Short-term and long-term effects of guar on postprandial plasma glucose, insulin and glucagon-like peptide 1 concentration in healthy rats.

Ingestion of guar gum decreases postprandial glycemia and insulinemia and improves sensitivity to insulin in diabetic patients and several animal models of diabetes. The aim of the present study was to compare the short-term and long-term effects of guar on plasma insulin and glucagon-like peptide 1 concentration in healthy rats. In the short-term experiments, the concomitant intragastric administration of glucose and guar reduced the early increment in plasma glucose, insulin and glucagon-like peptide 1 concentration otherwise induced by glucose alone. Comparable findings were made after twelve days of meal training exposing the rats to either a control or guar-enriched diet for fifteen minutes. Mean plasma glucose concentrations were lower while mean insulin concentrations were higher in the guar group than in the controls according to intragastric glucose tolerance tests conducted in overnight fasted rats maintained for 19 to 36 days on either the control or guar-enriched diet. The intestinal content of glucagon-like peptide 1 at the end of the experiments was also lower in the guar group. Changes in body weight over 62 days of observation were comparable in the control and guar rats. Thus, long-term intake of guar improves glucose tolerance and insulin response to glucose absorption, without improving insulin sensitivity, in healthy rats.     

Glucagon-like peptide 1 improved glycemic control in type 1 diabetes

BACKGROUND: Glucagon-like peptide-1 (GLP-1) and its agonists are under assessment in treatment of type 2 diabetes, by virtue of their antidiabetic actions, which include stimulation of insulin secretion, inhibition of glucagon release, and delay of gastric emptying. We examined the potential of GLP-1 to improve glycemic control in type 1 diabetes with no endogenous insulin secretion. METHODS: Dose-finding studies were carried out to establish mid range doses for delay of gastric emptying indicated by postponement of pancreatic polypeptide responses after meals. The selected dose of 0.63 micrograms/kg GLP-1 was administered before breakfast and lunch in 8-hour studies in hospital to establish the efficacy and safety of GLP-1. In outside-hospital studies, GLP-1 or vehicle was self-administered double-blind before meals with usual insulin for five consecutive days by five males and three females with well-controlled C-peptide-negative type 1 diabetes. Capillary blood glucose values were self-monitored before meals, at 30 and 60 min after breakfast and supper, and at bedtime. Breakfast tests with GLP-1 were conducted on the day before and on the day after 5-day studies. Paired t-tests and ANOVA were used for statistical analysis. RESULTS: In 8-hour studies time-averaged incremental (delta) areas under the curves(AUC) for plasma glucose through 8 hours were decreased by GLP-1 compared to vehicle (3.2 PlusMinus; 0.9, mean PlusMinus; se, vs 5.4 PlusMinus; 0.8 mmol/l, p <.05), and for pancreatic polypeptide, an indicator of gastric emptying, through 30 min after meals (4.0 PlusMinus; 3.1 vs 37 PlusMinus; 9.6 pmol/l, p <.05) with no adverse effects. Incremental glucagon levels through 60 min after meals were depressed by GLP-1 compared to vehicle (-3.7 PlusMinus; 2.5 vs 3.1 PlusMinus; 1.9 ng/l, p <.04). In 5-day studies, AUC for capillary blood glucose levels were lower with GLP-1 than with vehicle (-0.64 PlusMinus; 0.33 vs 0.34 PlusMinus; 0.26 mmol/l, p <.05). No assisted episode of hypoglycaemia or change in insulin dosage occurred. Breakfast tests on the days immediately before and after 5-day trials showed no change in the effects of GLP-1. CONCLUSION: We have demonstrated that subcutaneous GLP-1 can improve glucose control in type 1 diabetes without adverse effects when self-administered before meals with usual insulin during established intensive insulin treatment programs.     

