Thirty days of resveratrol supplementation does not affect postprandial incretin hormone responses, but suppresses postprandial glucagon in obese subjects.

AIMS: Resveratrol, a natural polyphenolic compound produced by various plants (e.g. red grapes) and found in red wine, has glucose-lowering effects in humans and rodent models of obesity and/or diabetes. The mechanisms behind these effects have been suggested to include resveratrol-induced secretion of the gut incretin hormone glucagon-like peptide-1. We investigated postprandial incretin hormone and glucagon responses in obese human subjects before and after 30 days of resveratrol supplementation. METHODS: Postprandial plasma responses of the incretin hormones glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide and glucagon were evaluated in 10 obese men [subjects characteristics (mean ± standard error of the mean): age 52 ± 2 years; BMI 32 ± 1 kg/m(2), fasting plasma glucose 5.5 ± 0.1 mmol/l] who had been given a dietary supplement of resveratrol (Resvida(®) 150 mg/day) or placebo for 30 days in a randomized, double-blind, crossover design with a 4-week washout period. At the end of each intervention period a standardized meal test (without co-administration of resveratrol) was performed. RESULTS: Resveratrol supplementation had no impact on fasting plasma concentrations or postprandial plasma responses (area under curve values) of glucose-dependent insulinotropic polypeptide (11.2 ± 2.1 vs. 11.8 ± 2.2 pmol/l, P = 0.87; 17.0 ± 2.2 vs. 14.8 ± 1.6 min × nmol/l, P = 0.20) or glucagon-like peptide-1 (15.4 ± 1.0 vs. 15.2 ± 0.9 pmol/l, P = 0.84; 5.6 ± 0.4 vs. 5.7 ± 0.3 min × nmol/l, P = 0.73). Resveratrol supplementation significantly suppressed postprandial glucagon responses (4.4 ± 0.4 vs. 3.9 ± 0.4 min × nmol/l, P = 0.01) without affecting fasting glucagon levels (15.2 ± 2.2 vs. 14.5 ± 1.5 pmol/l, P = 0.56). CONCLUSIONS: Our data suggest that 30 days of resveratrol supplementation does not affect fasting or postprandial incretin hormone plasma levels in obese humans, but suppresses postprandial glucagon responses.

Randomised controlled trial of colostrum to improve intestinal function in patients with short bowel syndrome.

BACKGROUND/OBJECTIVES: Colostrum is rich in immunoregulatory, antimicrobial and trophic components supporting intestinal development and function in newborns. We assessed whether bovine colostrum could enhance intestinal adaptation and function in adult short bowel syndrome (SBS) patients. SUBJECTS/METHODS: Twelve SBS patients in this randomised cross-over study received 4 weeks oral supplement of bovine colostrum or an iso-energetic and iso-proteinaceous control (2.4 MJ/d, 500 ml/day) separated by a 4-week washout period. Patients were admitted four times for 72-h periods of fluid, electrolyte and nutrient balance studies. Meals, faeces and urine were weighed, and energy, macronutrient and electrolyte contents were analysed to calculate net nutrient uptake. Body composition was measured by dual-energy X-ray absorptiometry scans, and functional tests of handgrip strength and lung functions were performed. Eight patients completed the study and were included in the analysis. RESULTS: Both supplements (colostrum and control) not only increased protein (0.96 ± 0.42 MJ/d, P=0.004 1.03 ± 0.44 MJ/d, P=0.003) and energy (1.46 ± 1.02 MJ/d, P=0.005, 1.76 ± 1.46 MJ/d, P=0.01) absorption but also absolute faecal wet weight excretions (231 ± 248 g/d, P=0.002, 319 ± 299 g/d, P=0.03), compared with baseline measurements. Both supplements improved handgrip strength (P=0.03) while only the control supplement increased lean body mass (1.12 ± 1.33 kg, P<0.049). Colostrum was not found to be superior to the control. CONCLUSION: Intake of high-protein milk supplements increased net nutrient absorption for adult SBS patients, but at the expense of increased diarrhoea. Despite high contents of bioactive factors, colostrum did not significantly improve intestinal absorption, body composition or functional tests compared with the control.

