Abstract
The effects of hyperglycemia and hyperinsulinemia on renal handling of sodium, calcium, and phosphate were studied in dogs employing the recollection micropuncture technique. Subthreshold sustained hyperglycemia resulted in an isonatric inhibition of proximal tubular sodium, fluid, calcium, and phosphate reabsorption by 8-14%. Fractional excretion of sodium and phosphate, however, fell (P is less than 0.01) indicating that the increased delivery of these ions was reabsorbed in portions of the nephron distal to the site of puncture and in addition net sodium and phosphate transport was enhanced resulting in a significant antinatriuresis and antiphosphaturia. The creation of a steady state plateau of hyperinsulinemia while maintaining the blood glucose concentration of euglycemic levels mimicked the effects of hyperglycemia on proximal tubular transport and fractional excretion of sodium and calcium. Tubular fluid to plasma insulin ratio fell, similar to the hyperglycemic studies. These results suggest that the effects of hyperglycemia on renal handling of sodium and calcium may be mediated through changes in plasma insulin concentration. In contrast to hyperglycemia, however, hyperinsulinemia cuased a significant fall in tubular fluid to plasma phosphate ratio with enhanced proximal tubular phosphate reabsorption (P is less than 0.02). This occurred concomitantly with a significant inhibition of proximal tubular sodium transport. These data indicate that insulin has a direct effect on proximal tubular phosphate reabsorption, and this effect of insulin is masked by the presence of increased amounts of unreabsorbed glucose in the tubule that ensues when hyperinsulinemia occurs secondary to hyperglycemia. Fractional excretion of phosphate fell significantly during insulin infusion but unlike the hyperglycemic studies, the fall in phosphate excretion could be entirely accounted for by enhanced proximal reabsorption.
MeSH Terms
Absorption
Animals
Biological Transport/drug effects
Dogs
Electrolytes/metabolism
Female
Glucose/pharmacology
Hyperglycemia/metabolism
Insulin/blood,pharmacology
Kidney Tubules/metabolism
Kidney Tubules, Distal/metabolism
Kidney Tubules, Proximal/metabolism
Renal Artery
Sodium/metabolism
Time Factors
Chemicals
Electrolytes
Insulin
Sodium
Glucose
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
DeFronzo R A
Goldberg M
Agus Z S
References (29)
29 references, click to expand
-
The Relationship of Phosphates to Carbohydrate Metabolism: Time Relationship of the Changes in Phosphate Excretion caused by Insulin and Sugar.
Biochem J. 1924;18(5):1170-84
PMID: 16743349
-
THE EFFECT OF FOOD INGESTION ON THE URINARY EXCRETION OF CALCIUM AND MAGNESIUM.
Clin Chim Acta. 1965 Apr;11:354-62
PMID: 14323681
-
IMPAIRED RENAL TUBULAR FUNCTION INDUCED BY SUGAR INFUSION IN MAN.
J Clin Endocrinol Metab. 1964 Dec;24:1318-27
PMID: 14243176
-
Effect of insulin on short-circuit current across isolated frog skin in the presence of calcium and magnesium.
Biochim Biophys Acta. 1963 Jan 15;66:170-2
PMID: 13954055
-
The influence of blood glucose on the renal clearance of phosphate.
J Clin Invest. 1958 Mar;37(3):369-79
PMID: 13513767
-
Interrelations during renal tubular reabsorption in the dog among several anions showing a sensitivity to glucose and phlorizin.
Am J Physiol. 1957 May;189(2):331-8
PMID: 13435368
-
Glucose and phosphate excretion in the cat.
J Physiol. 1954 Jun 28;124(3):613-22
PMID: 13175203
-
Effect in normal man of hyperglycemia and glycosuria on excretion and reabsorption of phosphate.
J Appl Physiol. 1951 Sep;4(3):224-6
PMID: 14897787
-
A rapid method for the determination of para-aminohippuric acid in kidney function tests.
J Lab Clin Med. 1951 Jun;37(6):955-8
PMID: 14850828
-
Interaction between isolated amphibian skin and insulin.
Arch Int Physiol Biochim. 1969 Aug;77(3):527-30
PMID: 4186371
-
Effects of phosphate depletion and parathyroid hormone on renal glucose reabsorption.
Am J Physiol. 1974 Dec;227(6):1422-7
PMID: 4374094
-
Cyclic nucleotide phosphodiesterases.
Adv Cyclic Nucleotide Res. 1973;3:65-98
PMID: 4361529
-
Effects of parathyroid hormone on renal tubular reabsorption of calcium, sodium, and phosphate.
Am J Physiol. 1973 May;224(5):1143-8
PMID: 4349532
-
Mode of action of parathyroid hormone and cyclic adenosine 3',5'-monophosphate on renal tubular phosphate reabsorption in the dog.
J Clin Invest. 1971 Mar;50(3):617-26
PMID: 4322720
-
The effect of glucose on the urinary excretion of sodium and hydrogen ion in man.
Clin Sci Mol Med. 1974 Dec;47(6):589-98
PMID: 4448041
-
A model of the kinetics of insulin in man.
J Clin Invest. 1974 May;53(5):1481-92
PMID: 4856884
-
Micropuncture studies of phosphate transport in the proximal tubule of the dog. The relationship to sodium reabsorption.
J Clin Invest. 1974 Jan;53(1):143-53
PMID: 4808634
-
The effect of glucose on urinary cation excretion during chronic extracellular volume expansion in normal man.
J Clin Invest. 1974 May;53(5):1424-33
PMID: 4825233
-
Proximal tubule potential difference. Dependence on glucose on glucose, HCO 3 , and amino acids.
J Clin Invest. 1973 Jun;52(6):1362-7
PMID: 4703223
-
Tracer microinjection study of renal tubular phosphate reabsorption in the rat.
J Clin Invest. 1972 Sep;51(9):2271-6
PMID: 4639013
-
Effect of glucose and free fatty acid on phosphate transport in dog kidney.
Am J Physiol. 1972 May;222(5):1153-60
PMID: 5022374
-
Stimulation of the secretion of parathyroid hormone during hypoglycemic stress.
J Clin Endocrinol Metab. 1975 Oct;41(4):692-6
PMID: 1176581
-
The effect of insulin on renal handling of sodium, potassium, calcium, and phosphate in man.
J Clin Invest. 1975 Apr;55(4):845-55
PMID: 1120786
-
Control by insulin of sodium potassium and water excretion by the isolated dog kidney.
Pflugers Arch. 1971;323(1):11-20
PMID: 5100564
-
Micropuncture study of handling of phosphate by proximal and distal nephron in normal and parathyroidectomized rat. Evidence for distal reabsorption.
Pflugers Arch. 1970;317(2):93-109
PMID: 5464990
-
A comparison of the effects of glucose ingestion and NH4Cl acidosis on urinary calcium and magnesium excretion in man.
J Clin Invest. 1970 Jul;49(7):1458-65
PMID: 5432375
-
Natriuresis and carbohydrate-induced antinatriuresis after overnight fast and hydration.
Nephron. 1970 Jul;7(4):289-300
PMID: 5426041
-
Micropuncture study of hypertonic mannitol diuresis in the proximal and distal tubule of the dog kidney.
J Clin Invest. 1969 Dec;48(12):2330-40
PMID: 5355344
-
Influence of various nutrients on urinary divalent cation excretion.
J Lab Clin Med. 1967 Aug;70(2):236-45
PMID: 6029056