Suppression of glucose production by GLP-1 independent of islet hormones: a novel extrapancreatic effect

Glucagon-like peptide-1 (GLP-1) is an intestinal hormone that stimulates insulin secretion and decreases glucagon release. It has been hypothesized that GLP-1 also reduces glycemia independent of its effect on islet hormones. Based on preliminary evidence that GLP-1 has independent actions on endogenous glucose production, we undertook a series of experiments that were optimized to address this question. The effect of GLP-1 on glucose appearance (Ra) and glucose disposal (Rd) was measured in eight men during a pancreatic clamp that was performed by infusing octreotide to suppress secretion of islet hormones, while insulin and glucagon were infused at rates adjusted to maintain blood glucose near fasting levels. After stabilization of plasma glucose and equilibration of [3H]glucose tracer, GLP-1 was given intravenously for 60 min. Concentrations of insulin, C-peptide, and glucagon were similar before and during the GLP-1 infusion (115 +/- 14 vs. 113 +/- 11 pM; 0.153 +/- 0.029 vs. 0.156 +/- 0.026 nM; and 64.7 +/- 11.5 vs. 65.8 +/- 13.8 ng/l, respectively). With the initiation of GLP-1, plasma glucose decreased in all eight subjects from steady-state levels of 4.8 +/- 0.2 to a nadir of 4.1 +/- 0.2 mM. This decrease in plasma glucose was accounted for by a significant 17% decrease in Ra, from 22.6 +/- 2.8 to 19.1 +/- 2.8 micromol. kg-1. min-1 (P < 0.04), with no significant change in Rd. These findings indicate that, under fasting conditions, GLP-1 decreases endogenous glucose production independent of its actions on islet hormone secretion.     

Controlled release of tamoxifen citrate encapsulated in cross-linked guar gum nanoparticles

Natural polysaccharides, due to their outstanding merits, have received more and more attention in the field of drug delivery. In the present study tamoxifen citrate, TMX (a non-steroidal antiestrogenic drug) loaded guar gum nanoparticles, GG NPs, crosslinked with glutaraldehyde were prepared for treatment of breast cancer. An oil in water (o/w) emulsion polymer cross-linking method was employed for preparation of blank and drug loaded sustained release nature biodegradable nanoparticles. Prepared nanoparticles were characterized by morphology in scanning electron microscope (SEM), size distribution in transmission electron microscope (TEM), TMX loading by high performance liquid chromatography (HPLC) and in vitro drug release characteristics. An overall sustained release of the drug from the biodegradable nanoparticles was observed in in vitro release studies. The release of TMX from GG NPs was found to be effected by guar gum and glutaraldehyde concentration. Regression coefficient (R²) analysis suggested that the predominant mechanism behind the drug release from the nanoparticles was time dependent release and diffusion. In vivo studies on female albino mice demonstrated maximum uptake of the drug by mammary tissue after 24 h of administration with drug loaded guar gum nanoparticles in comparison with that with the tablet form of the drug. These findings demonstrate that controlled release of TMX from GG NPs could be a potential alternative pharmaceutical formulation in passive targeting of TMX in breast cancer treatments.     

Endomucin is expressed in embryonic dorsal aorta and is able to inhibit cell adhesion

Glucagon-like peptide-1 (GLP-1) is an incretin, which induces glucose-dependent insulin secretion. GLP-1 is rapidly degraded by dipeptidyl peptidase IV (DPPIV) after its release. We investigated whether DPPIV-deficient F344/DuCrj rats show improved glucose tolerance when compared with DPPIV-positive F344/Jcl rats. Oral glucose tolerance test indicated improved glucose tolerance in F344/DuCrj rats, but blood glucose levels of the two strains were almost the same 120 min after the glucose bolus. Valine-pyrrolidide, a DPPIV inhibitor, had no effect on the glucose tolerance of F344/DuCrj rats, but improved that of F344/Jcl rats. Enhanced insulin secretion and high plasma active GLP-1 levels were detected in an intraduodenal glucose tolerance test. Glucose tolerance is improved in DPPIV-deficient F344/DuCrj rats via enhanced insulin release mediated by high active GLP-1 levels. Our results suggest that DPPIV inhibition is a rational strategy to treat diabetic patients by improving glucose tolerance with low risk of hypoglycemia.     