Effects of different fractions of whey protein on postprandial lipid and hormone responses in type 2 diabetes.

BACKGROUND/OBJECTIVES: Exacerbated postprandial lipid responses are associated with an increased cardiovascular risk. Dietary proteins influence postprandial lipemia differently, and whey protein has a preferential lipid-lowering effect. We compared the effects of different whey protein fractions on postprandial lipid and hormone responses added to a high-fat meal in type 2 diabetic subjects. SUBJECTS/METHODS: A total of 12 type 2 diabetic subjects ingested four isocaloric test meals in randomized order. The test meals contained 100 g of butter and 45 g of carbohydrate in combination with 45 g of whey isolate (iso-meal), whey hydrolysate (hydro-meal), α-lactalbumin enhanced whey (lac-meal) or caseinoglycomacropeptide enhanced whey (CGMP-meal). Plasma concentrations of triglyceride, retinyl palmitate, free fatty acid, insulin, glucose, glucagon, glucagon-like peptide 1 and glucose-dependent insulinotropic peptide were measured before and at regular intervals until 8-h postprandially. RESULTS: We found no statistical significant differences between meals on our primary variable triglyceride. The retinyl palmitate response was higher after the hydro-meal than after the iso- and lac-meal in the chylomicron-rich fraction (P=0.008) while no significant differences were found in the chylomicron-poor fraction. The hydro- and iso-meal produced a higher insulin response compared with the lac- and CGMP-meal (P<0.001). Otherwise no significant differences in the hormone responses were found in the incremental area under the curve over the 480-min period. CONCLUSIONS: A supplement of four different whey protein fractions to a fat-rich meal had similar effects on postprandial triglyceride responses in type 2 diabetic subjects. Whey isolate and whey hydrolysate caused a higher insulin response.

Chenodeoxycholic acid reduces intestinal permeability in newly weaned piglets.

Piglets are highly susceptible to gut health-related problems. Intravenously administered chenodeoxycholic acid (CDCA) affects gut health mediated through glucagon-like peptide 2 (GLP-2). To test whether CDCA is a suitable feed additive for improving gut health, a trial was performed with newly weaned (21 d) piglets offered a diet with or without 60 mg CDCA/kg feed (n = 24/treatment). Upon weaning, piglets were fasted for 16 h and then intragastrically dosed with 20 g test feed in 40 g water. Subsequently, a jugular blood sample was taken on 45, 90, 135, or 180 min for analysis of GLP-2, peptide YY (PYY), and glucose. Afterwards, piglets were offered the experimental diets ad libitum. On days 3.5, 7.5, and 10.5 after weaning, serum responses to an intragastric dose of lactulose and Co-EDTA were tested at 2 h after dosing in 8 piglets per treatment. Immediately thereafter, piglets were euthanized, intestines were harvested, and permeability was measured ex vivo using the everted gut sac technique with 4 kDa fluorescein isothiocyanato (FITC)-dextran as marker at 25, 50, and 75% of the length of the small intestine. Dietary CDCA did not affect (P > 0.05) ADFI, ADG, G:F, blood glucose, and plasma GLP-2 and PYY. Serum cobalt and lactulose at day 10.5 tended to be lower in CDCA pigs compared with control pigs. Serum cobalt and lactulose concentrations were positively correlated (r = 0.67; P < 0.01). In conclusion, CDCA tended to reduce intestinal permeability at 10.5 d after weaning when fed to newly weaned piglets, implying that CDCA deserves further study as a means for improving intestinal health. The positive correlation found between Co-EDTA and lactulose indicates that both marker molecules measure similar change in permeability.

Effect of method of delivery of sodium butyrate on rumen development in newborn calves.

