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T Goda

Publications and source records attributed to T Goda.

At least 109 records · Page 6Linked to original sources

Chronic effects of an alpha-glucosidase inhibitor (Bay o 1248) on intestinal disaccharidase activity in normal and diabetic mice.

Bay o 1248 is a potent alpha-glycosidase inhibitor that reduces postprandial hyperglycemia when administered p.o. with sucrose or maltose. The compound binds to and competitively inhibits the alpha-disaccharidases and is also readily absorbed across the intestinal mucosa. To evaluate its effect on the activity of disaccharidases and on metabolic control, groups of obese diabetic mice (C57BLKsJ db/db) were given the drug for periods of 3, 7 and 84 days as a drug food mixture (5 or 10 mg/100 g of food). Nondiabetic mice of the same strain were dosed for 3 and 7 days. The drug did not influence body growth, food intake or fasting blood glucose. However, urine glucose excretion was significantly decreased at the higher dose in the diabetic mice. The drug had no effect on the protein content of jejunum (proximal and middle thirds) or ileum (distal third) of the small intestine. The activity of sucrase and maltase was significantly decreased in practically all segments of the small intestine in both diabetic and nondiabetic mice. These changes were evident after 3 days of drug administration. Lactase was not affected by the drug. The mechanism underlying these changes, although unclear, is of significant interest and deserves further investigation.

1-Deoxynojirimycin↗

Effect of a high-dextrose diet on sucrase and lactase activity in jejunum of obese mice (C57BL/6J obob).

The activities of intestinal disaccharidases are known to be responsive to changes in the dietary intake of carbohydrates in the adult rat. Little is known, however, regarding the activities of these enzymes in obese subjects and how they are affected by differing carbohydrate intakes. To evaluate the effect of carbohydrate intake on the activity of intestinal disaccharidases in obesity, we used the genetically obese mouse C57BL/6J obob as an experimental model. Representing an example of early-onset obesity and mature-onset diabetes, this animal is characteristically hyperinsulinemic and hyperglycemic. Groups of obese mice and lean littermates were fed for 7 weeks equal amounts of either high-dextrose or low-dextrose isoenergetic diets. Sucrase, maltase, and lactase activities were measured on intestinal homogenates from the proximal and middle portions of the jejunoileum (upper and lower jejunum). Results were expressed as activity per tissue protein as well as total activity. Obese mice were found to have consistently greater total activity of both sucrase and maltase than their lean littermates, mostly as a result of increased intestinal size. Total lactase activity, however, was similar in the upper jejunum in both obese and lean mice, largely related to a decreased specific activity in obese mice. All mice fed the high-dextrose diet had significantly increased total activity of all disaccharidases studied when compared to the low-dextrose-fed animals, except for the lactase activity in the lower jejunum, where no differences were found in either group. Increases in activity related to high carbohydrate intake were a result of increases in specific activity.

Animals↗

Dietary regulation of intestinal glucohydrolases in adult rats: comparison of the effect of solid and liquid diets containing glucose polymers, starch, or sucrose.

For 1 wk, 3-mo-old male rats were fed a low-starch (5 cal%), high-fat (73 cal%, corn oil) diet followed by a high-glucose-polymer (70 cal%), low-fat (7 cal%, corn oil) or a middle-glucose-polymer (40 cal%), middle-fat (37 cal%, corn oil) diet. Other animals were fed similar diets but with starch or sucrose instead of the glucose polymers. Rats were sacrificed 2 or 7 days later. Food intake, body weight changes, and protein content per intestinal segment were similar in all groups. Increased carbohydrate intake evoked an increase of sucrase, maltase, glucoamylase, and lactase activity in both the jejunum and ileum. Effect of glucose polymers on glucohydrolase was similar in animals fed commercial liquid-soy-based infant formulas containing sucrose, glucose polymers, or both. Results support using glucose polymers as replacements for sucrose or starch when digestion impairment of those sugars is suspected or when a formula of lower osmolality is indicated.

Animals↗

Evidence of degradation process of sucrase-isomaltase in jejunum of adult rats.

To evaluate degradation processes of sucrase-isomaltase in adult rat jejunum, we determined enzymic activity of sucrase and isomaltase and compared it with the amount of immunoreactive sucrase-isomaltase. In rats fed or starved for 18h, killed at 10:00 h or 22:00 h, sucrase activity (expressed on the basis of total protein or of immunoreactive sucrase-isomaltase) was significantly (P less than 0.02) lower in the lower jejunum than in the upper jejunum; isomaltase activity was similar in both segments. Crossed immunoelectrophoresis demonstrated the existence of a second sucrase-isomaltase antigen reacting with anti-(sucrase-isomaltase) serum. This antigen was present in larger amounts in the lower jejunum than in the upper jejunum, exhibited immunological partial identity with the intact sucrase-isomaltase, and had isomaltase activity but no sucrase activity. Results suggest that this antigen is a degradation product of sucrase-isomaltase in which the sucrase active site has been broken down. To examine the role of pancreatic enzymes in degradation of sucrase-isomaltase, common pancreatico-biliary ducts were ligated. Within 18 h after the operation, the difference of sucrase activity between the upper and the lower jejunum disappeared and the amount of the second sucrase-isomaltase antigen markedly decreased in the lower jejunum. Our results indicate that, during the degradation of intestinal sucrase-isomaltase by the pancreatic proteinases, degradation of the sucrase active site precedes that of the isomaltase active site.