Incretin and islet hormonal responses to fat and protein ingestion in healthy men

Glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) regulate islet function after carbohydrate ingestion. Whether incretin hormones are of importance for islet function after ingestion of noncarbohydrate macronutrients is not known. This study therefore examined integrated incretin and islet hormone responses to ingestion of pure fat (oleic acid; 0.88 g/kg) or protein (milk and egg protein; 2 g/kg) over 5 h in healthy men, aged 20-25 yr (n=12); plain water ingestion served as control. Both intact (active) and total GLP-1 and GIP levels were determined as was plasma activity of dipeptidyl peptidase-4 (DPP-4). Following water ingestion, glucose, insulin, glucagon, GLP-1, and GIP levels and DPP-4 activity were stable during the 5-h study period. Both fat and protein ingestion increased insulin, glucagon, GIP, and GLP-1 levels without affecting glucose levels or DPP-4 activity. The GLP-1 responses were similar after protein and fat, whereas the early (30 min) GIP response was higher after protein than after fat ingestion (P<0.001). This was associated with sevenfold higher insulin and glucagon responses compared with fat ingestion (both P<0.001). After protein, the early GIP, but not GLP-1, responses correlated to insulin (r(2)=0.86; P=0.0001) but not glucagon responses. In contrast, after fat ingestion, GLP-1 and GIP did not correlate to islet hormones. We conclude that, whereas protein and fat release both incretin and islet hormones, the early GIP secretion after protein ingestion may be of primary importance to islet hormone secretion.     

Interrelation between glucose, insulin, C-peptide and 3-hydroxybutyrate in plasma and amniotic fluid in last trimester diabetic women without residual betacell function

The relationship between maternal plasma and amniotic fluid (AF) concentrations of glucose, insulin, C-peptide and 3-hydroxybutyrate (3-HB) was analysed between 45 to 140 minutes after a standardized breakfast in 8 type I diabetic women without residual betacell function and in 13 nondiabetic control women during the last trimester of gestation. AF levels of both glucose and C-peptide were slightly and AF insulin levels significantly (P less than 0.05) elevated above normal in the diabetic women. 3-HB levels in plasma and in AF were significantly (P less than 0.05) elevated in the diabetic group between 45 to 65 minutes after breakfast. AF insulin and glucose was significantly correlated in the diabetic group (r = 0.96, P less than 0.05). During the 2 hour study period AF levels of glucose, insulin and C-peptide remained essentially unchanged in both groups of women. Changes in maternal plasma 3-HB concentrations seemed to be more rapidly reflected in AF.     

Reduced GLP-1 and insulin responses and glucose intolerance after gastric glucose in GRP receptor-deleted mice

By applying a newly developed ELISA technique for determining biologically active intact glucagon-like peptide [GLP-1, GLP-1-(7-36)amide] in mouse, plasma baseline GLP-1 in normal NMRI mice was found to be normally distributed (4.5 +/- 0.3 pmol/l; n = 72). In anesthetized mice, gastric glucose (50 or 150 mg) increased plasma GLP-1 levels two- to threefold (P < 0.01). The simultaneous increase in plasma insulin correlated to the 10-min GLP-1 levels (r = 0.36, P < 0.001; n = 12). C57BL/6J mice deleted of the gastrin-releasing peptide (GRP) receptor by genetic targeting had impaired glucose tolerance (P = 0.030) and reduced early (10 min) insulin response (P = 0.044) to gastric glucose compared with wild-type controls. Also, the GLP-1 response to gastric glucose was significantly lower in the GRP receptor-deleted mice than in the controls (P = 0.045). In conclusion, this study has shown that 1) plasma levels of intact GLP-1 increase dose dependently on gastric glucose challenge in correlation with increased insulin levels in mice, and 2) intact GRP receptors are required for normal GLP-1 and insulin responses and glucose tolerance after gastric glucose in mice.     

Effects of oral fructose and glucose on plasma GLP-1 and appetite in normal subjects.

Oral glucose is a potent stimulant of glucagon-like peptide-1 (GLP-1) secretion. The effect of oral fructose on GLP-1 secretion in humans is unknown. The aims of this study were to determine (i) whether oral fructose stimulates GLP-1 secretion and (ii) the comparative effects of oral glucose and fructose on appetite. On 3 separate days, 8 fasting healthy males received, in single-blind randomized order (i) 75 g glucose, (ii) 75 fructose, or (iii) 75 g glucose followed by 75 g fructose I h later. Venous glucose, insulin and GLP-1 were measured. Appetite was assessed by visual analog questionnaires and intake of a buffet meal. Whereas glucose and fructose both increased plasma glucose, insulin and GLP-1 (P < 0.000)] for all), the response to glucose was much greater (P < 0.005 for all). There was no increase in plasma GLP-1 when fructose was given after glucose. There was no difference in food intake after oral glucose or fructose. We conclude that oral fructose (75 g) stimulates GLP-1 (and insulin) secretion, but the response is less than that to 75 g glucose. These observations suggest that neither GLP-1 nor insulin play a major role in the regulation of satiation.     

