Glucose-dependent insulinotropic polypeptide (GIP) is an incretin hormone secreted by K-cells of proximal small intestine that is secreted postprandial in response to glucose and fat ingestion. Its effect is mediated through a GIP receptor (GIPR) which is widely expressed in different tissues, e.g. pancreatic islets, adipose tissue, skeletal muscle, adrenal cortex, heart, pituitary and in some regions of the brain. However, only the effect of GIP in pancreatic beta-cells is well-established where GIP stimulates glucose-induced insulin response. The purpose of our studies was to analyze effects of GIP on glucose uptake in differentiated 3T3-L1 cells (murine adipocytes) and RD18 cells (human skeletal muscle). Therefore, cells were incubated with either GIP or insulin or a combination of both.
Glucose-uptake of cells was determined with [3H]-2-deoxyglucose-assay. In 3T3-L1 cells as well as RD18 cells GIP slightly increased glucose uptake (118.2±12.1% (3T3-L1); 112.3±6.1% (RD18)). In combination with insulin we observed no additive effects in RD18 cells (158.3±12.6% (P<0.001) versus the negative control) while Insulin alone enhanced deoxyglucose-uptake up to 154.7±6.4% (P<0.001). In differentiated 3T3-L1 cells GIP in combination with insulin increased the deoxyglucose-uptake up to 337.7±23.6% versus control (P<0.001). However, insulin caused a rise of deoxyglucose-uptake to 292.3±22.6% (P<0.001) versus the negative control.
These results reveal further evidence for the physiological importance of GIP in glucose metabolism in extra-pancreatic tissues. GIP is able to influence the glucose-uptake in combination with insulin. However, its effects are small in comparison to insulin.