Intestinal enzymes: indicators of proliferation and differentiation in the jejunum.

Some intestinal enZymes were assayed which were related to: (i) Cellular proliferation, for example, aspartate carbamoyltransferase, thymidine kinase, uridine kinase, and dihydroorotase; (ii) cellular differentiation, for example, lactase, invertase, maltase, alkaline phosphatase, and dipeptidase; and (iii) lysosomes, for example, beta-glucuronidase, acid beta-galactosidase, and acid phosphatase. These enzymatic determinations can be used to distinguish the crypt from the villus during healthy or diseased states.

Effect of carbohydrate and corticosteroids on activity of -glucosidases in intestine of the infant rat.

The activities of intestinal sucrase and isomaltase are not detectable in rats before 15-16 days of age, but administration of corticosteroids precociously induces the activities of these two alpha-glucosidases. 9-day old rats were removed from their mothers, warmed in an incubator, and fed by constant infusion through gastrostomies. The basic diet was a soya preparation to which various sugars were added. When the diet contained 2% sucrose, diarrhea ensued for 48 hr, but subsided when intestinal sucrase and isomaltase appeared precociously. In animals fed sucrose, the activities of sucrase and isomaltase were markedly increased as compared to animals on carbohydrate-free diets (sucrase 2.41+/-0.23 vs. 0.63+/-0.13 U, isomaltase 3.43+/-0.42 vs. 0.78+/-0.18 U). Maltase activity was doubled, while lactase was not altered significantly. The mitotic index of crypt cells, the depth of crypts, and incorporation of thymidine-(3)H into DNA were increased. In adrenalectomized rats, activities of sucrase and isomaltase were not detected nor induced by sucrose. Steroids given to adrenalectomized rats caused appearance of the enzymes; but if cortisone and sucrose were given together, there was synergism evidenced by a marked increase in activities (sucrase 7.2+/-1.1 vs. 0.68+/-0.12 U). In contrast to observations in adult animals, the effect of sucrose on alpha-glucosidases in developing animals demands the participation of the adrenal gland.

Effect of colchicine on intestinal disaccharidases: correlation with biochemical aspects of cellular renewal.

There was a significant depression of the activities of intestinal lactase, invertase, and alkaline phosphatase in rats given drinking water containing 2.5 mg of colchicine per 100 ml. Activities of intestinal maltase, aspartate transcarbamylase, and dihydroorotase were not affected by the drug. Injection of colchicine (1 mg/kg) caused depression of intestinal invertase activity within 8 hr. Investigation of the effect of colchicine on the disaccharides in vitro demonstrated that invertase and maltase were not affected by concentrations up to 125 mg/100 ml. Intestinal lactase was inhibited by concentrations exceeding 5 mg/100 ml. Calculation of the concentration of colchicine present in the intestine, after a single injection, indicated that the in vivo effect of colchicine was not due to simple enzyme inhibition. Histological examination showed an increase in crypt cells but no decrease in the length of the villi. Cellular migration along the villi, as well as activity of uridine kinase in intestinal mucosa, was increased in colchicine-treated rats. It was concluded that colchicine did not depress intestinal invertase, lactase, and alkaline phosphatase by decreasing cellular renewal, but rather it exerted its effect directly on the differentiated cells of the villus.

Alteration of human placental lactogen by mammary gland.

Human placental lactogen was prepared in high purity and in good yield applying a minimum of purification steps. The isolated hormone was characterized with respect to isoelectric and electrophoretic properties, molecular size (estimated mol. wt. 23 000) and stability to heat, pH and organic solvents. Investigation of in vitro interaction between placental lactogen and mammary gland (mouse, rat) revealed a rapid alteration of hormone with loss of immunoreactivity resulting. The target organ as a selective alteration site of placental lactogen was suggested by a lack of similar action on the hormone by a number of other tissues tested, including liver, kidney and lung. The reaction involving hormone alteration by mammary gland was localized to a particulate-bound enzyme, sedimentable at 10 000 X g and undissociated by sonication in 0.5% Triton X-100. Examination of the reaction products revealed hormone degradation with formation of diffusible components and loss of original electrophoretic identity as well as immunoreactive properties. The reaction characteristics included: pH optimum between 7.5 and 8.0, an absolute salt requirement (NaCl, KCl, at concentration greater than 0.15 M for maximal activation), inhibition by Cleland's reagent and lack of reaction interference by pituitary prolactin.

