Glucagon-like peptide-1 response to whey protein is less diminished by dipeptidyl peptidase-4 in comparison with responses to dextrin, a lipid and casein in rats

Although glucose is the best-known nutrient to stimulate glucagon-like peptide-1 (GLP-1) secretion, dietary peptides also potently stimulate GLP-1 secretion. Certain peptide fragments derived from dietary proteins possess dipeptidyl peptidase-4 (DPP-4) inhibitory activity in vitro. Hence, we hypothesised that dietary peptides protect GLP-1 from degradation through attenuating DPP-4 activity in vivo. Here, we compared GLP-1 responses with dietary proteins, a carbohydrate and a lipid (Intralipos) in rats having or not having plasma DPP-4 activity. Plasma GLP-1 concentrations clearly increased by oral administration of whey protein (2-4 g/kg), but not by that of dextrin (2-4 g/kg), in control rats (untreated Sprague-Dawley rats and F344/Jcl rats), having DPP-4 activity. In contrast, dextrin administration increased the plasma GLP-1 concentrations as the whey protein administration did, in rats having reduced or no DPP-4 activity (a DPP-4 inhibitor, sitagliptin-treated Sprague-Dawley rats or DPP-4-deficient F344/DuCrl/Crlj rats). DPP-4 inhibition by sitagliptin treatment also enhanced GLP-1 response to Intralipos, and casein, but the treatment did not further enhance GLP-1 response to whey protein. Intestinal GLP-1 content and gastric emptying rate were not associated with differences in GLP-1 responses to test nutrients. The luminal contents from rats administered whey protein decreased DPP-4 activity in vitro. These results suggest that GLP-1 released by dextrin, Intralipos and casein was immediately degraded by DPP-4, while GLP-1 released by whey protein was less degraded. Our study provides novel in vivo evidence supporting the hypothesis that dietary peptides not only stimulate GLP-1 secretion but also inhibit DPP-4 activity to potentiate GLP-1 response

Combination of alpha-Glycosyl-Isoquercitrin and Soybean Fiber Promotes Quercetin Bioavailability and Glucagon-like Peptide-1 Secretion and Improves Glucose Homeostasis in Rats Fed a High-Fat High-Sucrose Diet

This study examined the effects of a combination of soybean fiber and alpha-glycosyl-isoquercitrin (AGIQ) on improving quercetin bioavailability and glucose metabolism in rats fed an obesogenic diet. For 9 weeks, rats were individually fed a control diet, a high-fat high-sucrose (H) diet, H with soybean fiber (HS), or with AGIQ (HQ), or with both (HSQ). Quercetin derivatives in plasma, feces, urine, and cecal content were quantified by high-performance liquid chromatography to assess the bioavailability of quercetin, and meal tolerance tests were performed to assess postprandial glycemia and glucagon-like peptide-1 (GLP-1) responses. The HSQ group had higher plasma quercetin levels than HQ. The postprandial glycemia was attenuated in the HSQ group when compared to the H group. The basal plasma GLP-1 concentrations positively correlated with plasma quercetin derivative concentrations. Hence, the combination of soybean fiber and AGIQ could be beneficial for reducing the risk of glucose intolerance, possibly involving enhanced quercetin bioavailability and GLP-1 secretion

The Corn Protein, Zein Hydrolysate, Administered into the Ileum Attenuates Hyperglycemia via Its Dual Action on Glucagon-Like Peptide-1 Secretion and Dipeptidyl Peptidase-IV Activity in Rats

We previously showed that a hydrolysate prepared from corn zein [zein hydrolysate (ZeinH)] strongly stimulates glucagons-like peptide-1 (GLP-1) secretion from the murine GLP-1-producing enteroendocrine cell line and in the rat small intestine, especially in the ileum. Here, we investigated whether ZeinH administered into the ileum affects glucose tolerance via stimulating GLP-1 secretion. To observe the effect of luminal ZeinH itself on GLP-1 secretion and glycemia, ip glucose tolerance tests were performed in conscious rats with ileal and jugular catheters, and plasma glucose, insulin, and GLP-1 (total and active) were measured. In addition, plasma dipeptidyl peptidase-IV activities in the ileal vein were measured after the administration of ZeinH into the ileal-ligated loop in anesthetized rats. The ileal administration of ZeinH attenuated the glucose-induced hyperglycemia accompanied by the enhancement of insulin secretion, whereas meat hydrolysate (MHY) neither induced insulin secretion nor attenuated hyperglycemia. The antihyperglycemic effect was also demonstrated by the oral administration of ZeinH. From these results, it was predicted that the GLP-1-releasing potency of ZeinH was higher than that of MHY. However, both peptides induced a similar increase in total GLP-1 concentration after the ileal administration. In contrast, active GLP-1 concentration was increased only in ZeinH-treated rats. In anesthetized rats, ileal administration of ZeinH, but not MHY, decreased plasma dipeptidyl peptidase-IV activity in the ileal vein. These results indicate that the ileal administration of a dietary peptide, ZeinH, has the dual functions of inducing GLP-1 secretion and inhibiting GLP-1 degradation, resulting in the enhancement of insulin secretion and the prevention of hyperglycemia in rat

