The effects of a high-galactose diet on intestinal adaptation and enteroglucagon levels in rats
Haskins, Chad Allen
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Enteroglucagon (EG) consists of two hormones(glicentin and oxyntomodulin) and is co-secreted with glucagon-hke peptide-1 and -2 fi-om the intestinal L-cell after posttranscriptional processing of the proglucagon prohormone. EG has long been proposed as a mediator of intestinal adaptation leading to increased nutrient uptake rates. The current study investigated several hypotheses. First, feeding a poorly metabolized 55 % galactose diet ad libitum would lead to both specific (changes in the transport rate of a single nutrient by upregulation of its transporter) and non-specific (intestinal growth or changes in membrane potential across an enterocyte that affects the transport rate of aU nutrients)modes of intestinal adaptation. Second, pair-feeding the 55 % galactose diet to control intake values would elicit only the specific mode of adaptation. Third, increased plasma EG levels would correlate with changes in nutrient uptake rates. I measured intestinal growth as well as glucose, alanine and proline uptake rates across the brush-border membrane to examine the mode of adaptation in rats on the different diets for 1, 2, 4 or 7 days. To determine what role glucagon and EG play in this process, plasma samples were collected and the plasma levels of glucagon and EG were quantified using a subtraction radioimmunoassay. In doing so, a new EG antibody (9362) was characterized. Rats fed the galactose diet ad libitum demonstrated significant intestinal growth and significant increases in glucose uptake (mdicating specific and non-specific adaptation), while pair-fed rats showed the significant increases in glucose transport rates without changes in intestinal dimensions (specific only). Both sets showed down-regulation of alanine and proline transport rates compared to carb-free controls. However, ad libitum rats showed higher transport rates than those of pair-fed rats likely due to non-specific adaptatioa No significant difference was detected for EG between different animals, but a slight increase across time was observed in pair-fed rats and a larger increase occurred in ad libitum rats, with the highest levels attained on day 4 in both groups. Glucagon showed significant increases time in the ad libitum rats, but not the pair-fed rats. This study suggests that different diets and feeding modes may elicit different patterns of EG secretion. Nevertheless, more investigation is needed to further elucidate the exact role EG plays in the different modes of adaptation.