The effect of sodium butyrate (SB) supplementation in milk replacer (MR) or in starter mixture (SM) or in both MR and SM on performance, selected blood parameters, and rumen development in newborn calves was determined. Twenty-eight male calves with a mean age of 5 (±1) d were randomly allocated into 1 of 4 groups (7 animals per group) and fed (1) MR and SM, both without SB (MR(-) and SM(-), respectively); (2) MR(-) and SM supplemented with SB encapsulated within a triglyceride matrix (SM(+), 0.6% as fed; 30:70 butyrate-to-triglyceride matrix); (3) MR supplemented with crystalline SB (MR(+), 0.3% as fed) and SM(-); or (4) MR(+) and SM(+). The MR was offered in an amount equal to 10% of the initial body weight (BW) of each calf. The SM was blended with whole corn grain (50/50; wt/wt) and offered ad libitum as a starter diet (0.3% encapsulated-within-triglyceride matrix SB when SM(+) was fed) from the first day of the trial. Calves were slaughtered at d 21 of a trial (mean age 26±1 d). Addition of SB into MR (MR(+)) positively affected BW and average daily gain, tended to decrease the number of days with electrolyte therapies from d 0 to 7, and tended to positively affect fecal consistency from d 8 to 14 of the trial. Inclusion of SB into SM (SM(+)) increased starter diet intake from d 15 to 21, decreased the number of days with scours, and tended to decrease the number of days with electrolyte therapies in the whole trial period. Both MR(+) and SM(+) increased plasma glucose in the whole trial period and MR(+) increased total serum protein at d 14. The SM(+) increased plasma glucagon-like peptide-2 (GLP-2) concentration at d 7 of the trial when compared with the concentration at d 0. Both MR(+) and SM(+) increased reticulorumen weight and papillae length and width. Based on these results, it can be concluded that addition of SB in MR positively affected BW gain, health, and some metabolic intermediates of calves and it stimulated rumen development indirectly, whereas SB supplementation in SM stimulated rumen development directly. Addition of SB both in MR and SM could be recommended for rearing calves.

Glucagon antagonism as a potential therapeutic target in type 2 diabetes.

Glucagon is a hormone secreted from the alpha cells of the pancreatic islets. Through its effect on hepatic glucose production (HGP), glucagon plays a central role in the regulation of glucose homeostasis. In patients with type 2 diabetes mellitus (T2DM), abnormal regulation of glucagon secretion has been implicated in the development of fasting and postprandial hyperglycaemia. Therefore, new therapeutic agents based on antagonizing glucagon action, and hence blockade of glucagon-induced HGP, could be effective in lowering both fasting and postprandial hyperglycaemia in patients with T2DM. This review focuses on the mechanism of action, safety and efficacy of glucagon antagonists in the treatment of T2DM and discusses the challenges associated with this new potential antidiabetic treatment modality.

Effect of sodium butyrate supplementation in milk replacer and starter diet on rumen development in calves.

Rumen development is an important factor determining early solid feed intake and performance in cattle. A popular trend towards early weaning of newborn dairy calves necessitated looking for ways of accelerating the gastrointestinal tract (GIT) development. The present study aimed to determine the effect of sodium butyrate (NaB) supplementation in milk replacer and starter diet on rumen development in rearing calves. Fourteen bull calves (5-day-old) were randomly allocated to two groups: Control (C) and NaB. The later received 0.3 % NaB in milk replacer and starter diet. Animals were in experiment up to age of 26 days. Addition of NaB to milk replacer and starter diet had no effect on daily growth rate, but reduced the weight loss observed in C calves in first 11 days of age. Additionally, the NaB calves weighed more at the end of the study and tended to have higher growth rate in the whole trial period (P<0.15). The NaB calves showed a tendency toward higher reticulorumen weight (P=0.13) and higher reticulorumen weight expressed as a percent of whole stomach weight (P=0.02) as compared to control. Histometry analysis indicated larger rumen papillae length and width (P<0.01) in NaB group, and no change in muscle layer thickness, as compared to control. Plasma glucagon-like peptide-2 relative increase was higher in NaB group than in C group, and may be involved in rumen development. In conclusion, supplementation of the diet (milk replacer and starter diet) with NaB may enhance rumen development in neonatal calves.

Effects of soy supplementation on blood lipids and arterial function in hypercholesterolaemic subjects.