Total parenteral nutrition-stimulated activity of inducible nitric oxide synthase in rat pancreatic islets is suppressed by glucagon-like peptide-1.

Long-term total parenteral nutrition (TPN) is associated with elevated plasma lipids and a marked decrease of glucose-stimulated insulin release. Since nitric oxide (NO) has been shown to modulate negatively the insulin response to glucose, we investigated the influence of TPN-treatment on isoforms of islet NO-synthase (NOS) activities in relation to the effect of glucagon-like peptide-1 (GLP-1), a known activator of glucose-stimulated insulin release. Isolated islets from TPN rats incubated at basal glucose (1 mmol/l) showed a modestly increased insulin secretion accompanied by an enhanced accumulation of islet cAMP and cGMP. In contrast, TPN islets incubated at high glucose (16.7 mmol/l) displayed an impaired insulin secretion and a strong suppression of islet cAMP content. Moreover, islet inducible NOS (iNOS) as well as islet cGMP content were greatly increased in these TPN islets. A dose-response study of GLP-1 with glucose-stimulated islets showed that GLP-1 could overcome and completely restore the impaired insulin release in TPN islets, bringing about a marked increase in islet cAMP accumulation concomitant with heavy suppression of both glucose-stimulated increase in islet cGMP content and the activities of constitutive NOS (cNOS) and iNOS. These effects of GLP-1 were mimicked by dibutyryl-cAMP. The present results show that the impaired insulin response of glucose-stimulated insulin release seen after TPN treatment is normalized by GLP-1. This beneficial effect of GLP-1 is most probably exerted by a cAMP-induced suppression of both iNOS and cNOS activities in these TPN islets.     

Improved Hypolipidemic Effects of Xanthan Gum-Galactomannan Mixtures in Rats

This study describes the effects of mixtures of xanthan gum and galactomannan, guar gum, or locust bean gum, on the lipids in plasma and liver in non-diabetic and diabetic rats. Non-diabetic rats were fed cholesterol-free diets with 3% guar gum, locust bean gum, or xanthan gum (3G, 3L, and 3X), or a mixture of xanthan gum and guar gum or locust bean gum (1:2, w/w) (2G1X, 2L1X) for 2 weeks. Rats fed diets not containing these polysaccharides were used as controls. The total cholesterol in plasma and the triacylglycerol in liver were significantly lowered in rats fed the 2G1X diet. The 3G, 3X, 3L, and 2L1X diets showed no significant effect on the total cholesterol and triacylglycerol in plasma and liver. In the streptozotocin-induced (STZ) diabetic rats, the total cholesterol in plasma was lowered in rats fed the 3G, 3X or 2G1X diet for 4 weeks, and the 2G1X diet was more effective than the 3G and 3X diets. The triacylglycerol in plasma in STZ diabetic rats was also significantly lowered by the 2G1X diet. These results showed that a mixture of xanthan gum and guar gum has an improved hypolipidemic effect on non-diabetic and STZ diabetic rats. The effects of the 2G1X diet on the diabetic symptoms in STZ diabetic rats, suppression of food and water intakes, decrease in glucose in urine, and lowering of plasma glucose, were also observed.     

