Glucose transporters in pancreatic islets

Abstract

The fine-tuning of glucose uptake mechanisms is rendered by various glucose transporters with distinct transport characteristics. In the pancreatic islet, facilitative diffusion glucose transporters (GLUTs), and sodium-glucose cotransporters (SGLTs) contribute to glucose uptake and represent important components in the glucose-stimulated hormone release from endocrine cells, therefore playing a crucial role in blood glucose homeostasis. This review summarizes the current knowledge about cell type-specific expression profiles as well as proven and putative functions of distinct GLUT and SGLT family members in the human and rodent pancreatic islet and further discusses their possible involvement in onset and progression of diabetes mellitus. In context of GLUTs, we focus on GLUT2, characterizing the main glucose transporter in insulin-secreting β-cells in rodents. In addition, we discuss recent data proposing that other GLUT family members, namely GLUT1 and GLUT3, render this task in humans. Finally, we summarize latest information about SGLT1 and SGLT2 as representatives of the SGLT family that have been reported to be expressed predominantly in the α-cell population with a suggested functional role in the regulation of glucagon release.

SGLT2 is not expressed in pancreatic α- and β-cells, and its inhibition does not directly affect glucagon and insulin secretion in rodents and humans

“…This lack of effect was surprising because it was expected that the characteristics of SGLT1 (cotransport of glucose with 2 Na + and K m of 2 mM [ 51 ]) help to concentrate glucose inside the cell and that SGLT1 inhibition would affect glucose fluxes across the plasma membrane. However, given the relatively low expression of SGLT1 in α-cells (vs the gut), it is possible that other glucose transporters, such as GLUT1 or GLUT11, which have a high affinity for glucose, are expressed at the plasma membrane and are present in human α-cells [ 18 , 31 , 32 ], keeping glucose flux unaltered in our experimental conditions when SGLT1 was inhibited. It is also unknown whether the SGLT1 transcript in α-cells generates a functional protein.…”

“…The rise in ketone body levels results from their increased production rather than decreased renal clearance [ 15 ]. The potential causes of these metabolic responses are the SGLT2i-mediated increase in blood glucagon levels and decrease in blood insulin levels [ 3 , 8 , 10 ], but the mechanisms by which gliflozins increase glucagonemia are highly contested [ 7 , [16] , [17] , [18] ]. Some studies have suggested that gliflozins act directly on α-cells that express SGLT2 [ [19] , [20] , [21] , [22] ].…”

Natural Compound α-PGG and Its Synthetic Derivative 6Cl-TGQ Alter Insulin Secretion: Evidence for Diminishing Glucose Uptake as a Mechanism

“…It is well established that insulin production and secretion from pancreatic beta-cells is a multi-step, vigorously regulated process that is initiated from the glucose transport-mediated by Glut2 and followed by consequent increases in glycolytic rate and ATP production. 7 , 58 , 59 ATP/ADP ratios are critical regulators of glucose-stimulated insulin secretion. In our study, inhibition of Glut2-mediated glucose transport by our compounds was speculated and confirmed by subsequent glucose uptake assays in both mouse pancreatic islets and rat INS-1832/13 cells.…”

“… 5 , 6 Adipocytes sense increases in circulating levels of insulin to recruit more Glut4 transporter to the cell surface to take up glucose, whereas in contrast, pancreatic islets use transporter 2 (Glut2)-mediated glucose transport (Glut1 and Glut 3 in humans) as the primary sensor of circulating levels of blood glucose. 7 , 8 The relationship between glucose and insulin thus defines the biological actions of peripheral adipocytes and pancreatic beta-cells in very different ways, but both making important contributions to the systemic regulation of glucose.…”

Fanconi–Bickel Syndrome: A Review of the Mechanisms That Lead to Dysglycaemia

“…GLUT2 maintains glucose homeostasis by regulating the transepithelial uptake of glucose in the epithelial cells of basolateral membrane, glucose reabsorption in the kidney proximal tubule, glucose uptake and release from the sinusoidal membrane of the liver cells, and glucose regulated insulin secretion from pancreatic β-cells [ 22 ]. For more comprehensive reviews on the physiological roles of GLUT2, please see references [ 23 , 24 , 25 ].…”