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Renin-angiotensin system in phlorhizin compared with alloxan diabetes in the rat.

In alloxan-treated diabetic rats, plasma renin activity (PRA) is decreased. One possible mechanism that may explain the decreased PRA is an increased delivery of sodium to the macula densa produced by the glucose osmotic diuresis, resulting in decreased renin release. To evaluate this possible mechanism, rats with phlorhizin diabetes, which produces a glucose osmotic diuresis without hyperglycemia, were studied and compared with rats with alloxan-induced diabetes. Whereas phlorhizin-treated rats had low blood glucose and alloxan-treated rats had elevated glucose, the glucose osmotic diuresis was similar in the two groups. PRA and plasma renin concentration (PRC) were significantly increased in the phlorhizin group. In the alloxan group, PRA was decreased and angiotensin II sensitivity increased, both significantly. Plasma renin substrate (PRS) remained adequate in each group. These results suggest that the decreased PRA in alloxan-induced diabetes is due neither to factors associated with the glucose osmotic diuresis including changes in renal tubular sodium not to decreased PRS.

Alloxan↗

Effect of dietary niacin supplementation on phlorhizin and 1,3-butanediol-induced ketonemia and hypoglycemia in steers.

1,3-Butanediol and phlorhizin were used to induce ketonemia and hypoglycemia in steers. Oral administration of butanediol increased blood beta-hydroxybutyrate (BHB) and plasma nonesterified fatty acids (NEFA) and decreased serum glucose. Subcutaneous injections of phlorhizin, given in addition to butanediol orally, further increased NEFA and BHB concentrations and decreased glucose. Dietary niacin supplementation of steers given phlorhizin and butanediol caused serum glucose concentration to increase and blood BHB and plasma NEFA concentrations to decrease.

3-Hydroxybutyric Acid↗

The inhibitory effect of phlorhizin and phloretin on hexose transport in the liver.

The inhibitory effect of phlorhzin on renal tubular glucose absorption has been known for a long time now. But its aglycone, phloretin is almost completely devoid of such an action in the kidney although it is more active than phlorhzin on sugar transport mechanism in human erythrocytes. The present investigation was designed to find out the effects of these two chemically related substances on hexose transport in the liver. The effect of 1mM phlorhzin or ImM phloretin on the transport of D-stereoisomers of glucose, galactose and fructose using the first pass extraction technique. It was found that phloretin was a better inhibitor of hexose transport in the liver. The difference between the effect of phlorhizin, and the phloretin was highly significant. The inhibitory pattern of the two chemical substances on the three hexoses indicate a discrimination between galactose transport and glucose or fructose transport in the liver.

Animals↗

Lactase phlorhizin hydrolase turnover in vivo in water-fed and colostrum-fed newborn pigs.

We have estimated the synthesis rates in vivo of precursor and brush-border (BB) polypeptides of lactase phlorhizin hydrolase (LPH) in newborn pigs fed with water or colostrum for 24h post partum. At the end of the feeding period, piglets were anaesthetized and infused intravenously for 3h with L-[4-3H]- phenylalanine. Blood and jejunal samples were collected at timed intervals. The precursor and BB forms of LPH were isolated from jejunal mucosa by immunoprecipitation followed by SDS/PAGE, and their specific radioactivity in Phe determined. The kinetics of precursor and BB LPH labelling were analysed by using a linear compartmental model. Immunoisolated LPH protein consisted of five polypeptides [high-mannose LPH precursor (proLPHh), complex glycosylated LPH precursor (proLPHe), intermediate complex glycosylated LPH precursor (proLPH1i) and two forms of BB LPH]. The fractional synthesis rate (Ks) of proLPHh and proLPHc (approx. 5%/min) were the same in the two groups but the absolute synthesis rate (in arbitrary units, min-1) of proLPHh in the colostrum-fed animals was twice that of the water-fed animals. The Ks values of proLPHi polypeptides were significantly different (water-fed, 3.89%/min; colostrum-fed, 1.6%/min), but the absolute synthesis rates did not differ. The Ks of BB LPH was not different between experimental treatment groups (on average 0.037%/min). However, the proportion of newly synthesized proLPHh processed to BB LPH was 48% lower in colostrum-fed than in water-fed animals. We conclude that in neonatal pigs, the ingestion of colostrum stimulates the synthesis of proLPHh but, at least temporarily, disrupts the processing of proLPH polypeptides to the BB enzyme.

Amino Acid Sequence↗