RT Journal Article
T1 Disruption of GIP/GIPR axis in human adipose tissue is linked to obesity and insulin resistance.
A1 Ceperuelo-Mallafré, Victoria
A1 Durán, Xavier
A1 Pachón, Gisela
A1 Roche, Kelly
A1 Garrido-Sánchez, Lourdes
A1 Vilarrasa, Nuria
A1 Tinahones, Francisco J
A1 Vicente, Vicente
A1 Pujol, Jordi
A1 Vendrell, Joan
A1 Fernández-Veledo, Sonia
K1 Tejido adiposo
K1 Índice de masa corporal
K1 Línea celular
K1 Regulación hacia abajo
K1 Polipéptido inhibidor gástrico
K1 Resistencia a la insulina
K1 Obesidad
K1 Receptores de la hormona gastrointestinal
K1 Transducción de señal
K1 Circunferencia de la cintura
K1 Adipocitos
AB CONTEXTGlucose-dependent insulinotropic peptide (GIP) has a central role in glucose homeostasis through its amplification of insulin secretion; however, its physiological role in adipose tissue is unclear.OBJECTIVEOur objective was to define the function of GIP in human adipose tissue in relation to obesity and insulin resistance.DESIGNGIP receptor (GIPR) expression was analyzed in human sc adipose tissue (SAT) and visceral adipose (VAT) from lean and obese subjects in 3 independent cohorts. GIPR expression was associated with anthropometric and biochemical variables. GIP responsiveness on insulin sensitivity was analyzed in human adipocyte cell lines in normoxic and hypoxic environments as well as in adipose-derived stem cells obtained from lean and obese patients.RESULTSGIPR expression was downregulated in SAT from obese patients and correlated negatively with body mass index, waist circumference, systolic blood pressure, and glucose and triglyceride levels. Furthermore, homeostasis model assessment of insulin resistance, glucose, and G protein-coupled receptor kinase 2 (GRK2) emerged as variables strongly associated with GIPR expression in SAT. Glucose uptake studies and insulin signaling in human adipocytes revealed GIP as an insulin-sensitizer incretin. Immunoprecipitation experiments suggested that GIP promotes the interaction of GRK2 with GIPR and decreases the association of GRK2 to insulin receptor substrate 1. These effects of GIP observed under normoxia were lost in human fat cells cultured in hypoxia. In support of this, GIP increased insulin sensitivity in human adipose-derived stem cells from lean patients. GIP also induced GIPR expression, which was concomitant with a downregulation of the incretin-degrading enzyme dipeptidyl peptidase 4. None of the physiological effects of GIP were detected in human fat cells obtained from an obese environment with reduced levels of GIPR.CONCLUSIONSGIP/GIPR signaling is disrupted in insulin-resistant states, such as obesity, and normalizing this function might represent a potential therapy in the treatment of obesity-associated metabolic disorders.
PB Endocrine Society
SN 0021-972X
YR 2014
FD 2014-05
LK http://hdl.handle.net/10668/2050
UL http://hdl.handle.net/10668/2050
LA en
NO Ceperuelo-Mallafré V, Duran X, Pachón G, Roche K, Garrido-Sánchez L, Vilarrasa N, et al. Disruption of GIP/GIPR axis in human adipose tissue is linked to obesity and insulin resistance. J. Clin. Endocrinol. Metab.. 2014; 99(5):E908-19
NO Journal Article; Research Support, Non-U.S. Gov't;
DS RISalud
RD Apr 19, 2025