The effects of indigestible dextrin on sugar tolerance: I. Studies on digestion-absorption and sugar tolerance]

It is widely acknowledged that high viscosity water-soluble dietary fibers such as pectin and guar gum affect a lowering of blood glucose levels and a reducing of insulin secretion following a sugar load. However, as dietary fibers vary in origin and in chemical properties, their physiological functions differ as well. In this study the effects of Indigestible Dextrin (PF-C), a low viscosity, water-soluble dietary fiber obtained through acid and heat-treatment of potato starch, on various aspects of sugar tolerance were examined. First, the influence of PF-C on sucrose hydrolysis was examined in rat intestinal mucosa cell homogenate confirming that PF-C did not inhibit sucrase activity. Then, in order to investigate the influence of PF-C on sugar digestion-absorption, an experiment was performed by using the everted intestinal sac of the rat in vitro. PF-C did not have an effect on glucose-transport into the serosal medium, whereas PF-C did inhibit the transport of hydrolyzed-glucose from sucrose, with no change in the hydrolysis of sucrose. Recently, Crane et al. reported that there is a specific route for hydrolyzed glucose from sucrose in glucose-absorption on the enteric surface (disaccharidase related transport system). The possibility exists that PF-C specifically affects this pathway. Further, total glucagon released into the serosal medium stimulated by both glucose and sucrose were reduced by PF-C. On the basis of these results, an oral sugar tolerance test was conducted in both rats and healthy human subjects. In male Sprague-Dawley rats (8 weeks old, 250-280g) concurrent administration of PF-C (0.6g/kg body weight) reduced an increase in plasma insulin levels with no change in glucose levels following a glucose (1.5g/kg body weight) load. Further noted were reductions in increases in both plasma glucose and insulin levels following a sucrose (1.5g/kg body weight) plus PF-C (0.6g/kg body weight) load to that of the sucrose (1.5g/kg body weight) single load. These findings reflect the above mentioned in vitro results. Moreover, in healthy male subjects the increase in both plasma insulin and glucagon-like immunoreactivity (Gut GLI) levels following a Trelan-G75 load were significantly reduced by concurrent administration of PF-C. From these observations it would appear that the effectiveness of reducing insulin secretion by PF-C results due to the decrease in sugar absorption by inhibiting the disaccharidase-related transport system.(ABSTRACT TRUNCATED AT 400 WORDS)     

Effects of graded α-glucosidase inhibition on sugar absorptionin vivo

The effect of inhibition of disaccharidases on the degree of absorption of glucose, lactose, and sucrose was examined utilizing an in vivo model in the rat. Acarbose, a competitive alpha-glucosidase inhibitor was utilized to selectively inhibit small intestinal mucosal enzymes. Adult rats (250-350 g body weight) were the subjects of intraduodenal bolus infusion experiments with either sugar alone or sugar plus acarbose. All sugars were infused at a dose of 0.5 g/kg body weight. Portal venous blood glucose was determined at 30-min intervals from 0 to 150 min. Glucose (monosaccharide) and lactose (beta-galactoside) absorption were not altered by the presence of acarbose. In contrast, sucrose (alpha-glucosidase) absorption was significantly diminished in the presence of acarbose. Sucrose absorption in the presence of increasing acarbose doses (0.7-5.6 mg/kg body weight) was depressed in a dose-dependent fashion. Linear regression analysis revealed a high degree of correlation between residual sucrase activity and area under blood glucose curve (r = 0.9837). Similar degrees of correlation were found between acarbose dose and area under blood glucose curve (r = -0.9322), and between residual sucrase activity and acarbose dose (r = -0.9695). These data confirm that acarbose is a selective alpha-glucosidase inhibitor that does not affect monosaccharidase transport. In the presence of acarbose, alpha-glucosidase absorption is diminished in a dose-dependent fashion. Postprandial glucose rise following an alpha-glucosidase meal seems to be determined, in the presence of graded acarbose inhibition, by residual mucosal alpha-glucosidase activity.     

