On the track to the beta-cell.

Abstract

The imaging and quantification of the endocrine pancreas by a non-invasive procedure remains a challenge. In the prolongation of prior work on selected succinic acid esters and monosaccharide esters, it is proposed that D-mannoheptulose, which might be transported across the plasma membrane at the intervention of GLUT-2, could be used to label preferentially the endocrine moiety of the pancreatic gland. This heptose is taken up more efficiently by hepatocytes and islet cells, than by erythrocytes, parotid cells, acinar pancreatic cells or tumoural islet cells of either the RINm5F or INS-1 line. Likewise, D-mannoheptulose only inhibits D-glucose metabolism in hepatocytes and isolated islets. Its hexaacetate ester, however, inhibits the catabolism of the hexose in all cell types. The uptake of D-mannoheptulose represents a carrier-mediated process. Human islets behave like rat islets in terms of D-mannoheptulose uptake and inhibition by the heptose of both D-glucose metabolism and insulinotropic action. The use of radiolabelled analogs of D-mannoheptulose suitable for imaging of the endocrine pancreas is discussed. In the same perspective, it is proposed that advantage could be taken of the much greater accumulation of glycogen in insulin-producing cells, as compared to other pancreatic cell types, in situations of sustained hyperglycaemia.