Animals↗

Precocious increase of sucrase activity by carbohydrates in the small intestine of suckling rats. I. Significance of the stress effect of sugar-induced diarrhea.

In this paper, we analyze the factors involved in the precocious increase of sucrase activity evoked by the early feeding of sucrose in suckling rats, and particularly, the role of diarrhea and stress in this phenomenon. Ten-day-old rats were removed from their mothers and gavage fed for 4 days at 3-h intervals either a basic low carbohydrate milk formula (10.8% fat, 8% protein, 1.4% carbohydrate; all by weight/volume) or basic low carbohydrate milk with: lactose (13%), fructose (13%), or Polycose (2%, 6%, or 13%); all formulas were isocaloric. Feeding the formula containing fructose or high (13%) Polycose led to diarrhea and evoked a concurrent increase of small intestinal sucrase activity. In further experiments, 11-day-old rats were fed the basic formula, the lactose (13%), the fructose (13%), and a sucrose (13%) formula for 8 h between 2 a.m. and 10 a.m. Also, 10-day-old rats were fed 0.5 ml of a solution of 5% mannitol in water while nursing with their mothers. The serum corticosterone levels were substantially increased within 8 h after the initiation of feedings with sucrose and fructose milks and the mannitol solution. The mannitol-fed rats also developed diarrhea within a day in association with a marked increase in sucrase activity. We conclude that a precocious increase of sucrase activity in the small intestine of suckling rats by dietary sugars is not caused by substrate induction, but is mainly due to the effect of stress. The stress is caused by diarrhea which is evoked by the feeding of indigestible and/or unabsorbable amounts of sugar.

Age Factors↗

Precocious increase of sucrase activity by carbohydrates in the small intestine of suckling rats. II. Role of digestibility of sugars, osmolality, and stomach evacuation in producing diarrhea.

The mechanisms of carbohydrate-induced diarrhea in suckling rats were investigated with respect to osmolality and type of sugar in the milk. Groups of 12-day-old rats were gavage fed either a basic low carbohydrate milk formula [10.8% fat; 8% protein; 1.4% carbohydrate (weight/volume)] or basic formula with added sucrose, fructose, lactose, or glucose polymers, all as 13% (weight/ volume). All formulas were isocaloric. Their corresponding osmolalities were 278, 645, 1,130, 617, and 349 mOsmol/kg, respectively. Gastric evacuation of water-soluble materials from formulas containing sucrose, fructose, or glucose polymers was significantly slower than the gastric evacuation of the basic formula and the formula that contained lactose. The net fluid absorption from the small intestine was significantly greater from the basic and lactose-containing formulas when compared with sucrose, fructose, or glucose polymer-containing formulas. When the synthetic milk formulas were placed directly into the isolated jejunoileum in vivo, the formulas of higher osmolality (fructose, sucrose, and lactose) caused water flux into the intestine at 60 min, while digestion of the lactose formula reversed the water flux within 120 min. We conclude that the type of added sugar is a decisive factor in gastric evacuation, and that water flux into and out of the intestine is significantly affected by the osmolality and rate of digestion and absorption of the carbohydrate in the formula; these differences among sugars may play a significant role in the etiology of diarrhea.

Animals↗

Dietary regulation of intestinal lactase and sucrase in adult rats: quantitative comparison of effect of lactose and sucrose.

To characterize the mechanisms leading to dietary evoked increases of lactase and sucrase activities by carbohydrates, we performed a quantitative comparison of the effects of lactose and sucrose on the corresponding disaccharidases in the jejunum of 2-month-old rats. For 7-10 days the rats were fed a low-starch (5 cal%), high-fat (73 cal%) diet, and for various periods of time (3-72 h) were given an isocaloric sucrose or lactose (20, 40, or 70 cal%) diet. Lactase and sucrase activities in jejunal homogenates were significantly increased within 3 h after the initial feeding of the sucrose (40 cal%) diet. After 3 h of feeding the sucrose diet, sucrase activity gradually increased and reached its maximum at 24 h, whereas lactase activity did not exhibit further change. Increased intake of sucrose led to an increase of lactase and sucrase activity. Within a range of doses of digestible amounts of lactose, the effect of diet containing lactose on these disaccharidase activities was similar to the effect of the diet containing sucrose. This similarity suggests the important role of the common constituent sugar, i.e., glucose. Further, analyses of response to these disaccharides along the villus-crypt axis revealed that the increase of lactase activity occurs at a more apical and broader locus of cohort of epithelial cells along the height of the villus than that of sucrase, suggesting that different mechanisms are involved in dietary regulation of lactase and sucrase.