Hyperglycemia induces intestinal sucrase activity in subtotally pancreatectomized rats

The effects of experimental diabetes, hypertonic glucose infusion, and subsequent insulin administration on the sucrase activity of the small intestine were studied using intestinal segments completely excluded from luminal continuity by construction of Thiry-Vella fistulas in rats. Eight weeks after subtotal pancreatectomy, the rats contracted insulin-deficient diabetes mellitus, and sucrase activity was enhanced in both the Thiry-Vella loop and in the proximal jejunum in continuity. Subcutaneous injections of insulin during the last 4 weeks maintained the enzyme activity in the control range in both segments. There was a positive correlation between sucrase activity and blood glucose level in the pancreatectomized rats. Hyperglycemia in normal rats induced by intravenous infusion of 30% glucose solution over 48 hours enhanced the sucrase activity in the jejunum. Furthermore, insulin administration with a glucose solution inhibited the enhancement of enzyme activity. These findings suggest that hyperglycemia itself might play an important role in the diabetic increment of sucrase activity.     

Induction of intestinal differentiation by systemic and not by luminal corticosterone in adrenalectomized rat pups

Potential effects of corticosterone (cort) from maternal milk on intestinal differentiation were studied using adrenalectomized (adx) rat pups fed a formula containing differing amounts of cort. Formula cort concentrations in the range found in milk (0.1-0.5 micrograms/ml) increased the survival of adx rats, but did not induce intestinal differentiation. Formulae containing 1.0-50.0 micrograms/ml cort caused a dose-dependent elevation of serum cort concentrations and jejunal maltase activity and precocious jejunal sucrase induction. Adx rats receiving the formula containing 10 micrograms/ml cort showed serum cort concentrations similar to those in day 15 control rats and jejunal sucrase and maltase activities equivalent to those in day 18-20 control rats, suggesting that the rise in serum cort that occurs during postnatal development suffices to modulate intestinal differentiation. To distinguish between direct local and systemic effects of luminal cort on intestinal differentiation, expression of sucrase was determined in jejunal isografts and in host jejunum from adx rats fed luminal cort. Jejunal isografts and host jejunum expressed similar sucrase activities and showed similar immunofluorescent staining. Moreover, administration of cort by continual ip infusion was more effective than continual intragastric infusion in inducing intestinal sucrase and maltase activities. These data imply that luminal cort is absorbed and transported into the systemic circulation before inducing intestinal epithelial cell differentiation through the systemic route.     

Evolutionary matches of enzyme and transporter capacities to dietary substrate loads in the intestinal brush border

Safety factors of enzymes and transporters are defined as the ratio of V_max (maximal reaction rates at high substrate concentrations) to the reaction rate under actual physiological conditions. Although corresponding safety factors have been measured for macroscopic biological structures and for human-engineered structures, safety factors have been little studied at the molecular level. Some evolutionary considerations suggest that safety factors should be modestly in excess of 1.0 (“enough but not too much”) and should tend to be similar for the various steps of a pathway consisting of two or more elements arranged in series. Hence we used a preparation of intact mouse small intestine to measure V_max values (capacities) of brush-border sucrase (yielding glucose plus fructose) and of the brush-border glucose transporter, for comparison with each other and with dietary sucrose loads. Load was manipulated by varying dietary sucrose level or by studying lactating mice with increased energy requirements. Capacities both of sucrase and the glucose transporter increased with sucrose load (i.e., both proteins are inducible) and remained approximately matched to each other except on a carbohydrate-free diet. Their safety factors decreased from ca. 2.7 at low load to 1.0 at high load. Thus, neither sucrase nor the glucose transporter is the rate-limiting step for sucrose digestion; both steps are equally limiting. The modest safety factors and matched capacities must be genetically programmed through natural selection, with benefits of excess capacities being balanced against costs of biosynthetic energy and limited membrane space.     