Guar gum consumption in adolescent and adult rats: short- and long-term metabolic effects

Metabolic responses to short- and long-term guar gum consumption were studied in adolescent and adult rats. For the long-term study, male adolescent rats were divided into four groups (n = 60/group) and fed guar gum, cellulose, or bran diet for 67 weeks. Metabolic studies (food--water intake, feces--urine output, body weight, carbohydrate tolerance) were performed eight times during the 67 weeks. The guar gum group consumed less diet throughout the entire study and gained less weight over the first 20 weeks compared with the cellulose and bran groups. A second bran-fed group was food restricted over the first 20 weeks to match the reduced weight gain of the guar gum group and then fed ad libitum. Reduced plasma glucose excursions were measured for only the guar gum group after both fibre-free glucose and sucrose challenges at weeks 6, 12, and 18; from 24 to 64 weeks all four groups had similar glucose tolerance responses. Twenty-four hour urinary glucose excretion was similar during all eight metabolic studies up to 64 weeks for guar gum and cellulose groups. In the short-term study, male adolescent (200 g; n = 10/group) and adult (630 g; n = 15/group) rats were divided into five and four groups, respectively, and fed guar gum, guar by-product (GBP), cellulose, or bran diet for 6 weeks. A metabolic study was performed during the 6th week. Adolescent rats fed guar gum or GBP diets gained less weight than the cellulose group; only the guar gum group displayed improved carbohydrate tolerance.(ABSTRACT TRUNCATED AT 250 WORDS)     

Improved hypolipidemic effects of xanthan gum-galactomannan mixtures in rats

This study describes the effects of mixtures of xanthan gum and galactomannan, guar gum, or locust bean gum, on the lipids in plasma and liver in non-diabetic and diabetic rats. Non-diabetic rats were fed cholesterol-free diets with 3% guar gum, locust bean gum, or xanthan gum (3G, 3L, and 3X), or a mixture of xanthan gum and guar gum or locust bean gum (1:2, w/w) (2G1X, 2L1X) for 2 weeks. Rats fed diets not containing these polysaccharides were used as controls. The total cholesterol in plasma and the triacylglycerol in liver were significantly lowered in rats fed the 2G1X diet. The 3G, 3X, 3L, and 2L1X diets showed no significant effect on the total cholesterol and triacylglycerol in plasma and liver. In the streptozotocin-induced (STZ) diabetic rats, the total cholesterol in plasma was lowered in rats fed the 3G, 3X or 2G1X diet for 4 weeks, and the 2G1X diet was more effective than the 3G and 3X diets. The triacylglycerol in plasma in STZ diabetic rats was also significantly lowered by the 2G1X diet. These results showed that a mixture of xanthan gum and guar gum has an improved hypolipidemic effect on non-diabetic and STZ diabetic rats. The effects of the 2G1X diet on the diabetic symptoms in STZ diabetic rats, suppression of food and water intakes, decrease in glucose in urine, and lowering of plasma glucose, were also observed.     

Effects of increasing doses of glucagon-like peptide-1 on insulin-releasing phases during intravenous glucose administration in mice

The increase in insulin secretion caused by glucagon-like peptide-1 (GLP-1) and GLP-1 mimetics observed during an intravenous glucose test (IVGTT) has been reported in both normal and disease animal models, as well as in humans. In this study, a hierarchical population modeling approach is used, together with a previously reported model relating glucose to insulin appearance, to determine quantitative in vivo dose-response relationships between GLP-1 dose level and both first- and second-phase insulin release. Parameters of the insulin kinetic model were estimated from the complete set of glucose and insulin data collected in 219 anesthetized nonfasted NMR-imaged mice after intravenous injection of glucose (1 g/kg) alone or with GLP-1 (0.03-100 nmol/kg). The resulting dose-response curves indicate a difference in GLP-1 effect on the two release phases, as is also evident from the different ED(50) parameter values (0.107 vs. 6.65 nmol/kg for phase 1 vs. phase 2 insulin release parameters). The first phase of insulin release is gradually augmented with increasing GLP-1 dose, reaching saturation at a dose of ~1 nmol/kg, while the second-phase release changes more abruptly at GLP-1 doses between 3 and 10 nmol/kg and shows a more pronounced 100-fold increase between control and the high GLP-1 dose of 100 nmol/kg Moreover, separate disposition indices calculated for phase 1 and 2 insulin release, show a different pattern of increase with increasing GLP-1 dose.     

Analysis of proteins associated with growth of Bacteroides ovatus on the branched galactomannan guar gum.

