSIONS
These studies provide further evidence for an important physiologic role for GIP in lipid homeostasis and possibly in the pathogenesis of obesity. Furthermore, our data indicate that the GIPR might represent a suitable target for the treatment of obesity.
Department of Medicine, Boston University School of Medicine and Boston Medical Center, Boston, Massachusetts, USA.
Diane H
DH
Song
Lisa
L
Getty-Kaushik
Eva
E
Tseng
Jonathan
J
Simon
Barbara E
BE
Corkey
M Michael
MM
Wolfe
D017667:Adipocytes / Q000502:physiology*; D002454:Cell Differentiation; D002478:Cells, Cultured; D005749:Gastric Inhibitory Polypeptide / Q000502:physiology*; D005947:Glucose / Q000378:metabolism*; D051275:Glucose Transporter Type 4 / Q000378:metabolism; D006801:Humans; D050417:Insulin-Secreting Cells / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D011964:Receptors, Gastrointestinal Hormone / Q000096:biosynthesis; D015398:Signal Transduction
D051275:Glucose Transporter Type 4; D011964:Receptors, Gastrointestinal Hormone; D005749:Gastric Inhibitory Polypeptide; C041086:gastric inhibitory polypeptide receptor; D051057:Proto-Oncogene Proteins c-akt; D005947:Glucose