Proximal small intestinal mucosal injury

The effect of chronic intragastric infusion of hypertonic mannitol on small intestinal mucosal structure and function was studied in adult rats. Animals were gavagefed 20% mannitol (1300 mosm) at a dose of 5 ml/100 g body weight daily for seven days. Control animals were gavagefed tap water on the same schedule. On day 8, the animals were anesthetized, the duodenum cannulated, and a test sugar (glucose, glucose polymer, lactose, sucrose, or maltose) was infused at a dose of 0.5 g/kg body weight in 2.5 ml distilled water over less than 1 min. Portal vein glucose was measured at 30-min intervals from 0 to 120 min. Mannitol treatment resulted in histologic and biochemical alterations (reduced lactase, sucrase, maltase) limited to the proximal small intestine compared to the control group. The absorption of glucose and glucose polymers was similar in mannitoltreated and control animals. In contrast, digestion and absorption of lactose, sucrose, and maltose was significantly diminished in mannitol-treated animals when compared to controls. No changes in permeability to polyethylene glycol 4000 or Na⁺-coupled glucose transport were observed in mannitol-treated animals compared to controls. These data suggest that when the intestinal mucosa is exposed to hyperosmolar loads that the digestive capacity for disaccharides is suppressed more than its glucose absorptive capacities. Furthermore, glucose oligomers may be more readily digested and absorbed than disaccharides, in this setting, due, in part, to the proximal injury and less pronounced proximal-distal gradient for glucoamylase than other brushborder carbohydrases.This study was funded in part by the Ralph Hochstetter Medical Research Fund in honor of Dr. Henry C. and Bertha H. Bus well, and by a grant-in-aid from USAID CDPE-5940-A-00-4019-00).     

桑叶总黄酮对糖尿病大鼠小肠双糖酶的抑制作用

目的 观察桑叶总黄酮对糖尿病大鼠的降糖作用及其对大鼠双糖酶活性的影响。方法 糖尿病大鼠灌胃给桑叶总黄酮，观察给药前后血糖变化；剥离小肠刷状缘膜，匀浆后加桑叶总黄酮测定对双糖酶活性的抑制率；大鼠小肠注入麦芽糖，30、60、120分钟后取门静脉、外周静脉血，测门－外周静脉血糖差。结果 桑叶总黄酮使糖尿病大鼠血糖降低；对蔗糖酶、麦芽糖酶、乳糖酶活性抑制率依次达68.0%、47．1％、27．8％；使注入麦芽糖后门－外周静脉血糖浓度差降低。结论 桑叶总黄酮通过抑制大鼠小肠双糖酶活性有显著的降血糖作用。     

Dietary fat-induced increase in blood pressure and insulin resistance in rats

OBJECTIVES: To determine whether the dietary-fat-induced increase in blood pressure is caused by excess energy intake or the fat composition of the diet, what type of fat increases the blood pressure, and whether insulin resistance is involved in the dietary-fat-induced increase in blood pressure. METHODS: In a series of experiments, rats received: chow alone or chow supplemented with lard or sucrose to provide 33% of a total energy content increased by 50%; chow alone or chow in which 50% of the energy content was from substituted lard, safflower oil or medium-chain triglyceride oil; or chow alone or chow in which 50% of the energy content was from substituted lard, with or without troglitazone. Systolic blood pressure (SBP) was measured every week during each 8-week feeding period. A steady-state serum glucose method was used to determine the insulin sensitivity after the lard substitution with or without troglitazone. RESULTS: Both the lard and sucrose enrichment increased SBP and body weight compared with controls. Lard substitution significantly increased SBP and immunoreactive insulin, although body weight did not differ from control. Neither a diet substituted with safflower oil nor one substituted with medium-chain triglyceride oil influenced SBP. Troglitazone completely inhibited the increase in SBP and immunoreactive insulin induced by the lard. The steady-state serum glucose concentration was significantly greater after the lard substitution than after isoenergetic chow; this effect also was reversed by troglitazone. CONCLUSION: Chronic feeding with lard increased SBP in rats, independently of excess energy intake. Of the fats tested, lard exerted an intrinsic pressor effect. Troglitazone reversed the lard-induced increase in SBP.     

Effect of copper on insulin release by the intact rat pancreas and the perfused rat pancreas

In previous studies, we have shown that rats fed a copper-poor diet have an impaired glucose tolerance and insulin response to an oral glucose load. Furthermore, CuCl2 X 2H2O added to the incubation medium stimulated glucose incorporation into the diaphragm glycogen and epididimal fat of rats. The purpose of the present study was to examine the effect of copper on insulin release in vivo and in the perfused pancreas. Copper chloride stimulated the insulin release by the perfused pancreas of rats fed laboratory chow (copper content, 6.7 ppm). Stimulation with 0.5 mg/dl CuCl2 X 2H2O for 20 min resulted in release of 14.7 +/- 3.1 compared with 18.9 +/- 4.3 mu insulin following stimulation with 16.7 mM glucose. The CuCl2 X 2H2O effect depended on the presence of calcium in the medium--as with other insulinotropic agents--but not on the presence of magnesium. Animals fed a copper-poor (1.2 ppm) sucrose diet have a selective impairment to i.v. glucose-induced insulin stimulation, but not to i.v. arginine or aminophylline stimulation when compared with controls fed a sucrose copper-supplemented diet or a laboratory chow diet. This selective beta cell defect is not necessarily genetically inherited and may be acquired. The role of copper on insulin release is discussed.     

