Muramatsu M, Hira T, Mitsunaga A, Sato E, Nakajima S, Kitahara Y, Eto Y, Hara H. Activation of the gut calcium-sensing receptor by peptide agonists reduces rapid elevation of plasma glucose in response to oral glucose load in rats.

Summary Palatinose (isomaltulose), a slowly digested disaccharide, is used as a noncariogenic sugar and as a sucrose substitute in several foods. Because of its ability to lower postprandial glycemia, palatinose may be beneficial as a treatment for impaired glucose metabolism. Glucagon-like peptide-1 (GLP-1) improves glycemia via enhancing pancreatic beta-cell functions. The secretion of GLP-1 is stimulated by sugars, including glucose and artificial sweeteners. In this study, we examined whether palatinose induced GLP-1 secretion in vivo and in vitro. Firstly, portal GLP-1 and glucose were measured after oral administration of palatinose or sucrose in conscious rats. Secondly, portal GLP-1 and glucose were measured after jejunal or ileal administration of each sugar in anesthetized rats. Finally, GLUTag, a murine GLP-1-producing cell line, was exposed to several sugars, including palatinose and sucrose, to observe the direct effect of these sugars on GLP-1 secretion. Compared with sucrose, palatinose enhanced portal GLP-1 level when administered orally in conscious rats. Both palatinose and sucrose induced a significant increase in portal GLP-1 after jejunal or ileal administration of each sugar in anesthetized rats. Ileal administration triggered a greater response than did jejunal administration. Glycemic responses were higher in sucrose-treated rats than in palatinose-treated rats in every experiment. In GLUTag cells, glucose induced a significant increase in GLP-1 secretion, but neither sucrose nor palatinose had an effect. These data demonstrate that luminal palatinose induces GLP-1 secretion in rats. However, it is likely that GLP-1 secretion is triggered mainly by glucose released in the lumen rather than by palatinose itself. Key Words palatinose, isomaltulose, GLP-1, enteroendocrine cells Achieving glycemic control is critical for the prevention and treatment of diabetes and other disorders of glucose metabolism. Inhibitors of ␣ -amylase or ␣ -glucosidase are used to prevent postprandial hyperglycemia by delaying carbohydrate metabolism and thereby reducing glucose absorption from the gut. Delaying carbohydrate metabolism also enhances the secretion of a gut hormone, glucagon-like peptide-1 (GLP-1) ( 1 ). When intact carbohydrates reach the distal small intestine, they are slowly digested there, and glucose is released into the lumen. The middle and distal regions of the small intestine contain "L-type'' enteroendocrine cells that produce GLP-1, glucagon-like peptide-2, and/ or peptide-YY ( 2 ). Luminal glucose is a potent stimulator of GLP-1 secretion from L cells ( 3 , 4 ).GLP-1 has several biological functions: it protects pancreatic ␤ -cells, and it enhances ␤ -cell proliferation and the release of insulin. GLP-1 attenuates hyperglycemia acutely via insulin release; in addition, long-term treatment with GLP-1 or its analogue improves insulinsensitivity in animal models and in human subjects (5)(6)(7)(8). Given the functions of GLP-1 and the location of the cells that secrete it, it is important to ...

Carbohydrate absorption was assessed during acarbose administration to investigate the actions of this drug. In 7 healthy volunteers, breath hydrogen concentration was measured at 15-min intervals after administration of 6 g of lactulose, and continued until 4 h after the breath hydrogen level exceeded its pretreatment value by > or =10 ppm, then the amount of undigested carbohydrate was calculated following administration of various doses of acarbose and Ensure Liquid. Breath hydrogen data were also obtained before and after administration of acarbose to 8 patients with Type 2 diabetes mellitus for 2 and 4 months. After administration of 50 mg of acarbose with 250 ml or 500 ml of Ensure, the mean amount of unabsorbed carbohydrate was 5.3 g and 7.7 g, respectively, while unabsorbed carbohydrate increased to 10.8 g after 100 mg of acarbose with 500 ml of Ensure. In the diabetic patients, breath hydrogen excretion decreased to 31.6% of baseline after 2 months of acarbose administration, indicating decreased carbohydrate malabsorption. Despite this, the haemoglobin A1c level remained stable after 5 months. In conclusion, the extent of carbohydrate malabsorption depended on the acarbose dose and the carbohydrate load. Although carbohydrate malabsorption decreased with continued acarbose administration, the improvement of glycaemic control was maintained.

The interaction of progesterone, testosterone, androsterone, and etiocholanolone with insoluble lipid films (cholesterol and saturated hydrocarbons containing either alcohol, ester, acetamide, phosphate, amine, or carboxyl groups) was studied. In addition to surface pressure and surface potential measurements of the surface films, radioactive tracers were used to measure the concentration of adsorbed steroid in the lipid films. In general, steroids form mixed films with the insoluble lipid films. Compression of the insoluble lipid films to their most condensed state leads to complete ejection of adsorbed steroid from the surface in all cases except with the amine, for which a small amount of steroid is still retained in the surface. Interactions between the steroids and insoluble lipids are primarily due to van der Waals or dispersion forces; there were no significant contributions from dipole-dipole interactions (except possibly with the amine). Specific interactions between cholesterol and the soluble steroids were not observed. Evidence suggests that low steroid concentrations influence structure of lipid films by altering the hydration layer in the surface film. In contrast to a specific site of action, it is proposed that steroid hormones initiate structural changes in a variety of biological sites; this model of steroid action is consistent with the ubiquity of many steroid hormones.

PurposeCalcium‐sensing receptor (CaSR) is widely expressed in various tissues including gastrointestinal tract. However, the role of gut CaSR in digestion/absorption of macronutrients is yet not known. In the present study, we examined whether single oral administration of CaSR agonist peptides affects glycemic response in rats, and also investigated the mechanism by which CaSR agonists modulate the glycemic response.MethodsGlucose tolerance tests were performed under oral or duodenal administration of various CaSR agonist peptides {γGlu‐Cys (γEC), protamine, and poly‐lysine} in conscious rats. Gastric emptying rate was measure by using phenol red method.ResultsOral and duodenal administration of CaSR agonists (γEC, protamine, and poly‐lysine) attenuated the glycemic response under oral glucose tolerance test. Gastric emptying rate was decreased by oral administration of these CaSR agonists. Glucose‐lowering effect of the agonists was partially cancelled by luminal pretreatment with a CaSR inhibitor. In addition, intraperitoneal treatment with 5‐HT3 receptor antagonist partially reversed the glucose‐lowering effect of the agonists.These results demonstrate the activation of gut CaSR by peptide agonists attenuates glycemic response. Involvement of 5‐HT3 receptor and delayed gastric emptying are suggested in the glucose‐lowering effect of these CaSR agonists.