Bacteroides ovatus, a gram-negative obligate anaerobe from the human colon, can ferment the branched galactomannan guar gum. Previously, three enzymes involved in guar gum breakdown were characterized. The expression of these enzymes appeared to be regulated; i.e., specific activities were higher in extracts from bacteria grown on guar gum than in extracts from bacteria grown on the monosaccharide constituents of guar gum, mannose and galactose. In the present study, we used two-dimensional gel analysis to determine the total number of B. ovatus proteins enhanced during growth on guar gum. Twelve soluble proteins and 20 membrane proteins were expressed at higher levels in guar gum-grown cells than in galactose-grown cells. An unexpected finding was that the expression of the two galactomannanases was induced by glucose as well as guar gum. Three other proteins, one membrane protein and two soluble proteins, had this same expression pattern. The remainder of the guar gum-associated proteins seen on two-dimensional gels and the guar gum-associated alpha-galactosidase were induced in cells grown on guar gum but not in cells grown on glucose. Two transposon-generated mutants (M-5 and M-7) that could not grow on guar gum were isolated. Both mutants still expressed the galactomannanases and the alpha-galactosidase. They also still expressed all of the guar gum-associated proteins that could be detected in two-dimensional gels of glucose-grown or galactose-grown cells. A second transposon insertion that suppressed the guar gum-negative phenotype of M-5 was isolated and characterized. The characteristics of this suppressor mutant indicated that the original transposon insertion was probably in a regulatory locus.     

Effect of nutrient ingestion on glucagon-like peptide 1 (7-36 amide) secretion in human type 1 and type 2 diabetes.

Exogenous glucagon-like peptide 1(GLP-1) bioactivity is preserved in type 2 diabetic patients, resulting the peptide administration in a near-normalization of plasma glucose mainly through its insulinotropic effect. GLP-1 also reduces meal-related insulin requirement in type 1 diabetic patients, suggesting an impairment of the entero-insular axis in both diabetic conditions. To investigate this metabolic dysfunction, we evaluated endogenous GLP-1 concentrations, both at fasting and in response to nutrient ingestion, in 16 type 1 diabetic patients (age = 40.5 +/- 14yr, HbA1C = 7.8 +/- 1.5%), 14 type 2 diabetics (age = 56.5 +/- 13yr, HbA1C = 8.1 +/- 1.8%), and 10 matched controls. In postabsorptive state, a mixed breakfast (230 KCal) was administered to all subjects and blood samples were collected for plasma glucose, insulin, C-peptide and GLP-1 determination during the following 3 hours. In normal subjects, the test meal induced a significant increase of GLP-1 (30', 60': p < 0.01), returning the peptide values towards basal concentrations. In type 2 diabetic patients, fasting plasma GLP-1 was similar to controls (102.1 +/- 1.9 vs. 97.3 +/- 4.01 pg/ml), but nutrient ingestion failed to increase plasma peptide levels, which even decreased during the test (p < 0.01). Similarly, no increase in postprandial GLP-1 occurred in type 1 diabetics, in spite of maintained basal peptide secretion (106.5 +/- 1.5 pg/ml). With respect to controls, the test meal induced in both diabetic groups a significant increase in plasma glucagon levels at 60' (p < 0.01). In conclusion, either in condition of insulin resistance or insulin deficiency chronic hyperglycemia, which is a common feature of both metabolic disorders, could induce a progressive desensitization of intestinal L-cells with consequent peptide failure response to specific stimulation.     

Analysis of proteins associated with growth of Bacteroides ovatus on the branched galactomannan guar gum.

Bacteroides ovatus, a gram-negative obligate anaerobe from the human colon, can ferment the branched galactomannan guar gum. Previously, three enzymes involved in guar gum breakdown were characterized. The expression of these enzymes appeared to be regulated; i.e., specific activities were higher in extracts from bacteria grown on guar gum than in extracts from bacteria grown on the monosaccharide constituents of guar gum, mannose and galactose. In the present study, we used two-dimensional gel analysis to determine the total number of B. ovatus proteins enhanced during growth on guar gum. Twelve soluble proteins and 20 membrane proteins were expressed at higher levels in guar gum-grown cells than in galactose-grown cells. An unexpected finding was that the expression of the two galactomannanases was induced by glucose as well as guar gum. Three other proteins, one membrane protein and two soluble proteins, had this same expression pattern. The remainder of the guar gum-associated proteins seen on two-dimensional gels and the guar gum-associated alpha-galactosidase were induced in cells grown on guar gum but not in cells grown on glucose. Two transposon-generated mutants (M-5 and M-7) that could not grow on guar gum were isolated. Both mutants still expressed the galactomannanases and the alpha-galactosidase. They also still expressed all of the guar gum-associated proteins that could be detected in two-dimensional gels of glucose-grown or galactose-grown cells. A second transposon insertion that suppressed the guar gum-negative phenotype of M-5 was isolated and characterized. The characteristics of this suppressor mutant indicated that the original transposon insertion was probably in a regulatory locus.     

