The Role of the Pancreas in Vitamin B12 Absorption: Studies of Vitamin B12 Absorption in Partially Pancreatectomized Rats

Abstract

A iB S T R A C T The effect of partial pancreatectomy(80-90%,) on vitamin Bn absorption was studied in the rat. The absorption of 5 ng of^'Co-labeled vitamin B1u was significantly reduced from 70 ±2.5% (mean +SE) in control and sham-operated rats to 32 ±2.6% in partially pancreatectomized rats. Hog pancreatic extract (0.17 g/kg) improved vitamin B12 absorption from 30.0 to 61.0% in partially pancreatectomized rats but did not alter vitamin B,2 absorption in control rats. Chloramphenicol did not enhance vitamin B12 absorption in partially pancreatectomized rats with pancreatic extractimproved vitamin B12 malabsorption. The partially pancreatectomized rats with pancreatic extract-improved vitamin B12 malabsorption were sacrificed and the stomach and small bowel studied in vitro to further define the pathogenesis of the vitamin B12 malabsorption. Rat gastric intrinsic factor stimulated vitamin B12 uptake by intestinal sacs prepared from partially pancreatectomized rats 3.1-fold. Gastric intrinsic factor prepared from partially pancreatectomized rats was as effective in promoting vitamin B12 uptake by rat intestinal sacs as intrinsic factor prepared from control rats. These data indicate that partially pancreatectomized rats develop an abnormality in the absorption of labeled vitamin B12 which can be corected by pancreatic extract. The vitamin B12 malabsorption is due to neither an alteration in gastric intrinsic factor activity nor an impairment of the intrinsic factor-vitamin B12 receptor in the intestine. It is suggested that in the partially pancreatectomized rats the intrinsic factor-vitamin B12 complex exists in a form which is not available for absorption. INTRODUCTIONAlthough several patients with pancreatic exocrine insufficiency have been noted to poorly absorb vitamin B,2 the importance of normal pancreatic function for optimal vitamin Bi absorption is generally not appreciated 1-5). Furthermore, the pathogenesis of the observed vitamin B12 absorptive defect has not been clarified.The relationship between the pancreas and the intestinal absorption of vitamin B12 was studied by measuring the absorption of this vitamin in rats subjected to partial pancreatectomy. The results demonstrate (a) that the partially pancreatectomized rat has a defect in vitamin B12 absorption, (b) that the administration of hog pancreatic extract restores vitamin B12 absorption to normal, (c) that intrinsic factor extracted from the gastric mucosa -of partially pancreatectomized rats stimulates vitamin Bn absorption in vitro, and (d) that gastric intrinsic factor stimulates vitamin B12 uptake in gut sacs prepared from partially pancreatectomized rats. These data indicate that partially pancreatectomized rats develop a defect in vitamin B12 absorption which is due to neither an alteration in gastric intrinsic factor activity nor to an impairment of the intrinsic factor-vitamin B12 receptor in the intestine.

Characterization of Ileal Vitamin B12 Binding Using Homogeneous Human and Hog Intrinsic Factors

“…This consideration is important since it suggests that under physiological in vivo conditions, IF-Bi2 binding to ileal IF-Br2-binding sites might be different from that observed with homogeneous IF isolated from gastric juice and gastric mucosa. Other recent studies (34)(35)(36), demonstrating B12 malabsorption in humans and rats with pancreatic insufficiency and its correction with pancreatic extracts and highly purified preparations of trypsin, suggest that differences might exist between in vivo and in vitro ileal IF-B,2 binding.…”

Effect of Proteolytic Enzymes on the Binding of Cobalamin to R Protein and Intrinsic Factor

“…Studies in partially pancreatectomized rats (9) have shown that ileal receptors for IF-Cbl are present in normal amounts and that they function normally in terms of binding the IF-Cbl complex. Cbl malabsorption in humans with pancreatic insufficiency is not corrected by the oral administration of antibiotics nor is it corrected by binding Cbl to human gastric juice or crude hog IF in vitro and then administering it either orally or in the latter case directly into the distal ileum (3).…”

Trypsin-Like Nature of the Pancreatic Factor That Corrects Vitamin B12 Malabsorption Associated with Pancreatic Dysfunction

“…Vitamin B,, absorption studies in rats. Partial pancreatectomies were performed on male albino rats2 as described by Scow (6) and modified by Toskes and Deren (4).' After a suitable recovery period, 1 ml of '7Co-labeled vitamin B,2 containing 5 ng of vitamin B12 (13-15 ,uCi/,ug) was administered via gastric tube to fasted rats.…”

“…Vitamin B12 malabsorption occurs in some patients with chronic pancreatic exocrine insufficiency (1)(2)(3) and in rats subjected to partial pancreatectomy (4). Although hog pancreatic extract corrects the absorptive defect in both humans and animals (1,2,4), the precise constituent in the pancreatic extract responsible for the enhancement of vitamin B12 absorption has not been determined.…”

“…Although hog pancreatic extract corrects the absorptive defect in both humans and animals (1,2,4), the precise constituent in the pancreatic extract responsible for the enhancement of vitamin B12 absorption has not been determined.…”