Risk factors for diabetes and cardiovascular disease in young Australian aborigines. A 5-year follow-up study.

OBJECTIVE: To test the hypothesis that hyperinsulinemia and glucose intolerance are present at an early age in australian aborigines and can be used to predict the eventual development of NIDDM. RESEARCH DESIGN AND METHODS: Baseline anthropometric, pubertal stage, and blood pressure data were collected for 100 Australian aboriginal children and adolescents in 1989. Plasma concentrations of glucose, insulin, C-peptide, triglycerides, and LDL, HDL, and total cholesterol were measured before and during an oral glucose tolerance test. All measurements were repeated in 74 individuals from the original study population in 1994. Results were compared among hyperinsulinemic and normoinsulinemic subjects, and subjects with normal or abnormal glucose tolerance. RESULTS: The percentage of subjects who were overweight increased from 2.7% at baseline to 17.6% 5 years later. At a mean age of 18.5 years, 8.1% of the population had impaired glucose tolerance (IGT), 2.7% had diabetes, and 21.6% had elevated cholesterol concentrations in plasma. Dyslipidemia was particularly prevalent among male subjects in the population: 34.4% had elevated plasma cholesterol and 21.9% had elevated LDL cholesterol values. Of the eight subjects who had diabetes or IGT in 1994, four were classified as hyperinsulinemic in 1989 and four were not. CONCLUSIONS: The major finding of this study is the high prevalence of risk factors for NIDDM and cardiovascular disease in this population of aboriginal children and adolescents. Abnormalities of carbohydrate and lipid metabolism were well established by late in the second decade of life. Although many subjects had high insulin levels and there was evidence of insulin resistance in the population, hyperinsulinemia did not predict the development of abnormal glucose tolerance 5 years later.

The role of nutrition in the development of normal cognition.

The goal of this section of the meeting was to review the relation between nutrition and cognition. The topics selected for discussion included generalized malnutrition, iodine deficiency, iron metabolism, and the relation of fatty acids to the development of the nervous system. Each subject is immense and demands a detailed exposition, but can be treated here only in brief form. However, these short essays should give some insight into the status of our current knowledge.

Fructose absorption.

Fructose found in modern diets as a constituent of the disaccharide sucrose is absorbed by a well-characterized absorptive system integrating enzymatic hydrolysis of the disaccharide and transfer of the resulting two monosaccharides through the apical membrane of the epithelial cell. The increasing use of high-fructose syrups and crystalline fructose prompted new studies aimed at the determination of the absorptive capacity for free fructose in the human gut. Results indicate that the capacity for fructose absorption is small compared with that for sucrose and glucose and is much less than previously estimated. The unexpected finding that the simultaneous ingestion of glucose can prevent fructose malabsorption suggests that the pair of monosaccharides might be absorbed by the disaccharidase-related transport system as if they were the product of the enzymatic hydrolysis of sucrose. This absorptive mechanism might not be able to transport fructose when ingested without glucose.

The effect of exercise on fructose absorption.

The effect of exercise on intestinal absorption of fructose was evaluated in 10 subjects after they consumed four beverages, each containing a total of 50 g carbohydrate: 100% fructose (100F), 95% fructose and 5% glucose (95F), 70% fructose and 30% glucose (70F), and 100% glucose (100G), as well as a water placebo. With 100F and 95F, breath hydrogen, which is an index of incomplete absorption, increased significantly in all subjects. In contrast, hydrogen excretion did not increase in any subject after consumption of 100G or water, or in five of seven subjects who consumed 70F. The rapid increase in hydrogen excretion observed when consumption of 100F was followed by exercise was not noted during a comparable nonexercise trial. These data suggest that intestinal capacity for absorption of fructose is readily saturated after ingestion of amounts as small as 50 g and that exercise, which reduces intestinal transit time, can cause incomplete absorption of fructose.

Lactose malabsorption among adult Indians of the Great Basin and American Southwest.

