Comparison of insulin action on glucose versus potassium uptake in humans

Abstract

Background and objectives: Insulin has several physiologic actions that include stimulation of cellular glucose and potassium uptake. The ability of insulin to induce glucose uptake by cells is impaired in type 2 diabetes mellitus, but whether potassium uptake is similarly impaired is not known. This study examines whether the cellular uptake of these molecules is regulated in concert or independently.

Design, setting, participants, & measurements: Thirty-two nondiabetic and 13 type 2 diabetic subjects with normal GFR were given a similar, constant metabolic diet for 8 days. On day 9, they were subjected to a hyperinsulinemic euglycemic clamp for 2 hours. Serum and urinary chemistry were obtained before and during the clamp. Glucose disposal rate was calculated from glucose infusion rate during hyperinsulinemic euglycemia. Intracellular potassium and phosphate uptake were calculated by the reduction of extracellular potassium or phosphate content corrected for urinary excretion.

Results: Although glucose disposal rate tended to be lower in type 2 diabetics, cellular potassium uptake was similar between diabetics and nondiabetics. Additionally, although glucose disposal rate was lower with increasing body mass index (R² = 0.362), cellular potassium (R² = 0.052), and phosphate (R² = 0.002), uptake rates did not correlate with body mass index. There was also no correlation between glucose disposal rate and potassium (R² = 0.016) or phosphate uptake (R² = 0.053). Conclusions Insulin-stimulated intracellular uptake of glucose and potassium are independent of each other. In type 2 diabetes, potassium uptake is preserved despite impaired glucose disposal.

Figure 1.

Relationship of (A) glucose, (B) potassium, and (C) phosphate uptake as a function of body mass index (BMI). Forty-five subjects with a wide range of BMIs underwent hyperinsulinemic euglycemic clamp. Glucose disposal rate was calculated from the glucose infusion required to maintain euglycemia. Potassium and phosphate uptake were calculated as the reduction in extracellular potassium or phosphate corrected for urinary excretion. The correlation coefficient was calculated for the relationship between the x and y values as well as the P value for the R².

Figure 2.

Relationship between uptake of three solutes: (A) potassium versus glucose, (B) phosphate versus glucose, and (C) phosphate versus potassium. Forty-five subjects with a wide range of BMIs underwent hyperinsulinemic euglycemic clamp. Glucose disposal rate was calculated from the glucose infusion required to maintain euglycemia. Potassium and phosphate uptake were calculated as the reduction in extracellular potassium or phosphate corrected for urinary excretion. The correlation coefficient was calculated for the relationship between the x and y values as well as the P value for the R².