Enhanced insulin sensitivity in extrarenal potassium handling in uremic rats

Abstract

Translocation of potassium to the intracellular compartment is impaired in advanced chronic renal failure. The purpose of this study was to evaluate the role of endogenous insulin in the disposal of an oral potassium load in uremia. Experiments were done on male Sprague-Dawley rats. Chronic renal failure (CRF) was induced by 3/4 nephrectomy. The results show that the addition of oral glucose to a potassium load was more effective in the translocation of potassium to the intracellular compartment in uremic animals. Further, suppression of endogenous insulin secretion with somatostatin caused a much higher increase in plasma potassium (K) of uremic rats (1.09 +/- 0.15 mEq/liter in CRF vs. 0.28 +/- 0.03 mEq/liter in control). Experiments to assess the activity of the Na pump were done in soleus muscles derived from these animals. Although a 50% reduction of the basal Na pump activity was found in the uremic muscles, the addition of insulin 100 mU/ml caused a relatively greater stimulation of ouabain-sensitive 86Rb uptake in the uremic muscle as compared to the control tissue (203% vs. 77% increment). These data suggest a greater sensitivity to insulin action on extrarenal potassium disposal in uremia.

Effect of chronic renal failure on Na,K-ATPase alpha 1 and alpha 2 mRNA transcription in rat skeletal muscle.

“…The characteristics of experimental animals, 3-4 wk after partial nephrectomy (3/4), were similar to those previously described (4). The experimental rats have body weights and blood pH values similar to control rats.…”

“…We have recently shown that the addition oforal glucose to a potassium load was more effective in the translocation of potassium to the intracellular compartment in uremic animals (4). Further, in vitro studies indicated that insulin caused a relatively greater stimulation ofouabain-sensitive 86Rb uptake in the uremic tissue as compared to control soleus muscle (4). These results suggest changes in the expression of the Na,K-ATPase.…”

“…In fact, we and others (2,3) have shown a defect in extrarenal potassium disposal in azotemia, due to a less active sodium pump in skeletal muscle (4,5); whereas an increment in the number of sodium pumps of the secretory epithelia has been described in uremia (6).…”

Effects of recombinant human growth hormone on muscle protein turnover in malnourished hemodialysis patients.

“…However, several observations have indicated an impairment of extrarenal potassium metabolism occurring in CRF (47). Somatostatin administration to fasting rats is followed by a greater increase in plasma potassium in uremic than in normal animals (48). Moreover, the ouabaininhibitable rubidium uptake by skeletal muscle from uremic rats is impaired (49).…”

Hyperkalemia in two patients with diabetes mallitus and chronic kidney disease. Role of disrupted internal potassium balance

“…The effect of dialysis on plasma MBG levels has not been reported thus far, to our knowledge. Uremia also causes peripheral tissue resistance to the hypoglycemic effect of insulin [30], while the effect of insulin on cellular uptake of potassium is unchanged [31] or enhanced [32] Tables 4-5). These findings are consistent with previous findings supporting an added hyperkalemic effect of ketoacidosis in CKD patients [19,21].…”