The prevalence of primary adult lactose malabsorption and the pattern of milk use were studied among 109 Indians from various tribes of the American Great Basin and Southwest. Included were 100 persons who reported being full-blooded Indians as well as three with Mexican admixture and 6 with some European ancestry. Lactose malabsorption was found in 92% of the full-blooded Indians but in only 50% Indians who acknowledged European admixture. These results agree with those of studies of native Americans done elsewhere which show very high prevalences of such lactose malabsorption among adults reported as fullblooded and lower prevalences among individuals with admitted European ancestors. The suggestion made is that in pre-Colombian times, before interbreeding with Europeans began on any scale, such lactose malabsorption may have been nearly universal among native American adults. Most of the Indians studied consumed abundant milk since childhood but were nevertheless predominantly malabsorbers as adults. This argues against the induction hypothesis advanced by some to explain the striking ethnic differences that occur around the world in primary adult lactose malabsorption.

Growth of immigrant children in the newcomer schools of San Francisco.

A semilongitudinal study on growth and development was initiated on immigrant and refugee school-aged children in San Francisco. Anthropometric values (height, weight, arm circumference, and triceps and subscapular skinfolds) were collected soon after their arrival in the United States and repeated at 3-month intervals for 1 year. Data were analyzed by age-gender cohorts. z Score calculations for measures of height-for-age, weight-for-age, and weight-for-height demonstrated a significant overall deficiency in height-for-age and weight-for-age at the time of the first measurement. Comparisons with a US standard indicated that most of the children were between the fifth and 25th percentiles in these measures. There were fewer children who were significantly deficient in weight-for-height. Calculations for median growth rate indicated that most cohorts exhibited a median growth velocity that was close to or exceeded the median for US white children. There was also significant improvement in weight-for-age. The results indicated that these immigrant and refugee children accelerated their growth markedly in an optimum nutritional environment and were in a period of catch-up growth.

Relationships between glucose metabolism and thermogenesis with and without prior exercise in obese women with non-insulin-dependent diabetes mellitus.

The rate of insulin-stimulated glucose disposal is reduced in individuals with insulin resistance, and is associated with a blunted or absent increase in energy expenditure in response to a glucose load. The magnitude of the effect of glucose on energy expenditure (EGEE) may be a function of opposing changes in the rate of glucose disposal (Rd) and hepatic glucose production (HGP). In this study, six women with non-insulin-dependent diabetes mellitus (NIDDM) were studied on a metabolic ward in each of three conditions. On days 1 and 2, they did no exercise (NX) or else performed low-intensity exercise ([LO] 3,118 kJ [745 kcal]) at 50% maximal oxygen consumption [V0(2)max]) or high-intensity exercise ([HI] 3,114 kJ [744 kcal] at 75% V0(2)max). On day 3, infusion of 6,6(2)H-glucose in the basal state was immediately followed by infusion of glucose, 6,6(2)H-glucose, and insulin at fixed rates. Indirect calorimetry was performed during the last 30 minutes of each infusion. EGEE was not different among the three conditions (mean +/- SEM: NX -0.18 +/- 0.11, LO -0.08 +/- 0.05, and HI -0.08 +/- 0.07 kJ/min) and was inversely related to steady-state plasma glucose concentration, a direct measure of insulin resistance (r = -.89, P < .05). EGEE was positively correlated with glucose Rd (r = .94, P < .001) and negatively correlated with HGP (r = -.91, P < .05). The data indicate that the glucose effect on energy expenditure was slightly positive in the more insulin-sensitive individuals, but negative in the more insulin-resistant subjects. The EGEE appears to be determined by the relative balance between energy required to store glucose and energy saved by suppression of glucose production.

Unusual high-density lipoprotein subclass distribution during late pregnancy.

