Renal potassium handling in carriers of the Gly40Ser mutation of the glucagon receptor suggests a role for glucagon in potassium homeostasis. Issue 8 (19th April 2018)

• Record Type: Journal Article
• Authors: Bankir, Lise; Barbato, Antonio; Russo, Ornella; Crambert, Gilles; Iacone, Roberto; Bouby, Nadine; Perna, Ludovica; Strazzullo, Pasquale
• Is Part Of: Physiological reports. Volume 6:Issue 8(2018)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2018-04-19
• Subjects: Glucose -- Insulin -- Mendelian randomization -- Sodium -- TTKG -- Urea; Physiology -- Periodicals; 571
• DOI: 10.14814/phy2.13661
• Languages: English
• ISSNs: 2051-817X

Abstract

Abstract: Plasma potassium concentration (PK ) is tightly regulated. Insulin is known to favor potassium entry into cells. But how potassium leaves the cells later on is not often considered. Previous studies in rats showed that glucagon infusion increased urinary potassium excretion dose‐dependently and reversibly. This prompted us to investigate the possible influence of glucagon on potassium handling in humans. We took advantage of the Gly40Ser mutation of the glucagon receptor (GR) that results in a partial loss of function of the GR. In the Olivetti cohort (male workers), 25 subjects who carried this mutation were matched 1:4 to 100 noncarriers for age and weight. Estimated osmolarity of serum and 24‐h urine (Sosm and Uosm, respectively) was calculated from the concentrations of the main solutes: [(Na+K)*2 + urea (+glucose for serum)]. Transtubular potassium gradient (TTKG), reflecting the intensity of K secretion in the distal nephron, was calculated as [(urine K/serum K)(Uosm /Sosm )]. There was no significant difference in serum K, or 24‐h urine urea, Na and K excretion rates. But urine K concentration was significantly lower in carriers than in noncarriers. Means (interquartile range): 38 (34–43) versus 47 (43–51) mmol/L, P = 0.030. TTKG was also significantly lower in carriers: 4.2 (3.9–4.6) versus 5.0 (4.7–5.2), P = 0.015. This difference remained statistically significant after adjustments for serum insulin and 24‐h Na and urea excretions. These results in humans suggest that glucagon stimulates K secretion in the distal nephron. Thus, in conjunction with insulin, glucagon may also participate in K homeostasis by promoting renal K excretion. Abstract : Plasma potassium concentration is tightly regulated. Insulin is known to favor potassium entry into cells. But how potassium leaves the cells later on is not often considered. In rats, glucagon was shown to increase significantly, dose‐dependently, and reversibly urinary potassium excretion. The present study shows, in a human cohort, that subjects carrying a mutation of the glucagon receptor that induces a partial loss of function, exhibit a reduced urinary potassium concentration and a reduced TTKG, an index of potassium secretion in the collecting duct. These results suggest that glucagon, in conjunction with insulin, may participate in potassium homeostasis by its influence on urinary potassium excretion.