Long-term therapeutic effects of voglibose,a potent intestinal alpha-glucosidase inhibitor,in spontaneous diabetic GK rats

The effect of long-term (6 months) administration of voglibose in a dietary mixture (10 ppm) on intestinal disaccharidase activity was examined in non obese type 2 diabetes model Goto-Kakizaki (GK) rats. The postprandial blood glucose level in voglibose-treated GK rats was significantly lower than in untreated GK rats (190+/-19 vs. 250+/-25 mg/dl, P<0.01; 1 h, 212+/-23 vs. 256+/-20, P<0.05; 2 h), and the activities of maltase, sucrase, and isomaltase remained significantly lower throughout the 6 months of voglibose treatment. The expressions of protein and mRNA of sucrase-isomaltase (SI) complex were significantly higher in voglibose-treated GK rats. Voglibose administration then was stopped after 6 months of treatment. The mRNA level and protein level of the SI complex became normalized during the interruption of drug administration, and disaccharidase activities increased almost to the level of the untreated group 1 month after treatment was stopped. After 1 day of re-administration of the drug, however, disaccharidase activities again became significantly inhibited. These results indicate that voglibose may improve glucose tolerance since it inhibits activities of disaccharidases in spite of increasing the expression of them on intestine, furthermore voglibose may be reversible and reproducible through interruption and re-administration.     

Effect of high sucrose diet on insulin secretion and insulin action. A study in rats with non-insulin-dependent diabetes induced by streptozotocin

Summary The effects of chronic high sucrose feeding for 1 month on in vivo and in vitro insulin secretion and on in vivo insulin action were studied in rats with non-insulin-dependent diabetes. As compared to the standard diet, the high sucrose diet induced an increase of the in vivo insulin response to an intravenous load and deteriorated the glucose tolerance as attested by significantly lower rates of glucose disppearance (K values, p<0.001). The increased insulin secretion in response to glucose in vivo seems to be related to a slight increase of the pancreatic B-cell reactivity to glucose, since it was still observed in vitro with the isolated perfused pancreas preparation. By contrast, B cells of sucrose-fed rats exhibited in vitro a significantly lowered (p<0.01) response to acetylcholine and arginine. The insulin action in the sucrose-fed diabetic rats was quantified in vivo with the insulin-glucose clamp technique. The effects of different concentrations of insulin on glucose production and glucose utilisation were studied in anaesthetized rats while in the postabsorptive state. The basal glucose utilisation was found significantly higher (p<0.001) in sucrose-fed rats. During the clamp studies the glucose utilisation induced by submaximal (450 mU/l) insulin level was significantly less important (p<0.01) in the sucrose-fed rats than in the chow-fed rats. Following a maximal hyperinsulinaemia (5000 mU/l) the glucose utilisation was similar in both groups. This suggests that insulin-mediated glucose uptake is decreased over the range of submaximal plasma insulin levels in the sucrose-fed diabetic rats. In the basal state hepatic glucose production was significantly higher (p<0.001) in sucrose-fed rats. During the clamp studies, the suppression of glucose production induced by submaximal or maximal insulin levels was significantly less effective (p<0.01) in the sucrose-fed rats as compared to chow-fed rats, thus suggesting that the liver becomes resistant to insulin action after sucrose feeding. Finally, these results suggest that restriction of complex carbohydrates in favor of sucrose in insulin-deficient rats leads to metabolic events likely to develop insulin resistance in target tissues.     

Effect of acarbose on glucose and insulin response to sucrose load in reactive hypoglycemia

The aim of the present study was to evaluate the acute effect of acarbose, an alpha-glycosidase inhibitor, on glycemic and insulin response to an oral sucrose load in sixteen patients suffering from idiopathic reactive hypoglycemia. In each subject, two oral sucrose tolerance tests (45 g/m2 body surface) were performed with either placebo or acarbose in a double-blind random order. Compared with placebo, acarbose dramatically flattened the blood glucose curve with values significantly lower from 30 to 90 min and higher from 150 to 240 min. Moreover the magnitude of both glucose peak and nadir, and rate of blood glucose rise and fall were significantly reduced by acarbose as was the hypoglycemic index. Plasma insulin levels from 30 to 120 min, insulin peak and area under the insulin curve were significantly lower after ingestion of acarbose. Thus, in reducing the early rise in blood glucose and insulin after sucrose ingestion, acarbose prevents the occurrence of reactive hypoglycemia; the present study confirms that this drug may be of value in the treatment of reactive hypoglycemia.     

