Laboratory Investigation

Kidney International (1983) 24, 10–15; doi:10.1038/ki.1983.120

Effects of somatostatin on phosphate transport: Evidence for the role of basal insulin

Kai Lau1, Jay Guntupalli1 and Bonnie Eby1

1Division of Nephrology, Department of Internal Medicine, The University of Michigan, Ann Arbor, Michigan

Correspondence: Dr K Lau, Division of Nephrology, Department of Internal Medicine, The University of Michigan, D3238 South Ambulatory Care Building, Ann Arbor, Michigan 48109, USA

Received 8 April 1982; Revised 12 November 1982.

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Abstract

Effects of somatostatin on phosphate transport: Evidence for the role of basal insulin. Previous studies suggest that normoglycemic hyperinsulinemia is associated with enhanced proximal tubule and overall renal phosphate (PO4) reabsorption. It is unclear whether the basal level of insulin also regulates PO4 transport. Furthermore, the role of parathyroid hormone, the associated antinatriuresis, and the distal nephron is uncertain. To examine these issues, clearance and recollection micro-puncture studies were performed in volume-expanded parathyroidectomized rats. Infusion of des-Asn5-D-Trp8-D-Ser13, a somatostatin analogue highly selective for insulin at 10 microg/kg/hr, decreased plasma insulin (12.6 to 2.8 microU/ml), and increased plasma glucose (93 to 140 mg%) and fractional excretion (FE) of sodium (Delta = 2.5%). The clearance of PO4 (118 to 297 microl/min) and FEPO4 (2.4 to 6.8%) was increased. Continued somatostatin infusion produced a sustained phosphaturia whereas the addition of insulin (0.10 U/kg/hr) abolished the phosphaturic effects. Separate loading with saline and glucose to achieve comparable DeltaFENa (2.9%) and Deltaplasma glucose (52 mg%) did not increase PO4 excretion. Between basal and experimental phases, there was no difference in plasma ultrafiltrable PO4, GFR, or segmental fluid reabsorption. While fractional delivery of PO4(FDPO4) was unchanged in the control, somatostatin increased FDPO4 to late proximal (50 vs. 32%), early distal (28.2 vs. 13.4%), late distal tubules (11.8 vs. 6.4%), and to the urine (8.5 vs. 4.9%). These data indicate that (1) insulin deficiency, as produced by somatostatin infusion, impairs tubular PO4 reabsorption, suggesting an important role for the basal level of insulin in renal PO4 homeostasis; (2) the phosphaturia of somatostatin is independent of the concomitant natriuresis, hyperglycemia, PTH, and changes in plasma PO4; and (3) insulinopenia reduces PO4 transport in the proximal convoluted tubule and the distal nephron.

Effets de la somatostatine sur le transport du PO4: Preuve d'un rôle de l'insuline basale. Des études antérieures suggèrent que l'hyperinsulinémie normoglycémique est associée à une augmentation de la réabsorption rénale de phosphate (PO4) globale et dans le tubule proximal. On ne sait pas bien si le niveau basal d'insuline régule également le transport de PO4. En outre, le rôle de l'hormone parathyroïdienne, de l'antinatriurèse associée et du néphron distal est incertain. Afin d'examiner ces possibilités, des études de clearance et de microponction avec recollection ont été effectuées chez des rats parathyroïdectomisés en expansion volémique. La perfusion de des-Asn5-D-Trp8-D-Ser13, un analogue de la somatostatine hautement sélectif pour l'insuline à 10 microg/kg/hr, a diminué l'insuline plasmatique (12.6 à 2.8 microU/ml), augmenté la glycémie (de 93 à 140 mg%) et l'excrétion fractionnelle (FE) de sodium (Delta = 2.5%). La clearance de PO4 (118 à 297 microl/min) et FEPO4 (2.4 à 6.8%) se sont élevées. Une perfusion prolongée de somatostatine a entraîné une phosphaturie persistante tandis que l'addition d'insuline (0.10 U/kg/hr) a aboli les effets phosphaturiants. Une charge séparée avec du soluté salé et du glucose pour obtenir un Delta FENa (2.9%) et un Delta glycémie (52 mg%) comparables n'a pas augmenté l'excrétion de PO4. Entre les phases basale et expérimentale il n'y avait pas de différence dans le PO4 ultrafiltrable, le GFR ni la réabsorption segmentaire de fluide. Tandis que la fraction délivrée de PO4(FDPO4) était inchangée pendant le contrôle, la somatostatine a augmenté FDPO4 aux tubules proximal tardif (50 contre 32%), distal précoce (28.2 contre 13.4%) et tardif (11.8 contre 6.4%), et à l'urine (8.5 contre 4.9%). Ces données indiquent que (1) la carence en insuline résultant d'une perfusion de somatostatine altère la réabsorption tubulaire de PO4, suggérant un rôle important de la concentration de l'insuline de base dans l'homéostasie du PO4; (2) la phosphaturie due à la somatostatine est indépendante de la natriurèse concomitante, de l'hyperglycémie, de la PTH, et des modifications du PO4 plasmatique; (3) l'insulinopénie réduit le transport de PO4 dans le tubule contourné proximal et le néphron distal.

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