Abstract 1216: The Cardioactive Peptide Apelin Increases Adipocyte Glucose Uptake and is Necessary for the Maintenance of Systemic Insulin Sensitivity
Background: Apelin, a peptide hormone with unique cardioactive properties, is also an adipokine, secreted by adipocytes in response to insulin. However, the overall effect of apelin on insulin sensitivity remains largely uncharacterized.
Methods: For in vitro experiments, 3T3L1 cells were differentiated into adipocytes over 8 days, with apelin (1 microM) added daily to the media. Cells were then treated with insulin (100 nM; n = 5) for 30 minutes and incubated with 2-[3H]-deoxyglucose. Glucose incorporation was then measured by scintillation counting. For in vivo experiments (n = 4 all studies), apelin-deficient (KO) mice were created by homologous recombination in embryonic stem cells. At age 7 weeks, insulin and glucose tolerance tests, as well as an enzyme immunosorbent assay for insulin, were performed after a 6-hour fast. The mice were then scanned by computed tomography using a GE eXplore RS MicroCT system, and visceral adipose content was determined with MicroView software. Upon sacrifice 1 week later, visceral adipocytes were isolated via collagenase digestion, exposed to insulin, and assessed for glucose uptake as above.
Results: Because apelin is upregulated by insulin in adipocytes, we measured glucose uptake in differentiated 3T3L1 cells chronically dosed with apelin. Though no differences were observed in basal uptake, insulin-induced uptake was increased versus control (p < 0.05). To further investigate the role of apelin in vivo, we assessed for insulin resistance in apelin KO mice. At 8 weeks of age, apelin KOs were heavier than age-matched wild type controls (25 vs. 22 g; p < 0.05). Though fasting glucose levels were not significantly different between groups, insulin levels were increased in the KOs (895 vs. 477 pg/microL; p < 0.05). In addition, both insulin and glucose tolerance tests were significantly abnormal in the KOs compared to wild type. Moreover, visceral fat volume was greater in the KOs (274 vs. 248 mm3/g body weight; p < 0.05). Finally, insulin-stimulated uptake was reduced (p < 0.05).
Conclusions: Apelin is necessary for the proper maintenance of glucose homeostasis. Furthermore, apelin potentiates insulin-induced glucose uptake in adipocytes, suggesting a possible mechanism for its insulin sensitizing effects.