Investigating the Expression and Function of the Glucose Transporter GLUT6 in Obesity.

Obesity-related insulin resistance is a highly prevalent and growing health concern, which places stress on the pancreatic islets of Langerhans by increasing insulin secretion to lower blood glucose levels. The glucose transporters GLUT1 and GLUT3 play a key role in glucose-stimulated insulin secretion in human islets, while GLUT2 is the key isoform in rodent islets. However, it is unclear whether other glucose transporters also contribute to insulin secretion by pancreatic islets. Herein, we show that () is markedly upregulated in pancreatic islets from genetically obese leptin-mutant () and leptin receptor-mutant () mice, compared to lean controls. Furthermore, we observe that islet expression positively correlates with body mass index in human patients with type 2 diabetes. To investigate whether plays a functional role in islets, we crossed knockout mice with C57BL/6 mice. Pancreatic islets isolated from mice lacking secreted more insulin in response to high-dose glucose, compared to mice that were wild type for . The loss of in mice had no adverse impact on body mass, body composition, or glucose tolerance at a whole-body level. This study demonstrates that plays a role in pancreatic islet insulin secretion in vitro but is not a dominant glucose transporter that alters whole-body metabolic physiology in mice.