BACKGROUND: Studies on soy supplementation suggest a cardioprotective potential. OBJECTIVE: To examine the effects on LDL cholesterol and arterial function as a result of dietary enrichment with soy supplementation. DESIGN: A Randomized, double blind, parallel intervention trial. SETTING: Department of Endocrinology and Metabolism C, Aarhus University Hospital, and Department of Human Nutrition, The Royal Veterinary and Agricultural University, Denmark. SUBJECTS: In all, 100 hypercholesterolaemic but otherwise healthy subjects were included in the study of which 89 completed it. INTERVENTIONS: Subjects were randomly assigned to 24 weeks of daily intake of either a soy supplement, Abalon (30 g soy protein, 9 g cotyledon fibre and 100 mg isoflavones) or placebo (30 g of casein). The soy supplement and placebo were provided in two sachets daily that were stirred in water. Fasting plasma lipids, TNF-alpha, homocysteine, insulin sensitivity, homeostasis model assessment (HOMA-IR), serum insulin, serum glucose, blood pressure as well as Glucagon-like peptide 1 (GLP-1), glucose-dependent insulinotropic peptide (GIP) and plasma lipids to a fat-rich meal were recorded before and after the intervention. In a sub study in 32 subjects, arterial dilatory capacity, compliance, and distensibility were recorded before and after the intervention. RESULTS: In the main study, no difference in fasting plasma lipid levels or insulin sensitivity was found between soy-based supplement and placebo. A significant postprandial increase in GIP to the meal test was observed in the soy group (P < 0.05). In a substudy, no difference between the groups in changes in flow-mediated vasodilatation (P = 0.84) was detected, while the soy supplementation caused a reduction in LDL and total cholesterol. CONCLUSIONS: No significant effects on blood lipids were observed in the main study to a soy supplementation in hypercholesterolaemic subjects after 24 weeks. In the substudy, the soy supplementation, however, reduced LDL and total cholesterol but did not influence markers of arterial function.

Glucagon-like peptide 2 improves nutrient absorption and nutritional status in short-bowel patients with no colon.

BACKGROUND & AIMS: Glucagon-like peptide 2 (GLP-2) is intestinotrophic, antisecretory, and transit-modulating in rodents, and it is mainly secreted from the intestinal mucosa of the terminal ileum and colon after food ingestion. We assessed the effect of GLP-2 on the gastrointestinal function in patients without a terminal ileum and colon who have functional short-bowel syndrome with severe malabsorption of wet weight (>1.5 kg/day) and energy (>2.3 MJ/day) and no postprandial secretion of GLP-2. METHODS: Balance studies were performed before and after treatment with GLP-2, 400 microg subcutaneously twice a day for 35 days, in 8 patients (4-17 years from last bowel resection; 6 with Crohn's disease). Four patients received home parenteral nutrition (mean residual jejunum, 83 cm), and 4 did not (mean ileum resection, 106 cm). Biopsy specimens were taken from jejunal/ileal stomas, transit was measured by scintigraphy, and body composition was measured by dual-energy x-ray absorptiometry. RESULTS: Treatment with GLP-2 improved the intestinal absorption of energy 3.5% +/- 4.0% (mean +/- SD) from 49.9% to 53.4% (P = 0.04), wet weight 11% +/- 12% from 25% to 36% (P = 0.04), and nitrogen 4.7% +/- 5.4% from 47.4% to 52.1% (P = 0.04). Body weight increased 1.2 +/- 1.0 kg (P = 0.01), lean body mass increased 2.9 +/- 1.9 kg (P = 0.004), fat mass decreased 1.8 +/- 1.3 kg (P = 0.007), and 24-hour urine creatinine excretion increased (P = 0.02). The time to 50% gastric emptying of solids increased 30 +/- 16 minutes from 89 to 119 minutes (P < 0.05). Small bowel transit time was not changed. Crypt depth and villus height were increased in 5 and 6 patients, respectively. CONCLUSIONS: Treatment with GLP-2 improves intestinal absorption and nutritional status in short-bowel patients with impaired postprandial GLP-2 secretion in whom the terminal ileum and the colon have been resected.

Influence of acarbose on post-prandial insulin requirements in patients with Type 1 diabetes.