Effect ofStrongyloides ratti on small bowel function in normal and immunosuppressed host rats

Although Strongyloides stercoralis is a common parasite, little is known about its effect on intestinal function. Published clinical studies are difficult to evaluate and compare because of the inability to differentiate the effects of the parasite load from that of various other coexisting features such as bacterial overgrowth, multiparasitism, malnutrition, or tropical sprue. Using a rat model where these problems do not occur, we found that Strongyloides ratti did not inhibit intestinal function in the healthy rat. In fact, in normal rats S. ratti appeared to increase ileal sucrase activity. In contrast, in the methylprednisolone-treated rat, S. ratti produced a decrease in lactase and sucrase activity and an increase in alkaline phosphatase activity. S. ratti had no effect on 3-O-methylglucose uptake or D-xylose absorption in either group. These results suggest that S. ratti has little effect on small bowel function in a healthy rat but can cause minor alterations in intestinal function in an immunosuppressed, methylprednisolone-treated, malnourished host. These results are also consistent with clinical observations seen with S. stercoralis in humans and with another nematode, Ascaris suus, in the pig model.     

The effect of alpha-glucosidase inhibition on intestinal disaccharidase activity in normal and diabetic mice

Acarbose is a potent alpha-glycosidase inhibitor which decreases postprandial hyperglycemia when administered with a carbohydrate-containing meal. The genetically diabetic mouse C57 BLKsJ db/db represents a model of type II, noninsulin dependent diabetes mellitus. Characteristic features of this animal include hyperglycemia, hyperinsulinemia, hyperphagia, and the development of obesity and widespread pathologic abnormalities. To evaluate the effects of Acarbose on intestinal disaccharidase activity, groups of normal and diabetic mice were given Acarbose as a drug-food mixture in doses of 20 (A-20) and $\text{40 (A-40) mg}\text{100 g}$ food. Sucrase activity was measured in intestinal homogenates and on the mucosal surface of proximal, middle, and distal segments of jejunoileum. In normal mice, sucrase activity was significantly increased in mid- and distal-intestinal segments following 2 wk of Acarbose in both A-20 and A-40 groups. No changes were noted following 5 and 10 days of drug treatment. Acarbose did not influence body weight, food:water intake or fasting blood glucose. When compared to normal mice, untreated diabetics had significantly more protein, DNA, and sucrase activity throughout the small intestine. Following 10 wk of Acarbose administration, both A-20 and A-40 groups showed increased sucrase activity in intestinal homogenates of distal segments. Surface mucosal sucrase activity however was slightly decreased in proximal intestinal segments as a result of drug therapy, with no changes in middle and distal segments. Acarbose did not influence body weight, food intake or fasting blood glucose, but water consumption and glucosuria were significantly decreased. Experimental diabetes mellitus is associated with significant alterations in enzyme activity and protein content of the brush border membrane of the small intestine. Acarbose administration influences both sucrase activity and distribution in normal and diabetic mice. The mechanisms responsible for these changes and their potential clinical importance remain to be determined.     

Effect of food intake on intestinal absorption and mucosal hydrolases in alloxan diabetic rats

The relation between food intake and enzyme activity of the small intestine and rate of intestinal absorption were studied in rats 15 days after induction of alloxan diabetes. Diabetic rats were given an ad lib. semisynthetic diet or a restricted diet on the basis of either daily intake or body weight. The rates of absorption of 5mM D-galactose and L-valine were determined in vitro by the everted sac method. The rates of absorption of the substances, expressed per unit weight or per length of intestine, were higher in diabetic rats than in controls, regardless of the amount of food consumed. Maltase and sucrase activities were significantly increased in diabetic rats, regardless of the amount of food consumed. The activity of intestinal alkaline phosphatase was increased in diabetic rats fed ad lib., but not in those on a restricted diet. These findings suggest that in alloxan diabetic rats the increased disaccharidase activity in the small intestine is due to insulin deficiency, and that the increased activity of alkaline phosphatase is only a secondary effect of insulin deficiency, caused by increased food intake resulting from insulin deficiency.     

