Hormonal regulation of canine intestinal cholesterol synthesis.
Hormonal regulation of intestinal cholesterol synthesis was studied both in vitro and in vivo. Cholesterol synthesis rate was determined by measurement of 3-hydroxy-3-methylglutaryl-coenzyme A reductase (EC 1.1.1.34) activity and by incorporation [14C]acetate into sterol. In vitro studies utilized organ culture of canine ileal mucosa. During 6-h culture, reductase activity was stimulated sevenfold. Insulin (10-6 M) augmented this rise to 144 +/- 7% of th control activity, while 10(-8) M glucagon, 10(-3) M adenosine 3',5'-cyclic monophosphate, and 3-isobutyl-1-methylxanthine suppressed activity (final reductase activity was 83 +/- 3%, 75 +/- 4%, and 41 +/- 3%, respectively, of cultured control values). In vivo studies utilized dogs with isolated Thiry-Vella ileal fistulas. In vivo, insulin doubled reductase activity while glucagon led to a 42 +/- 9% suppression. It is concluded that insulin and glucagon may be potential physiological regulators of intestinal cholesterol synthesis. The glucagon effect may be mediated by cyclic nucleotides.
D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D004285:Dogs; D005934:Glucagon / Q000494:pharmacology*; D006903:Hydroxymethylglutaryl CoA Reductases / Q000378:metabolism*; D007082:Ileum / Q000201:enzymology; D066298:In Vitro Techniques; D007328:Insulin / Q000494:pharmacology*; D007413:Intestinal Mucosa / Q000201:enzymology*; D013393:Sucrase / Q000378:metabolism
D007328:Insulin; D005934:Glucagon; D006903:Hydroxymethylglutaryl CoA Reductases; D000469:Alkaline Phosphatase; D013393:Sucrase