The primary objective of this double-blind, placebo-controlled, randomised cross-over study was to investigate the influence of acarbose on insulin requirement in patients with Type 1 diabetes (T1DM) following a standardised meal. In addition, the study assessed the effects of acarbose on post-prandial triglyceride, glucagon and gastrointestinal peptide levels, gastric emptying, and oxidative glucose metabolism. Following normalisation of their blood glucose, 10 patients received a standardised meal together with acarbose (100 mg) or placebo. Each patient was evaluated twice (separated by 10+/-3 days), and the cross-over study design ensured that they received both acarbose and placebo. The insulin requirement for maintenance of normoglycaemia was assessed using a closed-loop insulin infusion system (artificial pancreas, Biostator). Acarbose produced a statistically significant reduction in mean insulin requirement over a 3-hr period following the meal compared with placebo (5171.7+/-2282.6 mU vs 8074.5+/-3045.4 mU; p=0.003). The level of blood glucose control over the same period was similar in the two groups. Gastric inhibitory polypeptide levels also showed a statistically significant decrease with acarbose treatment compared with placebo for AUC (area under the curve; p=0.006) and Cmax (maximum plasma concentration; p=0.022), but not tmax (time to reach Cmax from the start of the standardised meal; p>0.05). Analysis of the other efficacy parameters revealed no statistically significant differences between acarbose treatment and placebo (p>0.05). These results indicate that acarbose decreases insulin requirement in patients with T1DM without affecting gastric emptying.

Differential effects of saturated and monounsaturated fatty acids on postprandial lipemia and incretin responses in healthy subjects.

BACKGROUND: Elevations of postprandial triacylglycerol-rich plasma lipoproteins and suppressions of HDL-cholesterol concentrations are considered potentially atherogenic. Long-term studies have shown beneficial effects of monounsaturated fatty acids (eg, oleic acid) on fasting lipid and lipoprotein concentrations in humans. A direct stimulatory effect of oleic acid on the secretion of glucagon-like peptide 1 (GLP-1) was shown in animal studies. OBJECTIVE: We compared the postprandial responses of glucose, insulin, fatty acids, triacylglycerol, gastric inhibitory polypeptide (GIP), and GLP-1 to test meals rich in saturated and monounsaturated fatty acids. DESIGN: Ten young, lean, healthy persons ingested 3 meals: an energy-free soup consumed with 50 g carbohydrate (control meal), the control meal plus 100 g butter, and the control meal plus 80 g olive oil. Triacylglycerol and retinyl palmitate responses were measured in total plasma, in a chylomicron-rich fraction, and in a chylomicron-poor fraction. RESULTS: No significant differences in glucose, insulin, or fatty acid responses to the 2 fat-rich meals were seen. Plasma triacylglycerol responses were highest after the butter meal, with chylomicron triacylglycerol rising 2.5-5-fold. Retinyl palmitate responses were higher and more prolonged after the butter meal than after the control and olive oil meals, whereas both postprandial HDL-cholesterol concentrations and GLP-1 and GIP responses were higher after the olive oil meal than after the butter meal. CONCLUSIONS: Olive oil induced lower triacylglycerol concentrations and higher HDL-cholesterol concentrations than butter, without eliciting differences in concentrations of glucose, insulin, or fatty acids. Furthermore, olive oil induced higher concentrations of GLP-1 and GIP than did butter, which may point to a relation between fatty acid composition, incretin responses, and triacylglycerol metabolism in the postprandial phase.

Prolonged and enhanced secretion of glucagon-like peptide 1 (7-36 amide) after oral sucrose due to alpha-glucosidase inhibition (acarbose) in Type 2 diabetic patients.

GLP-1, an incretin hormone of the enteroinsular axis with insulinotropic and glucagonostatic activity, is secreted after nutrient ingestion. GLP-1 is mainly produced by intestinal L-cells in the lower gastrointestinal tract (GIT); simple carbohydrates are absorbed in the upper GIT and alpha-glucosidase inhibition leads to augmented and prolonged GLP-1 release in normal subjects. In a cross-over study, 100 mg acarbose or placebo was administered simultaneously with 100 g sucrose to 11 hyperglycaemic Type 2 diabetic patients poorly controlled with diet and sulphonylureas. Plasma levels of GLP-1, insulin, C-peptide, glugacon, GIP, glucose and H2-exhalation were measured over 6 h. Differences in the integrated responses over the observation period were evaluated by repeated measurement analysis of variance with fasting values used as covariates. With acarbose, sucrose reached the colon 60-90 min after ingestion as indicated by a significant increment in breath hydrogen exhalation (p = 0.005). After an early GLP-1 increment 15 min after sucrose under both conditions, GLP-1 release was prolonged in the acarbose group (p = 0.001; significant from 210 to 360 min.). Initially (0-150 min), glucose (p = 0.001), insulin (p = 0.001), and GIP (p < 0.001) were suppressed by acarbose, whereas later there were no significant differences. Glucagon levels were higher with acarbose in the last 3 h of the 6 h observation period (p = 0.02). We conclude that in hyperglycaemic Type 2 diabetic patients, ingestion of acarbose with a sucrose load leads to elevated and prolonged GLP-1 release.