Plasma lipoprotein distribution during late pregnancy is unusual since high-density lipoprotein (HDL) levels are increased in the presence of hypertriglyceridemia; the latter is usually associated with decreases in HDL levels. To determine whether there is a relationship between late-pregnancy lipid levels and specific HDL subclasses, HDL size distribution was determined by nondenaturing gradient gel electrophoresis (GGE) in a group of 36 women at 35 to 36 weeks of gestation and again at 6 weeks' postpartum, and in a group of 10 nonpregnant women. At 35 to 36 weeks of gestation, plasma triglyceride (TG) and cholesterol concentrations were significantly increased over postpartum levels (218 +/- 62 v 112 +/- 69 mg/dL and 234 +/- 48 v 197 +/- 36 mg/dL, respectively). During late pregnancy, apolipoprotein A-I (apo A-I) and HDL cholesterol concentrations were also increased relative to postpartum levels (211 +/- 42 v 168 +/- 20 mg/dL and 63 +/- 13 v 53 +/- 11 mg/dL, respectively). GGE analysis indicated that at 35 to 36 weeks of gestation, 86% of the subjects had a substantial increase of the most buoyant and largest of the HDL species, HDL2b; postpartum and nonpregnant HDL subclass distribution was characterized by the predominance of HDL3a, which are smaller, more dense HDL. The shift in the HDL subclass distribution during late pregnancy was associated with significant positive correlations between HDL2b and apo A-I (r = .50, P < .05) and HDL cholesterol (r = .60, P < .001). There were significant elevations in the concentrations of cholesteryl ester transfer protein (CETP) and estrogen during late pregnancy.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of exercise intensity on insulin sensitivity in women with non-insulin-dependent diabetes mellitus.

Exercise enhances insulin sensitivity in people with non-insulin-dependent diabetes mellitus (NIDDM), but the intensity of exercise necessary to optimize the effect is unknown. Eight women with NIDDM were studied on a metabolic ward in each of three conditions: 1) low-intensity exercise (LO) that consisted of treadmill walking at 50% of maximal O2 consumption on days 1 and 2, 2) high-intensity exercise (HI) that consisted of walking at 75% of maximal O2 consumption, and 3) no exercise (NX). The duration of exercise was adjusted so that energy expenditure was equal in both exercise conditions. On day 3, glucose, [6,6-2H]glucose, and insulin were infused at fixed rates for 3 h. Insulin sensitivity was determined both by steady-state plasma glucose concentration and rate of glucose disposal per unit plasma insulin. Steady-state plasma glucose concentration and rate of glucose disposal per unit plasma insulin were almost identical after LO or HI; values were significantly greater than after NX. Plasma glucose response to a test meal was the same among the three conditions, but plasma insulin response was lower for HI and LO compared with NX. We conclude that under these conditions LO is as effective as HI in enhancing insulin sensitivity in people with NIDDM.

Influence of maternal body habitus and glucose tolerance on birth weight.

Many physicians believe that macrosomia is a hallmark of a pregnancy complicated by glucose intolerance. Because the prevalence of obesity is increased among women with gestational diabetes, fetal overgrowth may be attributable at least in part to maternal obesity. We studied 2069 black, Latina, Chinese, and white mother-infant pairs to determine the interaction between maternal body habitus, maternal glucose homeostasis, and certain indices of fetal growth. Chinese women had a significantly higher serum glucose 1 hour after administration of 50 g glucose (136.6 +/- 32.7 mg/dL) than any of the other three ethnic groups. Black women had a significantly lower value for glucose (114.8 +/- 28.2 mg/dL) than either Chinese or Latina women (124.9 +/- 31.4 mg/dL). Results for Latina and white women (121.5 +/- 26.2 mg/dL) were not significantly different. Body mass index (BMI) was used to classify the subjects. The regression coefficient for the entire sample indicated a modest association of glucose with increased birth weight when maternal BMI was controlled. The BMI of the Chinese infants had a significant association with higher concentrations of glucose after administration of 50 g glucose. Maternal body habitus should be considered a major confounder in studies of the relationship of maternal glucose tolerance and infant birth weight.

Carbohydrate malabsorption.

Carbohydrate malabsorption is a very important clinical entity, particularly in pediatrics, where, if untreated, it can lead to malnutrition and failure to thrive. Malabsorption that can be treated readily with elimination of the offending carbohydrate. Knowledge by the physician of the specific mechanisms involved in the physiology of carbohydrate absorption and digestion will help in the handling of the clinical situation of malabsorption.