Expression and regulation of glucokinase in rat islet beta- and alpha-cells during development

Glucokinase (GK) is the rate-limiting enzyme in the glycolytic pathway of t he beta-cell and, even in the rat fetus at 22-days gestation, immediately b efore birth, acts as a sensor of glucose influencing the rate of glucose ut ilization. However, when GK first appears in islets during beta-cell develo pment is unknown. Whether GK is expressed in fetal glucagon-producing cells is also unknown. To determine this information, fetal rat islets were exam ined at 16-, 18-, and 22-days gestation. GK was identified immunocytochemic ally in both beta- and alpha-cells at all these ages, with the number of GK immunoreactive cells positively correlated to the fetal age from 16-22 day s. Western blot analysis of islet protein extracts demonstrated the presenc e of GK, at 52 kDa, at 16 days and thereafter. To determine whether glucose had any effect on regulation of GK biosynthesis, fetal islets were culture d in medium containing a wide range of concentrations of glucose for 7 days . The amount of GK protein was significantly decreased in low concentration s of glucose and augmented at high concentrations. In conclusion, GK was ex pressed in both beta- and alpha-cells in fetal rat islets during developmen t GK is an integral part of the function of both of these cells at all stag es in the development of the fetal islet.