Dipeptidyl peptidase IV inhibition potentiates the insulinotropic effect of glucagon-like peptide 1 in the anesthetized pig.

Glucagon-like peptide 1 (GLP-1) has been proposed as a new therapeutic agent in the management of diabetes because of its glucose-dependent stimulation of insulin secretion, but this is limited by its rapid degradation in vivo by dipeptidyl peptidase IV (DPP IV). In nonfasted anesthetized pigs, valine-pyrrolidide (a stable and selective inhibitor of DPP IV), at a dose that reduced plasma DPP IV activity by more than 90%, increased both the amount of intact GLP-1 in the basal state (from 5 +/- 1 to 18 +/- 7 pmol/l; P < 0.05) and the proportion remaining undegraded during an infusion (from 21.0 +/- 1.3 to 102.3 +/- 4.5%; P < 0.0001). This was associated with a prolonged plasma half-life for the intact peptide (from 1.0 +/- 0.1 to 3.2 +/- 0.2 min; P < 0.0005). In the basal (nonfasted) state, valine-pyrrolidide potentiated the effect of intravenous GLP-1 on the incremental area under the curve (AUC) for glucose (-0.50 +/- 0.91 to -2.83 +/- 0.59 20 min x mmol x l(-1); P < 0.05) and insulin (23.8 +/- 30.5 to 332.5 +/- 99.6 20 min x pmol x l(-1); P < 0.05). When an intravenous glucose load was given during the GLP-1 infusion, valine-pyrrolidide augmented the insulin response (AUC, 2,086.2 +/- 600.9 to 6,247.0 +/- 1443.9 40 min x pmol x l(-1); P < 0.05). These results suggest that by reducing GLP-1 degradation, DPP IV inhibition potentiates the insulinotropic effect of GLP-1 and may, therefore, be a viable approach to the management of diabetes.

Glucagon-like peptide 1 and its potential in the treatment of non-insulin-dependent diabetes mellitus.

Studies examining small groups of type 2-(NIDDM) diabetic patients have shown the potential of glucagon-like peptide 1 (GLP-1) to normalize fasting hyperglycaemia. Patient characteristics determining the size of the effect have not been reported. Therefore, the results of four studies were analysed. Exogenous GLP-1 was administered i.v. or s.c. in 37 type 2-diabetic patients, age 60 +/- 8 years; BMI 28.2 +/- 5.3 kg/m2; HbA1c 10.6 +/- 1.6%; diabetes duration 10 +/- 6 years, treatment with sulfonylureas, n = 33, metformin, n = 11, acarbose, n = 3. Results were analysed using repeated measures analysis of variance and multiple regression analysis. Exogenous GLP-1 lowered fasting plasma glucose within 4-5 h from 12.8 +/- 2.5 to 5.3 +/- 1.3 mmol/l (placebo: 12.8 +/- 2.3 to 10.0 +/- 2.2; p < 0.0001 for the interaction of treatment and time). Only fasting glycaemia (p = 0.0085) and the route (i.v. vs. s.c.; p = 0.05), but not gender, age, BMI, HbA1c, diabetes duration, treatment with sulfonylureas, metformin or acarbose, were significant predictors of the plasma glucose concentrations reached after the administration of GLP-1 (variation: 3.4-8.5 mmol/l). In conclusion, GLP-1 is able to normalize plasma glucose in all type 2-diabetic patients studied. This analysis underlines the great therapeutic potential of GLP-1.

