Metabolism of Glucose in the Islets of Langerhans

Abstract

Abstract The levels of glycogen, glucose, glucose-6-P, the sum of fructose diphosphate plus dihydroxyacetone-P, ATP, and the pyridine nucleotides were measured in endocrine and exocrine tissue of the pancreas of obese hyperglycemic mice. Sorbitol was determined in both types of tissue after a single intravenous injection of the compound. Quantitative histochemical techniques were employed. The necessary analytical sensitivity was achieved by working in small volumes under oil and by using enzymatic methods in combination with cycling assays for pyridine nucleotides. In islet tissue the levels of glycogen and glucose were much higher than in the acinar tissue. Concentrations of glucose in islets were equal to those in blood over a concentration range from 5 to 100 mm. Acinar tissue, on the contrary, contained much less glucose than the blood. When blood glucose levels were low, glucose-6-P levels were about the same in islet and acinar tissue, but with increasing blood glucose, glucose-6-P rose to very high levels in islets whereas acinar levels increased only to a moderate degree. In islets, fructose diphosphate plus dihydroxyacetone-P also increased greatly when blood glucose rose. The velocities of glucose penetration and of glucose-6-P accumulation in β-cells were as rapid as other authors have observed to be true for the onset of insulin release. It was found that sorbitol can enter islet cells, but the rate appeared to be much slower than in the case of glucose. The extracellular space of islets and acini, based on the rapid initial distribution of sorbitol between serum and tissue, was calculated to be 39 and 26%, respectively, of the tissue water. A study in vitro of glucose phosphorylation by islet tissue indicated the presence of two enzymes, one with high and one with low affinity for glucose. Islet but not acinar tissue hydrolyzed glucose 6-phosphate. A scheme for the early steps of glucose metabolism in the β-cells is presented, and the possible significance of the findings regarding the mechanism of insulin release is discussed.