Glucose regulates the maximal velocities of glucokinase and glucose utilization in the immature fetal rat pancreatic islet

Jian Tu, Bernard E. Tuch*

*Corresponding author for this work

    Research output: Contribution to journalArticle

    22 Citations (Scopus)

    Abstract

    The cause of the poor secretion of insulin in response to glucose by the β-cell in the fetal rat pancreas is thought to be immaturity of the metabolism of glucose. Glucokinase (GK), a key enzyme in glycolysis, is the glucose sensor that maintains glucose homeostasis in the adult β-cell; its role in the fetal β-cell has not been determined. The aim of this study was to examine whether GK was functional in phosphorylation of glucose in the fetal islet, and if so, to determine what factors regulated this activity. Similac K(m) values were found in both fetal and adult islets: 7.4 vs. 7.7 mmol/l. The maximal GK velocity (V(max)) of the fetal islet and the contribution of GK to total glucose phosphorylation were also not significantly different from their adult counterparts. Western blot analysis of protein extracts from fetal and adult islets confirmed the presence of GK at 52 kDa. To determine if glucose had any effect on the V(max) of GK, islets were cultured for 7 days in medium containing low (1.4 or 2.8 mmol/l), normal (5.6 mmol/l), or high (11.2 or 16.8 mmol/l) concentrations of glucose. The maximal GK velocity increased linearly with increasing concentrations of glucose (r = 0.93; P < O.01). To determine whether it was possible to up- and down-regulate V(max) of GK, islets were cultured in either a low (1.4 mmol/l) or high (30 mmol/l) concentration of glucose for 7 days and then switched to the opposite concentration for a further 3 days. The V(max) of GK in the fetal islet was upregulated 3.8-fold when the glucose concentration was raised. Conversely, the V(max) was downregulated 3.6-fold when the glucose concentration was lowered. The same phenomenon was also observed in the adult islet. These data indicate that GK is the glucose sensor for the fetal rat islet, just as it is for the adult islet. Since glucose did not cause insulin secretion from the fetal islet, it was important to examine whether this substrate had any effect on its own metabolism. Glucose utilization was estimated, and its V(max) was found to increase linearly with increasing concentrations of glucose (r = 0.96; P < O.01). We conclude that the inability of the fetal rat β-cell to secrete insulin in response to glucose cannot be explained by immaturity of GK or the glycolytic pathway.

    Original languageEnglish
    Pages (from-to)1068-1075
    Number of pages8
    JournalDiabetes
    Volume45
    Issue number8
    Publication statusPublished - 1996

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