Effects of diabetes and elevated glucose on nitrergic relaxations in the isolated duodenum of the rat

Nitrergic relaxations of the isolated duodenum, induced by streptozotocin, were investigated in the experimental 8-week diabetes rat model. The effects of elevated glucose were also examined in the incubated duodenal muscles (in Krebs-Henseleit solution containing 44 mM glucose for 6 h) taken from nondiabetic rats. The relaxations induced by electrical field stimulation (EFS) and nicotine were significantly reduced in diabetic rats compared with control rats. Incubating of duodenal tissues in medium containing elevated glucose revealed significantly impaired relaxations to EFS and nicotine compared to responses obtained after normal glucose incubation. However, the relaxant responses to sodium nitroprusside and papaverine were similar in all groups. Incubating in hyperosmolar solutions containing sucrose, the relaxant responses were not affected. In conclusion, impairment of NO-mediated relaxations in diabetes may be related to hyperglycemia. The alterations caused by elevated glucose are not due to a hyperosmotic effect because the same concentration of sucrose had no effect on the relaxations.     

Effects of substitution of glucose-oligosaccharides by sucrose in a defined formula diet on intestinal disaccharidases,hepatic lipogenic enzymes and carbohydrate metabolism in young rats

We have studied the effect of substitution of glucose-oligosaccharides by sucrose in a widely used high nitrogen defined formula diet, Vivonex-HN (Eaton Laboratories, Norwich, New York) on weanling rats for an experimental period of 5 wk; (1) The food consumption and growth rate in both G group (glucose-oligosaccha ride containing Vivonex-HN diet) and S group (sucrose substituted Vivonex-HN diet) were significantly lower than C group (laboratory chow fed control) (Student's p < 0.001), but there was no significant difference between G and S groups, (2) Food efficiencies were significantly higher in C group than in either G or S groups, (3) Not only sucrase but also maltase and trehalase were induced in the distal gut in S group, while in C group, maltase activity remained the same and sucrase activity decreased significantly, (4) The activities of hepatic lipogenic enzymes (glucose-6-phosphate dehydrogenase, malic enzyme, 6-phosphogluconate dehydrogenase) increased greatly in G group (Student's t, p < 0.001 between C and G) and even more so in S group (Wilcoxon's p < 0.002 between G and S) compared with C group, (5) Total lipid and cholesterol contents in the liver as well as in the plasma were higher in S group than in G group. The relative liver weights also were higher in S group than in G group. The weights of epididymal fat pad did not differ significantly among all three groups, and (6) The values of hematocrit, glucose and insulin did not differ significantly in the plasma of blood collected by cardiac puncture of all three groups. But, significantly lower levels of lactate were observed throughout the course of the experiment in the plasma of G and S groups compared with the C group. Also, the plasma protein of G and S groups were significantly lower than C group at weeks 2 and 4 (Student's t, p < 0.003). We postulate (1) that the structural genes for disaccharidases may be subject to a common genetic control which accepts several di- and oligosaccharides as inducers, and (2) that the induction of hepatic lipogenic enzymes may be mediated by lactate in the portal blood rather than by glucose or fructose. We also offer a caution for prolonged use of sucrose or fructose as the major source of carbohydrate until the potentially deleterious lipogenic effect of fructose is more critically evaluated.     

Anaesthesia and insulin secretion: The effects of diethyl ether,halothane, pentobarbitone sodium and ketamine hydrochloride on intravenous glucose tolerance and insulin secretion in the rat

Summary Fasting hyperglycaemia occurred in 48 h starved rats after 30 min of anaesthesia with ether or halothane. Plasma insulin increased only with ether. Halothane caused basal hyperglycaemia in fed rats, but decreased plasma insulin by 50%. Intravenous pentobarbitone (30 mg/kg) did not affect blood glucose in starved rats, but decreased plasma insulin with a small rise in blood glucose in fed rats. Following intravenous glucose (0.5 g/kg), hyperglycaemia and impaired glucose tolerance with normal insulin/glucose ratios occurred in starved animals anaesthetised with ether and pentobarbitone. The latter had no effect on glucose tolerance in fed rats. In contrast, halothane caused hyperglycaemia without glucose intolerance in starved animals, but decreased the insulin response by 40% in fed animals. Ketamine (30 mg/ kg) caused only a 15% increase in glucose area in starved rats and was otherwise without effect. Halothane had no significant effect on glucose stimulated insulin secretion in the isolated perfused rat pancreas. — Possible mechanisms for these effects are discussed.Presented in part at the Meeting of the Medical and Scientific Section of the British Diabetic Association, York, England 14–15 April, 1972.     

