A submucosal mechanism of action for prostaglandin E2 on hexose absorption and metabolism in mouse intestine.

Abstract

SUMMARY1. The involvement of prostaglandin E2 (PGE2) in hexose absorption and metabolism was studied in mouse small intestinal villus cells.2. Phlorizin-sensitive, Na+-dependent a-methyl-D-glucoside (a-MG) uptake (0-8 mM) during 2 min cell incubations (37 'C) was 74+4 nmol (mg protein)-'. Maximal uptake was 110+8 nmol (mg protein)-', representing an accumulation of 50-fold. Metabolism of D-glucose (5 mM) to L-lactate was 38 nmol min' (mg protein)-'.3. Incubation of isolated cells with indomethacin or PGE2 did not affect a-MG uptake or D-glucose metabolism. By including indomethacin during cell isolation from whole intestine, a-MG uptake was inhibited dose dependently (50-250 /M) by up to 70% (P < 0-001). PGE2 present during both isolation and incubation inhibited by 85 % (P < 0-001 ) at 1 #tM and by 27 % (P < 0 05) at 0-1 M, with no effect at lower concentrations. ac-MG uptake was reduced to 38% (P < 0-01) when 1 /LM-PGE2 and 250 /M-indomethacin were presented in combination. When present during cell isolation and incubation, 1 gzM-PGE2 inhibited lactate production by 24 % (P < 0 05), except when present in combination with 250 ,tm-indomethacin. Indomethacin, itself, had no effect on lactate production. 4. A submucosal mechanism is proposed to account for the observed inhibitory effects of PGE2 on brush-border uptake of x-MG and cellular lactate production. Indomethacin appears to exert not only an effect of its own, possibly via PGindependent actions within the submucosa, but at high concentrations also disrupts the effects of exogenously applied PGE2.

Acute increase, stimulated by prostaglandin E2, in glucose absorption via the sodium dependent glucose transporter-1 in rat intestine

“…This is supported by the direct stimulatory effect of PGE 2 on 3- O -[ 14 C]methylglucose uptake in isolated villus tip enterocytes (fig 3). In a previous study with mice enterocytes, PGE 2 did not alter α-methylglucose uptake13; this discrepancy with the present finding cannot be readily explained at present.…”

Acute and chronic effects of pancreatic glucagon on sugar transport across the brush‐border and basolateral membranes of rat jejunal enterocytes

“…In conclusion, we have demonstrated for the first time a direct rapid stimulatory effect of glucagon on brush-border sugar transport and a delayed effect of the hormone at the basolateral membrane of enterocytes. Together with other recent observations of direct modulation of enterocyte sugar transport under a variety of conditions (Dempster & Kellett, 1992;Pennington et al 1992;, our results imply that the control of enterocyte sugar transport is mediated by a complex array of systemic and local factors.…”

“…Interestingly, whilst hyperglycaemia and luminal glucose appear to influence transport at the basolateral membrane of the enterocyte (Maenz & Cheeseman, 1986;Karasov & Debnam, 1987), data from this present study indicate that the brush-border membrane is also a locus for rapid adaptation. In this context, recent studies have shown that bradykinin ) and prostaglandinE2 (Dempster & Kellett, 1992) are able to rapidly influence enterocyte sugar transport by an effect, at least in part, directed at the brush-border membrane. The mechanisms responsible for these effects of pancreatic glucagon on brush-border sugar uptake are unknown.…”

“…Together with other recent observations of direct modulation of enterocyte sugar transport under a variety of conditions (Dempster & Kellett, 1992;Pennington et al 1992; (1966). The effect of intra-arterial insulin and glucagon on glucose metabolism of the small intestine in the dog.…”

The effects of insulin on glucose and fluid transport in the isolated small intestine of normal rats

“…Involvement of hepatoentral nerves in the signaling chain of insulin in the control of glucose absorption is proposed (Stupmel et al, 1996). Also it has been shown that glucose transport in small intestine is altered in response to humoral changes of glucagon (Debnam and Sharp, 1993) glucagons like peptide 2 (Drucker, 2002 ), insulin like growth factor (Castilla-Cortazar et al, 1999) and somatostatin (Fery et al, 2005) or paracrine elements such as prostaglandin E2 (Dempester and Kellett, 1992a) or bradykinin (Dempester and Kellett, 1992b). Although the results of the present study cannot completely rule out the involvement of paracrine elements or the enteric nervous system, but since the study was performed in vitro, one can conclude that the reported effect of the study is not dependent on any extra intestinal mechanism.…”