Enhanced postprandial glucagon-like peptide-1 secretion during obesity development has a protective role against glucose intolerance induction in rats

Glucagon-like peptide-1 (GLP-1) is an incretin hormone that regulates postprandial glycaemic response by enhancing insulin secretion. We previously demonstrated that the postprandial GLP-1 response was enhanced during the development of diet-induced obesity in rats. However, the physiological relevance of the enhanced GLP-1 response remained unclear. We aimed to determine the role of endogenous GLP-1 during obesity development. Male Sprague-Dawley rats were given either a control diet or a high-fat/high-sucrose (HFS, 30 % fat and 40 % sucrose, weight basis) diet with or without continuous administration of the GLP-1 receptor antagonist, exendin (9-39) (Ex9, 100 mu g/d), for 5 weeks. Meal tolerance tests (MTT) were performed to assess postprandial glucose, insulin and GLP-1 responses to a liquid diet administration (15 kcal (63 kJ)/10 ml per kg body weight) every 2 weeks. The AUC of postprandial glucose in the HFS group was similar to the control group in both MTT (P = 0 center dot 9665 and P = 0 center dot 3475, respectively), whereas AUC of postprandial GLP-1 (after 4 weeks,P = 0 center dot 0457) and of insulin (after 2 and 4 weeks, P = 0 center dot 0486 and P = 0 center dot 0110) was higher in the HFS group compared with the control group. In the Ex9 group, AUC of postprandial glucose (P = 0 center dot 0297 and P = 0 center dot 0486) was higher along with a lower insulin response compared with the HFS group (P = 0 center dot 0564 and P = 0 center dot 0281). These results suggest that enhancement of the postprandial GLP-1 response during obesity development has a role in maintaining a normal postprandial glycaemic response. Hence, enhancing endogenous GLP-1 secretion by certain materials could be a potential target for prevention of glucose intolerance

Characterization of Binding Between the Rat Small Intestinal Brush-border Membrane and Dietary Proteins in the Sensory Mechanism of Luminal Dietary Proteins.

Dietary proteins are recognized by the gastrointestinal tract to display physiological functions, however, the sensory mechanism of the intestinal mucosa is not known. We examined binding properties between the rat small intestinal brush-border membrane (BBM) and proteins by using a surface plasmon resonance biosensor. BBM and solubilized BBM prepared from the rat jejunum bound to casein immobilized on the sensor surface, but not to bovine serum albumin. The ileal BBM showed less binding to casein than the jejunal BBM. Solubilized BBM binding to immobilized α-casein was slightly inhibited by aminopeptidase inhibitors, but still more inhibited by addition of casein with the inhibitors. Guanidinated casein inhibited the solubilized BBM binding to α-casein more strongly than casein (casein sodium and α-casein) inhibited. Trypsinization of solubilized BBM abolished its binding activity to α-casein. These results indicate that some membrane protein, but not aminopeptidases, contained in BBM interacts with dietary proteins, and that guanidinated casein has a higher affinity for BBM than intact casein. These binding intensities for proteins were closely correlated to physiological responsiveness, and are possibly involved in a sensory system for dietary protein in the intestine

Continuous feeding of a combined high-fat and high-sucrose diet, rather than an individual high-fat or high-sucrose diet, rapidly enhances the glucagon-like peptide-1 secretory response to meal ingestion in diet-induced obese rats

Objectives: Glucagon-like peptide-1 (GLP-1) is secreted by enteroendocrine L-cells in response to nutrient ingestion. To date, GLP-1 secretion in diet-induced obesity is not well characterized. We aimed to examine GLP-1 secretion in response to meal ingestion during the progression of diet-induced obesity and determine whether a combined high-fat and high-sucrose (HFS) diet, an individual high-fat (HiFat), or a high-sucrose (HiSuc) diet affect adaptive changes in the postprandial GLP-1 response. Methods: Rats were fed a control, HiFat diet (30% weight), HiSuc diet (40% weight), or HFS (30% fat and 40% sucrose) diet for 5 wk. Meal tolerance tests were conducted to determine postprandial glucose, insulin, and GLP-1 responses to standard (control) diet ingestion every 2 wk. Results: After 5 wk, body weight gain of the HiFat (232.3 § 7.8 g; P = 0.021) and HFS groups (228.0 § 7.8; P = 0.039), but not the HiSuc group (220.3 § 7.9; P = 0.244), were significantly higher than that of the control group (200.7 § 5.4 g). In meal tolerance tests after 2 wk, GLP-1 concentration was significantly elevated in the HFS group only (17.2 § 2.6 pM; P < 0.001) in response to meal ingestions, but the HiFat group (16.6 § 3.7 pM; P = 0.156) had a similar response as the HFS group. After 4 wk, GLP-1 concentrations were similarly elevated at 15 min in the HFS (14.1 § 4.4; P = 0.010), HiFat (13.2 § 2.0; P < 0.001), and HiSuc (13.0 § 3.3; P = 0.016) groups, but the HFS (9.8 § 1.0; P = 0.019) and HiFat (8.3 § 1.5; P = 0.010) groups also had significant elevation at 30 min. Conclusions: These results demonstrate that the continuous ingestion of excessive fat and sucrose rapidly enhances the GLP-1 secretory response to luminal nutrients, and the HiFat diet may have a potent effect compared with the HiSuc diet on GLP-1 secretory responses. The increment of postprandial GLP-1 and insulin secretion may have a role in normalizing postprandial glycaemia and slowing the establishment of glucose intolerance

L-homoarginine suppresses exocrine pancreas in rats.

