[Glucose transporters. Physiology and physiopathology]. / Transporteurs de glucose. Physiologie et physiopathologie.

Glucose transport is an important step in the regulation of glucose homeostasis. Two types of transport systems are described: active transport accumulates glucose in specific cells, whereas facilitative transport equilibrates blood glucose and intracellular glucose inside all mammalian cells. At the present time, different levels of facilitative transport regulation are known. Facilitative transport is achieved by 5 different isoforms; each isoform has its own characteristics and is subjected to tissue-specific regulation. Alteration of glucose transporters expression may be involved in a physiopathological situation such as diabetes which is characterized by insulin resistance of peripheral tissues and impaired insulin secretion by beta pancreatic cells. Thus, Glut 2 expression is reduced in the beta cells of diabetic rats. The reduction of Glut 2 expression correlates with, and may contribute to the loss of glucose-stimulated insulin secretion. However, Glut 2 expression in liver remains unaltered. The insulin resistance of peripheral tissues may be explained in adipose tissue by a decrease in Glut 4 expression. In skeletal muscle, Glut 4 expression remains constant whatever the physiological or physiopathological situation.

Glucose turnover rate in newborn rats.

In starved newborn rats an increase in glucose turnover rate was observed 4 and 6h after birth, but a dramatic fall occurred at 16h. In suckling newborn rats, no decrease in glucose turnover rate was observed at 16h. The metabolic clearance of glucose did not change in fed or starved animals. The results are discussed in relation to metabolic adaptation to extra-uterine life.

Plasma amino acid levels and development of hepatic gluconeogenesis in the newborn rat.

The metabolism of endogenous and exogenous amino acids has been characterized during a 16-h fast after birth in the rat. Eighteen of 22 amino acids showed a decrease in plasma concentration up to 16 h, the most profound and sustained changes affecting those quantitatively important in gluconeogenesis. The hepatic accumulation of injected [14C]aminoisobutyric acid showed a progressive rise after birth. The in vivo conversion of 14C-labeled lactate, alanine, serine, and glutamine to [14C]glucose increased for 6 h, but all except glutamine showed a decline by 16 h. The in vitro conversion of several gluconeogenic substrates (10mM), however, increased with time in each instance. These data confirm that the capacity for hepatic gluconeogenesis and maintenance of blood glucose concentration appears immediately after birth. Nevertheless, profound hypoglycemia recurs at 16 h and responds only minimally and transiently to exogenous gluconeogenic substrate loads. In contrast, the fed newborn maintains normoglycemia, higher endogenous amino acid levels, and the capacity for substrate conversion at this time. The mechanism for stimulation of hepatic gluconeogenic pathways thus is present in both fasted and fed neonatal rats. However, owing to insufficient energy sources to sustain gluconeogenesis and to inadequate gluconeogenic substrate, the rat is unable to maintain normoglycemia if fasted 16 h.

Effects of exogenous hormones and glucose on plasma levels and hepatic metabolism of amino acids in the fetus and in the newborn rat.

The present study examines the role of insulin, glucagon and cortisol in the regulation of gluconeogenesis from lactate and amino acids in fetal and newborn rats. Injection of glucagon in the full-term fetal rat caused a rise in glucose (and insulin) and a fall in blood levels of most individual amino acids, stimulated hepatic accumulation of 14C-amino isobutyric acid and 14C-cycloleucine and increased the conversion of 14C lactate, alanine and serine to glucose in vivo and in vitro (liver slices). Such changes were equivalent to the changes seen in 4 h old newborn rats. When glucagon was administered at birth, little difference was observed between control and treated animals in plasma amino acids and a smaller increment in conversion of 14C substrate to glucose occurred. By contrast, insulin injection at birth caused hypoglycemia, suppression of levels of certain amino acids and inhibition of conversion of 14C substrates into glucose. Glucose injection at birth caused elevated glycemia and plasma insulin and suppression of most amino acid levels and of conversion of 14C substrate into glucose. Cortisol injection at birth caused a marked, generalized by hyperaminoacidemia, a stimulation of glucagon secretion and of conversion of 14C substrates into glucose. These observations support the thesis that glucagon plays a major role in the induction of hepatic gluconeogenesis and that insulin acts as an antagonist hormone.