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The present study aims mainly at measuring, in normal rats, the GLP-1 response to oral intake of an olive oil-enriched diet (OO), and at assessing the long-term effects of such a diet on the GLP-1 content of the intestinal tract, as well as the plasma D-glucose, insulin, and GLP-1 pattern during an oral glucose tolerance test. In meal-trained rats, the mean increment in plasma GLP-1 concentration at min 10 and 20 was 1.39 +/- 0.23 ng/mL higher (p < 0.001) in the rats given access to the OO diet rather than control diet. Relative to the initial value (d 0), the gain in body weight at d 50 was also higher in the animals fed the OO rather than control diet. At d 50, the GLP-1 content of the jejunum, ileum, colon, and cecum were not significantly different in the two groups of rats. At d 19 and 36, the increment in both plasma insulin concentration and paired ratio between plasma insulin and D-glucose concentrations were again higher, during an oral glucose tolerance test conducted in overnight fasted animals, in the rats otherwise fed the OO, as distinct from control, diet. The intake of an olive oil-enriched diet thus increases, in normal rats, GLP-1 release, this coinciding during long-term exposure to the OO diet with higher body weight gain, increased secretory response of insulin-producing cells to oral glucose administration, and, after 36 d, improved glucose tolerance.

Objective: To assess whether oral D-fructose modifies the plasma D-glucose and insulin responses to oral D-glucose administration in normal rats., Design: Oral D-glucose (1.7, 3.5, 6.9 or 13.9 micromol/g body weight), D-fructose (6.9 micromol/g), both D-glucose and D-fructose (1.7 or 3.5 micromol/g of each hexose) or sucrose (3.7 micromol/g) were administered intragastrically to overnight fasted rats and the plasma concentration of D-glucose, D-fructose and insulin measured over the ensuing 120 minutes. Control experiments were conducted after oral administration of H(2)O or saline., Results: The administration of D-fructose, given as the free hexose or as sucrose, instead of augmenting the plasma D-glucose concentration evoked by the concomitant administration of D-glucose, tended both to improve the insulin response of the pancreatic B-cell and to minimize hyperglycemia, when compared to the results of experiments including the administration of equimolar amounts of D-glucose alone. For instance, the area under the plasma D-glucose curve was comparable in the rats receiving both D-glucose and D-fructose (3.5 micromol/g of each hexose) and the rats receiving only D-glucose (3.5 micromol/g), averaging respectively 836 +/- 32 and 850 +/- 34 mM . min each. Likewise, the paired ratio between the areas under the plasma insulin and D-glucose curves, when corrected for the threshold concentration for the insulinotropic action of the hexose (2.05 +/- 0.10 mM), averaged 44.3 +/- 3.0 nmol/mol in the 16 rats receiving D-fructose alone, sucrose alone or both D-glucose and D-fructose, as compared to 37.7 +/- 2.9 nmol/mol in the 22 rats receiving increasing amounts of D-glucose alone., Conclusions: The intake of D-fructose, as the free hexose or as sucrose, favours D-glucose homeostasis. This is likely to be attributable to the reciprocal effects of the aldose and ketose upon their respective phosphorylation by glucokinase in both hepatocytes and insulin-producing pancreatic islet cells.

Glucagon-like peptide-1 (GLP-1) is the most insulinogenic of the glucagon-like peptides secreted mainly by L cells in the small and large intestine in response to the ingestion of nutrients. It binds to a specific GLP-1 receptor (GLP-1R) on beta-cells and can increase islet neogenesis and beta-cell mass. It is not clear whether the transmission of information from the gut to islet beta-cells by messengers such as GLP-1 is different in individuals who develop autoimmune diabetes. In the present study the expression of bioactive GLP-1 protein in the gut and its receptor in the pancreas was examined in diabetes-prone BioBreeding (BBdp) rats in the period before overt diabetes and in age-matched control, non-diabetes-prone BB (BBc) rats. An N-terminal directed antibody specific for the bioactive forms of GLP-1 (GLP-1(7-37) and GLP-1(7-36amide)) was used to mea-sure GLP-1 by radioimmunoassay in proximal, median, and distal gut. Pancreas GLP-1R area fraction, GLP-1R gene expression, and insulin content were analyzed, as were plasma GLP-1, glucose, and insulin. The concentration of GLP-1 protein in the jejunum and ileum of BBdp rats was lower than in BBc rats. Although these animals maintained normal blood glucose, there was impaired pancreatic endocrine function, characterized by low baseline insulin concentration in plasma and pancreas. GLP-1R mRNA expression was threefold less in islets isolated from BBdp rats, and GLP-1R+ islet area fraction in pancreas sections was decreased. When injected iv with GLP-1, BBdp rats displayed lower second-phase insulin response (and insulin/glucose ratios) compared with BBc rats. Thus, young BBdp rats displayed decreased concentrations of bioactive GLP-1 in jejunum and ileum, reduced GLP-1R in islets, and lower second-phase insulin response to iv GLP-1 than controls. The decrease in insulinogenic and islet beta-cell mass-promoting signal from GLP-1 in BBdp rats may contribute to impaired glucoregulation and ineffective maintenance of normal islet mass that shifts islet homeostasis in favor of development of diabetes.

Glucagon-like peptide 1 (GLP-1) controls glucose metabolism in extrapancreatic tissues through receptors other than the pancreatic cAMP-linked GLP-1 receptor; also, GLP-1 induces an insulin- and PTH-independent bone anabolic action in insulin-resistant and type-2 diabetic rats. Here we searched for the presence and characteristics of GLP-1 receptors in osteoblastic MC3T3-E1 cells. [125I]-GLP-1 specific binding to MC3T3-E1 cells was time- and temperature-dependent, reaching maximal value at 30 min at 25°C; in these conditions, [125I]-GLP-1 binding was dissociable, and displaced by GLP-1, partially by GLP-2, but not by exendin-4 (Ex-4), exendin-9 (Ex-9), glucagon or insulin; Scatchard analysis of the unlabeled GLP-1 data showed high and low affinity binding sites; cross-linking of GLP-1 binding revealed an estimated 70 kDa band, almost undetectable in the presence of 10-6 M GLP-1. GLP-1, Ex-9, insulin or glucagon failed to modify cellular cAMP content, while GLP-2 and Ex-4 increased it. However, GLP-1 induced an immediate hydrolysis of glycosylphosphatidylinositols (GPIs) generating short-lived inositolphosphoglycans (IPGs), and an increase in phosphatidylinositol-3 kinase (PI3K) and mitogen activated protein kinase (MAPK) activities; Ex-4 also affected GPIs, but its action was delayed with respect to that of GLP-1. This incretin was found to decrease Runx2 but increased osteocalcin gene expression, without affecting that of osteoprotegerin or the canonical Wnt pathway activity in MC3T3-E1 cells which do not express the pancreatic GLP-1 receptor. Our data demonstrate for the first time that GLP-1 can directly and functionally interact with osteoblastic cells, possibly through a GPI/IPG-coupled receptor. J. Cell. Physiol. 225: 585–592, 2010. © 2010 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]