The secondary objective was to evaluate the effects of pasireotide on oral glucose absorption.RESULTS: Pasireotide treatment resulted in significant decreases in insulin AUC0-180 min during both the hyperglycemic clamp test (-77%; P < 01 in both dose groups) and the OGTT (-61%; P < 01 in both dose groups). Suppression of glucagon levels was less pronounced. No significant changes in hepatic or peripheral insulin sensitivity were found during the hyperinsulinemic-euglycemic clamp test. Additionally, significant increases in glucose AUC₀₋₁₈₀ min (+67%) and decreases in AUC₀₋₁₈₀ min glucagon-like peptide-1 (-46%) and glucose-dependent insulinotropic polypeptide levels (-69%) were observed during the OGTT. No dose dependency or unexpected adverse events were observed.

CONCLUSIONS: Pasireotide-associated hyperglycemia is related to decreases in insulin secretion and incretin hormone responses, without changes in hepatic/peripheral insulin sensitivity.The glucagon-like peptide-1 receptor agonist liraglutide improves hypoxia-induced pulmonary hypertension in mice partly via normalization of The glucagon-like peptide-1 receptor (GLP-1R) agonist liraglutide is an incretin hormone mimetic used in the treatment of diabetes. However, the effects of liraglutide on pulmonary hypertension (PH) and pulmonary endothelin (ET) system are unknown. Eight-week-old C57BL6/J mice were injected liraglutide or vehicle for 5 weeks. One week after injection, the mice were exposed to either room air systolic pressure (RVSP) was significantly higher in hypoxia + vehicle group than in normoxia + vehicle group. ET-1 mRNA expression in the lungs was comparable among all the groups. ET(B) mRNA and glp 1 agonist in the lungs was significantly lower in hypoxia + vehicle group than in normoxia + vehicle group.

The above changes were normalized by liraglutide treatment. The expression of phospho-eNOS and phospho-AMPK proteins in the lungs was significantly higher in hypoxia + liraglutide group than in normoxia + vehicle group. We demonstrated for the first time that liraglutide effectively improved RVSP and RV hypertrophy in hypoxia-induced PH mice by activating eNOS through normalization of impaired ET(B) pathway and augmentation of AMPK pathway. Therefore, GLP-1R agonists can be promising therapeutic agents for PH.Activity-induced GLP-1 release in lean and obese subjects.and Toxicology Research Institute Maastricht (NUTRIM), 6200 MD Maastricht, The The aim of the study was to determine whether physical activity stimulates GLP-1 release on the short-term in normal weight and in obese subjects compared to rest and, furthermore, whether modest weight loss affects GLP-1 release or sensitivity in the obese. Normal weight (n=28; 12 males, 16 females; BMI 22+/-1; age 35+/-12), as well as obese subjects (n=27; 21 males, 6 females; BMI 30+/-2; age 47+/-116) were tested in a resting and a physical activity condition.

Obese subjects were matched over two groups for a weight loss period of 3 months. After weight loss, the tests were repeated. The area under the curve (AUC pmol/lxmin) for GLP-1 concentrations was significantly increased in the physical activity condition compared to rest in lean subjects (P=05) as well as in the obese subjects after weight loss (P<05), but not in the obese subjects before weight loss. Physical activity-stimulated GLP-1 release in lean and obese subjects after a weight loss period supports the idea of a neuroendocrine loop in addition to distal-intestinal stimulation of GLP-1 release. Modest weight loss might be effective for increasing GLP-1 sensitivity Glucagon-like peptide-1 induces cell proliferation and pancreatic-duodenum homeobox-1 expression and increases endocrine cell mass in the pancreas of old, Glucose homeostasis in mammals is maintained by insulin secretion from the beta-cells of the islets of Langerhans. Type 2 diabetes results either from primary beta-cell failure alone and/or a failure to secrete enough insulin to overcome insulin resistance. Here, we show that continuous infusion of glucagon-like peptide-1 (7-36) (GLP-1; an insulinotropic agent), to young and old animals, had effects on the beta-cell of the pancreas other than simply on the insulin secretory apparatus.

Our previous studies on a rodent model of glucose intolerance, the aging Wistar rat, show that a plateau in islet size, insulin content, and beta-cell mass is reached at 13 months, despite a continuing increase in body weight. Continuous sc infusion of GLP-1 (1 pM/kg x min), over 5 days, resulted in normal glucose tolerance. Our current results in both young and old rats demonstrate that treatment caused an up-regulation of pancreatic-duodenum homeobox-1 (PDX-1) expression in islets and total pancreas, induced pancreatic cell proliferation, and beta-cell neogenesis. The effects on levels of PDX-1 messenger RNA were abrogated by simultaneous infusion of Exendin (9-39), a specific antagonist of GLP-1. PDX- glipizide side effects increased 4-fold in whole pancreata and 6-fold in islets in response to treatment. Beta-cell mass increased to 7 +/- 08 from 48 +/- 08 mg, treated vs. control, respectively, P < 02.

Total pancreatic insulin content also increased from 05 +/- 02 to 12 +/- 01 microg/mg total pancreatic protein.