Previously, we found that guanidinated casein, a l-homoarginine-containing protein, was a more potent stimulator of pancreatic enzyme secretion than intact casein in rats. In this study, we examined secretory response and adaptation of the exocrine pancreas to the administration of free l-homoarginine in normal and bile-pancreatic juice (BPJ)-diverted rats. An intraperitoneal injection of l-homoarginine (10mg/rats) produced immediate and transient reduction in pancreatic secretion in BPJ-diverted rats, but not in normal rats. The BPJ-diverted rats were fed with either a 25% casein, 45% casein, or 45% casein diet supplemented with l-homoarginine (19g/kg diet) for 4 days. Feeding of a diet containing l-homoarginine inhibited the pancreatic adaptation induced by the high-protein diet. These results indicate that l-homoarginine has an inhibitory effect on the secretion and production of exocrine pancreatic enzyme in BPJ-diverted rats, and l-homoarginine may have an antagonistic effect on CCK receptors

Postprandial glucagon-like peptide-1 secretion is increased during the progression of glucose intolerance and obesity in high-fat/high-sucrose diet-fed rats

Glucagon-like peptide-1 (GLP-1) is secreted by distal enteroendocrine cells in response to luminal nutrients, and exerts insulinotropic and anorexigenic effects. Although GLP-1 secretory responses under established obese or diabetic conditions have been studied, it has not been investigated whether or how postprandial GLP-1 responses were affected during the progression of diet-induced obesity. In the present study, a meal tolerance test was performed every week in rats fed a high-fat and high-sucrose (HF/HS) diet to evaluate postprandial glycaemic, insulin and GLP-1 responses. In addition, gastric emptying was assessed by the acetaminophen method. After 8 weeks of HF/HS treatment, portal vein and intestinal mucosa were collected to examine GLP-1 production. Postprandial glucose in response to normal meal ingestion was increased in the HF/HS group within 2 weeks, and its elevation gradually returned close to that of the control group until day 50. Slower postprandial gastric emptying was observed in the HF/HS group on days 6, 13 and 34. Postprandial GLP-1 and insulin responses were increased in the HF/HS group at 7 weeks. Higher portal GLP-1 and insulin levels were observed in the HF/HS group, but mucosal gut hormone mRNA levels were unchanged. These results revealed that the postprandial GLP-1 response to meal ingestion is enhanced during the progression of diet-induced glucose intolerance and obesity in rats. The boosted postprandial GLP-1 secretion by chronic HF/HS diet treatment suggests increased sensitivity to luminal nutrients in the gut, and this may slow the establishment of glucose intolerance and obesity

Diet-induced obesity enhances postprandial glucagon-like peptide-1 secretion in Wistar rats, but not in diabetic Goto-Kakizaki rats

Glucagon-like peptide-1 (GLP-1) is postprandially secreted from enteroendocrine L-cells and enhances insulin secretion. Currently, it is still controversial whether postprandial GLP-1 responses are altered in obesity and diabetes. To address the issue and to find out possible factors related, we compared postprandial GLP-1 responses in normal rats and in diabetic rats chronically fed an obesogenic diet. Male Wistar rats and diabetic Goto-Kakizaki (GK) rats were fed either a control diet or a high-fat/high-sucrose (HFS, 30 % fat and 40 % sucrose) diet for 26 weeks. Meal tolerance tests were performed for monitoring postprandial responses after a liquid diet administration (62 center dot 76 kJ/kg body weight) every 4 or 8 weeks. Postprandial glucose, GLP-1 and insulin responses in Wistar rats fed the HFS diet (WH) were higher than Wistar rats fed the control diet (WC). Although GK rats fed the HFS diet (GH) had higher glycaemic responses than GK rats fed the control diet (GC), these groups had similar postprandial GLP-1 and insulin responses throughout the study. Jejunal and ileal GLP-1 contents were increased by the HFS diet only in Wistar rats. Furthermore, mRNA expression levels of fatty acid receptors (Ffar1) in the jejunum were mildly (P = 0 center dot 053) increased by the HFS diet in Wistar rats, but not in GK rats. These results demonstrate that postprandial GLP-1 responses are enhanced under an obesogenic status in normal rats, but not in diabetic rats. Failure of adaptive enhancement of GLP-1 response in GK rats could be partly responsible for the development of glucose intolerance