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 following 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/6J 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 mRNA levels were measured in the duodenum, jejunum and ileum. TRPV6 and CaBPD9k expression were highest in the duodenum, where active, 1,25(OH)2D3-regulated Ca absorption occurs while Cav1.3 mRNA levels were similar across the intestinal segments. As expected, the low Ca diet increased renal cytochrome p450-27B1 (CYP27B1) mRNA (p=0.003), serum 1,25(OH)2D3 (p<0.001) 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=0.6) 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.

Oxidative stress, antioxidants and intestinal calcium absorption

“…TRPV6 would predominate under polarizing conditions between meals, whereas Ca v 1.3 would play a dominant role under depolarizing conditions during digestion, mainly when diet is plentiful in Ca 2+[71] . In contrast, some authors demonstrate that Ca v 1.3 is not critical for active intestinal Ca 2+ absorption in vivo in mice[ 72 ]. Calbindin D 9k in mammals and calbindin D 28k in birds are cytoplasmic proteins that carry the cations as a ferry from the BBM to the BLM[ 73 ].…”

TRPV6 and Cav1.3 Mediate Distal Small Intestine Calcium Absorption Before Weaning

“…Prior work using perfused jejunal loops of adult rats found decreased unidirectional lumen to serosal flux on apical addition of nifedipine and therefore suggested that Ca v 1.3 contributes to intestinal Ca 2+ absorption at later ages 38 . However, their study has been contradicted by further work in rodents 19 . Collectively, these results illustrate the potential role of Ca v 1.3, but not in early postnatal development.…”

“…Previous studies failed to identify transcellular Ca 2+ absorption in the jejunum and ileum while noting significant paracellular secretion in 9- to 15-week-old mice 17, 19. A study using in situ ligated loops in 16-day-old rats measured absorption along the length of the small intestine 37 .…”

“…The molecular components of the proposed transcellular absorption pathway are expressed in the duodenum and large intestine of adult animals, whereas paracellular absorption or secretion predominates in the jejunum and ileum 17, 18, 19. In contrast, existing evidence suggests that alternative Ca 2+ absorption mechanisms are present during development compared with older animals 18, 20, 21.…”

The role of vitamin D in the endocrinology controlling calcium homeostasis

“…However, several studies do not support an essential role for Ca v 1.3 in either basal or vitamin D-stimulated intestinal calcium absorption. (Xue and Fleet, 2009, Reyes-Fernandez and Fleet, 2015). …”