Acetylation of or beta-cyclodextrin addition to potato beneficial effect on glucose metabolism and appetite sensations.

Functional foods are gaining more and more interest from health scientists. One way to improve the nutritional properties of foods may be to modify the starch component, often included to stabilize the food product. In this study two chemically modified starches-a 1-2% acetylated potato starch and a starch enriched with 2% beta-cyclodextrin-and a native, unmodified potato starch (control) were investigated with regard to 6-h energy expenditure, substrate metabolism, hormone concentrations, and subjective appetite sensations. Subjects were 11 healthy, normal-weight, young men. The starch (50 g) was prepared as a pudding with fruit sauce and whipped cream (3180 kJ, 49% of energy from carbohydrate, and 40% of energy from fat). The meal was given in the morning after a 2-d carbohydrate-rich, weight-maintenance diet. After the modified-starch meals, response patterns for plasma glucose (P < 0.01), insulin (P < 0.05); gastric inhibitory polypeptide (P < 0.05), subjective satiety (P < 0.05), and fullness (P = 0.06) were significantly different from response patterns after the meal with the control starch. Thus, a flattening of the glucose curve, a lower insulin and gastric inhibitory polypeptide response, and higher fullness ratings were observed after the meal with the beta-cyclodextrin starch. Satiety ratings were higher after both meals with modified starch than after the meal with the control starch. In conclusion, a minor modification insulinemic (1-2%) of native potato starch improved the glycemia, insulinemic, and satiating properties of a meal. This was especially true for the beta-cyclodextrin-enriched starch. Slower gastric-emptying rate or delayed intestinal absorption of the modified starch may explain the observed differences.

[Leptin--a new weight-loss agent?]. / Leptin--vorherres slankemiddel?

The relatively constant level of body fat in the adult mammal is explained by the lipostat theory as follows: A factor is released from adipose tissue in amounts that reflect total body fat content. This factor is then registered by the hypothalamic centres that regulate appetite. The theory has gained particular support from parabiotic experiments in genetically fat mice, amongst whom the so-called ob/ob mice appear to produce too little of the factor, whilst signal transduction to the satiety centre appears to be defective in the so-called db/db mice. The two genetic defects have recently been clarified, and it has been shown that the normal ob gene nodes for a protein called leptin. Leptin is released from adipose tissue, and its plasma concentration reflects total body fat. The normal db-gene codes for a hypothalamic receptor for leptin. These crucial discoveries have greatly supported the correctness of the lipostat theory. At present, extensive investigations of the roles of leptin and the leptin receptor in human adiposity are in progress.

Glucagon-like peptide I receptors in the subfornical organ and the area postrema are accessible to circulating glucagon-like peptide I.

The intestinal incretin hormone glucagon-like peptide I (GLP-I) inhibits gastric motility and secretion in normal, but not in vagotomized subjects, pointing to a centrally mediated effect. Therefore, our aim was to study the availability of rat brain GLP-I receptors to peripherally injected 125I-labeled GLP-I. The specificity of the binding was tested by co-injection of excess amounts of unlabeled GLP-I. Using light microscopical autoradiography of rat brain sections, we found specific 125I-GLP-I binding exclusively in the subfornical organ and the area postrema. This binding was abolished when an excess amount of unlabeled GLP-I was co-injected with the labeled GLP-I. We conclude that cells in the subfornical organ and the area postrema could be responsive to blood-borne GLP-I. The observed binding of peripherally administered GLP-I to the subfornical organ and the area postrema, which both have close neuroanatomical connections with hypothalamic areas involved in water and appetite homeostasis, is consistent with the potential roles of circulating GLP-I in the central regulation of appetite and autonomic functions.

Gene expression of pituitary adenylate cyclase activating polypeptide (PACAP) in the rat hypothalamus.