Animals↗

Relation between dietary-induced increase of intestinal lactase activity and lactose digestion and absorption in adult rats.

To study the relation between dietary-induced increase of intestinal lactase activity and lactose absorption, 11-wk-old rats were fed either a high-starch (70 cal%), low-fat (7 cal%) diet or a low-starch (5 cal%), high-fat (73 cal%) diet for 7 days. Food intake and body weight changes were similar in the two dietary groups. In the first experiment, lactose absorption was studied in vivo after oral administration of 600 mg lactose (10% solution in water with added [3H]PEG) to rats fasted for 16 h. Groups of rats were killed at time 0 and at 1-h intervals for the next 3 h. Lactase activity and lactose absorption were significantly higher (P less than 0.01) in the high-starch group than in the low-starch group. In the subsequent experiment, 9-wk-old rats were fed the two isocaloric diets for 3 days. By use of the everted sac technique, we have demonstrated a significantly higher absorption of monosaccharides from lactose in the high-starch diet group; also, glucose transport was higher in the high-starch diet-fed animals. When Tris, an inhibitor of lactase, was added into the mucosal fluid, absorption of lactose was abolished and no effect was seen on glucose absorption (in vivo and in vitro). In both experiments, significant linear regression was established between lactase activity and lactose absorption. Our results thus show that the increase in lactase activity, induced by feeding a high-starch diet to adult rats, is accompanied by an increased capacity to hydrolyze lactose and absorb the constituent monosaccharides.

Absorption↗

Different effect of starvation on activity of sucrase and lactase in rat jejunoileum.

Activities of lactase and sucrase were determined in proximal, middle, and distal thirds of the jejunoileum of 15-wk-old male rats starved for 1, 2, and 3 days and in rats fed a high-sucrose diet for 24 h after 3 days of starvation. Sucrase activity (expressed per tissue protein or DNA as well as per intestinal segment) showed a progressive decrease during starvation in proximal and middle segments but not in the distal segment. Lactase activity expressed per tissue protein or DNA in all segments increased significantly. This was obviously due to the loss of tissue protein and DNA because total lactase activity per segment did not change. Refeeding the sucrose diet produced an increase of sucrase activity without influencing lactase activity. In serial tissue homogenate of jejunal villus-crypt columns prepared using cryostat sectioning, it was shown that, during starvation, activity of lactase (specific and total) increased in the upper and middle villus. Sucrase activity (specific and total) during starvation decreased and after refeeding increased in the lower and middle villus.

Animals↗

Dietary-induced rapid decrease of microvillar carbohydrase activity in rat jejunoileum.

Activities of several carbohydrases and peptidases were determined in proximal, middle, and distal thirds of the jejunoileum of female 16-wk-old rats that were fed a high-starch (70 cal%), low-fat (7 cal%) diet for 2 wk and also in rats that (after this introductory period) were fed an isocaloric low-starch (5 cal%), high-fat (73 cal%) diet for 1, 2, and 3 days. The body weight changes, food intake, amount of protein per intestinal segment, and rate of enterocyte migration were practically the same in all groups during these experimental periods. The decreased intake of starch was followed by a rapid decrease (40-80%) of carbohydrases (lactase, sucrase, maltase, and glucoamylase) within the first 24 h in total intestinal homogenates--and as studied in cryostat serial sections--in all regions of the jejunal villus-crypt columns, and mainly in proximal and middle segments. In contrast, the activities of leucylnaphthylamidase and L-phenylalanylglycine hydrolase exhibited little change except for a slight temporary decrease of activity on the 1st day in the proximal segment only (25-30%). Thus these data show that a decrease of starch content in an isocaloric diet evokes a rapid decrease in the activity of microvillar carbohydrases and that activity of these enzymes both in mature and immature enterocytes is capable of reacting to a change (decrease) of dietary carbohydrate content.

Animals↗

Changes of the activity and content of sucrase-isomaltase complex in the intestinal mucosa during the development of streptozotocin-induced diabetes in rats.

The changes in the activity and content of sucrase-isomaltase complex (S-I) in the intestinal mucosa were studied during the development of diabetes induced by streptozotocin in rats. On days 0, 1, 3, 5, and 10 after an intraperitoneal injection of streptozotocin (70 mg/kg), the enzyme activity and the enzyme content were observed in the jejunum and ileum. Sucrase and isomaltase activities markedly increased from the 3rd day both in the jejunum and ileum, and kept increasing till the 10th day especially in the ileum. The enzyme content of S-I also increased in parallel with its activity during the development of diabetes. However, in the early stage of diabetes, sucrase activity per microgram of S-I content increased both in the jejunum and ileum. Isomaltase activity per microgram of S-I content increased temporarily in the ileum. These results suggest that the increase of disaccharidase activities in the early stage of diabetes induced by streptozotocin is not only due to the increase of the enzyme content, but also due to the change of the enzyme catalytic property.

Animals↗