Effects of an olive oil-enriched diet on glucagon-like peptide 1 release and intestinal content, plasma insulin concentration, glucose tolerance and pancreatic insulin content in an animal model of type 2 diabetes.

In the light of a recent study conducted in normal rats, the present investigations were aimed at exploring the immediate and long-term effects of an olive oil-enriched diet (OO diet) on GLP-1 release and intestinal content, plasma insulin concentration, glucose tolerance and pancreatic insulin content in adult rats that had been injected with streptozotocin during the neonatal period (STZ rats). The OO diet, when compared to a standard diet, increased the immediate GLP-1 response in meal-trained rats, but decreased GLP-1 content in the intestinal tract after 50 days. Over 50 days, the body weight gain was lower in the rats fed the OO diet compared to standard diet. In the former, however, no improvement of glucose tolerance or insulin response during an oral glucose tolerance test was observed. Thus, a paradoxical lowering of the insulinogenic index, i. e. the paired ratio between plasma insulin and glucose concentration, was recorded during the oral glucose tolerance test in rats fed either standard or OO diet. Moreover, the insulin content of the pancreas was equally low in the STZ rats fed either standard or OO diet. These findings will be discussed in the framework of possible differences in the pathophysiology of B-cell dysfunction in most patients with type-2 diabetes and the present animal model of non-insulin-dependent diabetes.     

Glucose absorption, hormonal release and hepatic metabolism after guar gum ingestion.

Six non-anaesthetized Large White pigs (mean body weight 59 +/- 1.7 kg) were fitted with permanent catheters in the portal vein, the brachiocephalic artery and the right hepatic vein and with electromagnetic flow probes around the portal vein and the hepatic artery. The animals were provided a basal none-fibre diet (diet A) alone or together with 6% guar gum (diet B) or 15% purified cellulose (diet C). The diets were given for 1 week and according to a replicated 3 x 3 latin-square design. On the last day of each adaptation period test meals of 800 g were given prior to blood sampling. The sampling was continued for 8 h. Guar gum strongly reduced the glucose absorption as well as the insulin, gastric inhibitory polypeptide (GIP) and insulin-like growth factor-1 (IGF-1) production. However, the reduction in peripheral blood insulin levels caused by guar gum was not associated with a change in hepatic insulin extraction. IGF-1 appeared to be strongly produced by the gut. The liver had a net uptake of the peptide. Ingestion of guar gum increased the hepatic extraction coefficient of gut produced IGF-1. Guar gum ingestion also appeared to decrease pancreatic glucagon secretion. Cellulose at the level consumed had very little effect on the parameters considered. It is suggested that the modulation of intestinal mechanisms by guar gum was sufficient to mediate the latter internal metabolic effects.     

Effect of polysaccharide structure on mechanical and thermal properties of galactomannan-based films

Films were prepared from guar gum and locust bean gum galactomannans. In addition, enzymatic modification was applied to guar gum to obtain structurally different galactomannans. Cohesive and flexible films were formed from galactomannans plasticized with 20-60% (w/w of polymer) glycerol or sorbitol. Galactomannans with lower galactose content (locust bean gum, modified guar gum) produced films with higher elongation at break and tensile strength. The mechanical properties of films were improved statistically significantly by decreasing the degree of polymerization of guar gum with mannanase treatments (4 h) of 2 and 10 nkat/g, whereas 50 nkat/g produced films with low elongation at break and tensile strength. Galactomannans with approximately 6 galactose units per 10 mannose backbone units resulted in films with 2 peaks in loss modulus spectra, whereas films from galactomannans with approximately 2 galactose groups per 10 mannose units behaved as a single phase in dynamic mechanical analysis.