Evaluation of differential disaccharide excretion in urine for non-invasive investigation of altered intestinal disaccharidase activity caused by alpha-glucosidase inhibition, primary hypolactasia, and coeliac disease.

BACKGROUND/AIM: The reliability of a quantitative method for the non-invasive assessment of intestinal disaccharide hydrolysis was assessed. METHODS: Differential excretion of intact disaccharide, expressed as ratios of lactulose to appropriate hydrolysable disaccharides in urine collected following combined ingestion, has been investigated in healthy volunteers with drug induced alpha-glucosidase inhibition, in subjects with primary hypolactasia, and patients with coeliac disease. RESULTS: Oral administration of the alpha-glucosidase inhibitor 'Acarbose' (BAY g 5421, 200 mg) together with sucrose and lactulose increased the urinary sucrose/lactulose excretion ratios (% dose/10 h) fivefold. The effect was quantitatively reproducible, a higher dose of 'Acarbose' (500 mg) increasing the excretion ratio to about 1.0 indicating complete inhibition of intestinal sucrase activity. The suitability of the method for measuring differences in dose/response and duration of action was assessed by comparing three different alpha-glucosidase inhibitors (BAY g 5421, BAY m 1099, and BAY o 1248) and found to be satisfactory. Subjects with primary adult hypolactasia had urine lactose/lactulose excretion ratios raised to values indicating reduced rather than complete absence of lactase activity whereas sucrose/lactulose ratios were not significantly affected. 'Whole' intestinal disaccharidase activity assessed by this method demonstrated impairment of lactase, sucrase, and isomaltase in eight, one, and seven, respectively, of 20 patients with coeliac disease. By contrast in vitro assay of jejunal biopsy tissue indicated pan-disaccharidase deficiency in all but five of these patients. This shows the importance of distinguishing between 'local' and 'whole' intestinal performance. CONCLUSIONS: Differential urinary excretion of ingested disaccharides provides a reliable, quantitative, and non-invasive technique for assessing profiles of intestinal disaccharidase activity.     

The effects of sucrose meal on insulin requirement in IDDM and its modulation by acarbose

The purpose of the present study was to evaluate the insulin requirement in response to sucrose meal in IDDM and its modulation by a disaccharidase inhibitor, Acarbose. After an overnight fast, the subjects (n = 9) were "hooked" to the artificial pancreas (Biostator) to maintain normoglycemia. Blood glucose and insulin requirement were recorded by the Biostator throughout the experiment. The patients were divided into two groups. In group I, five patients received increasing sucrose load (50, 75 and 100 g) with and without Acarbose 100 mg. After a 50 g sucrose meal with and without Acarbose, the peak postprandial (PP) blood glucose was 118 and 157 mg/dl and the insulin requirement was 3.9 and 7.8 units resulting in free plasma insulin peak of 34 and 59 microU/ml respectively. After a 75 g sucrose meal with and without Acarbose, the peak PC blood glucose was 134 and 166 mg/dl and the insulin requirement was 5.7 and 9.9 units resulting in free plasma insulin peak of 75 and 87 microU/ml. After a 100 g sucrose meal with and without Acarbose the peak PP blood glucose was 131 and 175 mg/dl and the insulin requirement was 6 and 12.8 units resulting in free plasma insulin peak of 50 and 69 microU/ml. In group II, four patients received increasing Acarbose dose with a fixed sucrose load (75 g). The PP blood glucose peaked at 161, 145, 120 and 102 mg/dl after 0, 50, 100, 200 mg of Acarbose respectively. The total insulin requirements were 12.9, 9.6, 4.3 and 3.1 units. The free plasma insulin was decreased by Acarbose treatment while plasma glucagon remained unaffected.(ABSTRACT TRUNCATED AT 250 WORDS)