Luminal glucose does not enhance active intestinal calcium absorption in mice: evidence against a role for Cav1.3 as a mediator of calcium uptake during absorption

Abstract

Intestinal Ca absorption occurs through a 1,25-dihydroxyvitamin D3 (1,25(OH)2D3)–regulated transcellular pathway, especially when habitual dietary Ca intake is low. Recently the L-type voltage-gated Ca channel, Cav1.3, was proposed to mediate active, transcellular Ca absorption in response to membrane depolarization caused by elevated luminal glucose levels after a meal. We tested the hypothesis that high luminal glucose could reveal a role for Cav1.3 in active intestinal Ca absorption in mice. Nine-week-old male C57BL/6 J mice were fed AIN93G diets containing either low (0.125%) or high (1%) Ca for 1 week, and Ca absorption was examined by an oral gavage method using a 45Ca-transport buffer containing 25 mmol/L of glucose or fructose. Transient receptor potential vanilloid 6 (TRPV6), calbindin D9k (CaBPD9k), and Cav1.3 messenger RNA (mRNA) levels were measured in the duodenum, jejunum, and ileum. TRPV6 and CaBPD9k expressions were highest in the duodenum, where active, 1,25(OH)2D3-regulated Ca absorption occurs, whereas Cav1.3 mRNA levels were similar across the intestinal segments. As expected, the low-Ca diet increased renal cytochrome p450-27B1 (CYP27B1) mRNA (P = .003), serum 1,25(OH)2D3 (P < .001), and Ca absorption efficiency by 2-fold with the fructose buffer. However, the glucose buffer used to favor Cav1.3 activation did not increase Ca absorption efficiency (P = .6) regardless of the dietary Ca intake level. Collectively, our results show that glucose did not enhance Ca absorption and they do not support a critical role for Cav1.3 in either basal or vitamin D–regulated intestinal Ca absorption in vivo.