Jojiro Nakada

Atrial natriuretic peptides stimulate renal gluconeogenesis

Atrial natriuretic peptide (5-28AA; ANP) and atrial extract (ANS) stimulated rat renal gluconeogenesis in cortical tubule suspension in a dose dependent fashion only from substrates that enter gluconeogenesis via phosphoenol-pyruvate carboxylase. The effects of ANP and ANS were significantly potentiated by cAMP and cGMP, whereas methoxamine showed no effect. Extracellular calcium revealed a key role for ANP and ANS response to gluconeogenesis: a concentration of calcium higher than 1 mM was essential. Isolated cells from cortex which lost cell membrane polarity by warming but responded solely to cAMP and cGMP showed no effect by ANP nor ANS. These data suggest that ANP or ANS may act mainly from the basolateral site in the proximal tubule cell and promote gluconeogenesis through cAMP and/or cGMP system.

Alterations of gluconeogenesis by ischemic renal injury in rats.

This study was designed to determine changes in one metabolic function, gluconeogenesis (GLG), after ischemic renal injury. Tubule suspensions were prepared by collagenase treatment of SD rat kidneys on 1, 3, and 7 days after left renal artery and vein occlusion for 0-90 min and incubated in Krebs-Henseleit buffer with or without 2 mM pyruvate or malate aerobically. Glucose contents were assayed photometrically. On days 1 and 3 after ischemia for longer than 60 min, serum creatinine levels rose significantly. The tendency of increase of GLG was observed on days 1 and 3 after 10-60 min of ischemia. GLG increased significantly on day 1 after 30-min ischemia. On the other hand, GLG decreased significantly on day 1 after 90-min treatment. Morphologic damage was limited to the corticomedullary region on days 1 and 3 after ischemic times of 30 and 60 min. These results suggest that renal GLG is stimulated to supply energy for ATP decrease by ischemia and for further regeneration in extraproximal segments along the nephron.

Evidence that Alpha-1-Adrenergic Stimuli Specifically Increase Gluconeogenesis of the Isolated Proximal Convoluted Tubule in the Rat

Isolated kidney-cortical tubule suspensions and microdissected nephron segments from fed rats were used to study the action of catecholamines on gluconeogenesis. Gluconeogenesis from rat tubule suspension incubated with 5 mM pyruvate was stimulated maximally by 10(-5) M methoxamine, an alpha 1-selective agonist, and 10(-6) M noradrenaline by 29.2 +/- 5.2% (mean +/- SEM) and 32.6 +/- 2.9%, respectively. These effects were completely inhibited by 10(-7) M prazosin, a beta 1-selective antagonist. Yohimbine, an alpha 2-antagonist, also inhibited the effect, but only at a higher concentration (5 X 10(-5) M). Gluconeogenesis was not stimulated by isoproterenol, a alpha-agonist, at any concentrations between 10(-5) and 10(-7) M. With microdissected nephron segments, only the proximal tubule possessed gluconeogenic activity. Within the proximal tubule, the proximal convoluted tubule (PCT) revealed higher gluconeogenic activity than the proximal straight tubule (PST). Methoxamine at 10(-5) M stimulated gluconeogenesis in PCT, whereas in PST no increase of gluconeogenesis was observed. From these results, it can be concluded that an alpha 1-adrenergic agonist specifically stimulates renal gluconeogenesis in PCT, but not in PST.