Pituitary adenylate cyclase activating polypeptide (PACAP) isolated from ovine hypothalamus is considered to be a member of the vasoactive intestinal peptide/glucagon/secretin/growth hormone-releasing hormone family of peptides. Two forms of PACAP, PACAP38 and PACAP27, have been demonstrated in the rat hypothalamus. The PACAP precursor contains another peptide called PACAP-related peptide (PRP), but so far no information on this peptide in tissue exists. We have developed three radioimmunoassays specific for PACAP38, PACAP27 and PRP and demonstrate that all three preproPACAP peptides are expressed in the rat hypothalamus, the PACAP38/PACAP27 ratio being around 60 and the PACAP38/PRP ratio being around 10. HPLC analysis of hypothalamic extract showed that PACAP38 and PACAP27 are found in only one form corresponding to the respective synthetic peptides, whereas PRP eluted in two peaks, the predominant form corresponding to synthetic PRP1-29. The cellular distribution of PACAP38, PACAP27, and PRP and corresponding mRNA in the hypothalamus was determined with immunohistochemistry and in situ hybridization histochemistry. PACAP- and PRP-immunoreactive neuronal perikarya were observed in the medial parvocellular part of the paraventricular nucleus (PVN) in colchicine pretreated rats. Some cell bodies of magnocellular variety were found in the PVN. PACAP mRNA containing cells were observed in moderate numbers in the same parts of the paraventricular nucleus. PACAP- and PRP immunoreactive fibres and varicosities were distributed in the PVN and in the periventricular nucleus. These data show that PACAP38, PACAP27 and PRP are expressed in the parvocellular part of the PVN, implying roles as hypothalamic regulatory peptides.

Distribution and characterization of different molecular products of pro-somatostatin in the hypothalamus and posterior pituitary lobe of the Mongolian gerbil (Meriones unguiculatus).

Antisera raised against various synthetic peptide fragments of the pro-somatostatin molecule were used to visualize immunohistochemically the distributions of different pro-somatostatin fragments in the hypothalamus and posterior pituitary of the Mongolian gerbil. To define the nature of the immunoreactive somatostatin-related molecular forms, gel chromatography combined with radioimmunoassays of hypothalamic and posterior pituitary extracts was performed. Within the hypothalamus, only trace amounts of somatostatin-28 and somatostatin-28(1-12) were present, whereas pro-somatostatin(1-76), pro-somatostatin(1-64), and somatostatin-14 peptides were present in equimolar amounts. In contrast, the posterior pituitary lobe contained equal amounts of somatostatin-14, somatostatin-28, and somatostatin-28(1-12) but no pro-somatostatin(1-76), indicating that pro-somatostatin is further processed during the axonal flow to posterior pituitary nerve terminals. The gel chromatographic data were further substantiated by immunohistochemical data. Thus, perikarya containing all of these five immunoreactivities were strictly confined to the periventricular area and parvocellular subset of the paraventricular nucleus. However, the number of somatostatin-28- and somatostatin-28(1-12)-immunoreactive perikarya was approximately 20% of the number of somatostatin-14- and pro-somatostatin(1-64)-immunoreactive cells. In other hypothalamic areas only somatostatin-14 and pro-somatostatin(1-64) immunoreactivities were detectable in cell bodies. These cell bodies were encountered in the organum vasculosum laminae terminalis; the suprachiasmatic, ventromedial, arcuate, perifornical, and posterior hypothalamic nuclei; and the median preoptic and retrochiasmatic areas. In situ hybridization histochemistry revealed that the cellular distribution of pro-somatostatin mRNA corresponds to that of somatostatin-14 and pro-somatostatin immunoreactivity, suggesting that the immunoreactive material observed within the cell bodies is synthetized there and that the differences in density of immunoreactivities may be explained by intracellular processing of pro-somatostatin. Somatostatinergic nerve fibers and terminals in hypothalamic areas and the posterior pituitary lobe were immunoreactive to all of the employed antisera. From the present results, obvious differences between intrahypothalamic and hypothalamo-pituitary somatostatinergic neurons emerge. Within hypothalamic neurons not projecting to the median eminence and the posterior pituitary lobe, pro-somatostatin is posttranslationally processed in the cell body predominantly into pro-somatostatin(1-64) and somatostatin-14. Otherwise, within periventricular neurons projecting to the median eminence and the posterior pituitary lobe, pro-somatostatin is posttranslationally processed during the axonal flow into pro-somatostatin(1-64), somatostatin-14, somatostatin-28, and somatostatin-28(1-12).