Effects of hypothyroidism on glucose and glutamine metabolism by the gut of the rat

Abstract

1. The metabolism of glucose and glutamine was studied in the small intestine and the colon of rats after 4–5 weeks of hypothyroidism. 2. Hypothyroidism resulted in increases in the plasma concentrations of ketone bodies (P < 0.05), cholesterol (P < 0.001) and urea (P < 0.001), but decreases in the plasma concentrations of free fatty acids (P < 0.05) and triacylglycerol (P < 0.001). These changes were associated with decreases in the plasma concentrations of total triiodothyronine, free tri-iodothyronine, total thyroxine and free thyroxine. 3. Hypothyroidism decreased both the DNA content (by 30.5%) and the protein content (by 23.6%) of intestinal mucosa, with the protein/DNA ratio remaining unchanged. The villi in the jejunum were shorter (P < 0.05) and the crypt depth was decreased by about 26.5% in hypothyroid rats. 4. Portal-drained visceral blood flow showed no marked change in response to hypothyroidism, but was accompanied by decreased rates of extraction of glucose, lactate and glutamine and release of glutamate, alanine and ammonia. 5. Enterocytes and colonocytes isolated from hypothyroid rats showed decreased rates of utilization and metabolism of glucose and glutamine. 6. The maximal activities of hexokinase (EC 2.7.1.1), 6-phosphofructokinase (EC 2.7.1.11), pyruvate kinase (EC 2.7.1.40), citrate synthase (EC 4.1.3.28), oxoglutarate dehydrogenase (EC 1.2.4.2) and phosphate-dependent glutaminase (EC 3.5.1.2) were decreased in intestinal mucosal scrapings from hypothyroid rats. Similar decreases were obtained in colonic mucosal scrapings (except for citrate synthase and oxoglutarate dehydrogenase) from hypothyroid rats. 7. It is concluded that hypothyroidism decreases the rates of utilization of glucose and glutamine (both in vivo and in vitro) by the epithelial cells of the small intestine and colon. This may be caused by changes in protein turnover and/or the maximal activities of key enzymes in the pathways of glucose and glutamine metabolism in these cells.