-Nevertheless-the-3-peptides-were-cosecreted-from-both-perfused-small-intestines-and-colonic-crypt-cultures-in-response-to-a-series-of-metabolite-neuropeptide-and-hormonal-stimuli-u

Importantly, neurotensin acts synergistically, ie, more than additively together with GLP-1 and PYY to decrease palatable food intake and inhibit gastric emptying, but affects glucose homeostasis in a more complex manner. Thus, neurotensin is a major gut hormone deeply integrated with GLP-1 and PYY, which should be taken into account when exploiting the enteroendocrine regulation of metabolism pharmacologically.DPP-4 inhibitors repress NLRP3 inflammasome and interleukin-1beta via GLP-1 receptor in macrophages through protein kinase C pathway.University of Arkansas for Medical Sciences, Little Rock, AR, 72212, USA.BACKGROUND: Anti-atherosclerotic effects of dipeptidyl peptidase-4 (DPP-4) inhibitors have been shown in many studies. Since inflammation and immune response play a key role in atherogenesis, we examined the effect of DPP-4 inhibitors on the expression of nod-like receptor family, pyrin domain containing 3 (NLRP3) Inflammasome and Interleukin-1beta (IL-1β) in human METHODS AND RESULTS: THP-1 macrophages were incubated with oxidized low density lipoprotein (ox-LDL) with or without DPP-4 inhibitors (sitagliptin and NVPDPP728).

The effects of DPP-4 inhibitors on the expression of NLRP3, toll-like receptor 4 (TLR4) and pro-inflammatory cytokine IL-1β were studied. Both DPP-4 inhibitors induced a significant reduction in NLRP3, TLR4 and IL-1β expression; concurrently, there was an increase in glucagon like peptide 1 receptor (GLP-1R) expression. Simultaneously, Pancreatic hormones and other blood sugar regulating drugs -4 inhibitors reduced phosphorylated-PKC, but not PKA, levels. To determine the role of PKC activation in the effects of DPP-4 inhibitors, cells were treated with PMA- which blocked the effect of DPP-4 inhibitors on NLRP3 and IL-1β as well as TLR4 and GLP-1R. Over-expression of GLP-1R in macrophages with its agonist liraglutide also CONCLUSION: DPP-4 inhibitors suppress NLRP3, TLR4 and IL-1β in human macrophages through inhibition of PKC activity. This study provides novel insights into the mechanism of inhibition of inflammatory state and immune response in Late-night-dinner deteriorates postprandial glucose and insulin whereas consuming dinner dividedly ameliorates them in patients with type 2 diabetes: A Medicine, Graduate School of Medical Science, Kyoto, Japan.BACKGROUND AND OBJECTIVES: The aims of this study is to explore the acute effect of consuming dinner at different timing on postprandial glucose and hormone in METHODS AND STUDY DESIGN: Eight patients (age 70±1 years, HbA1c 7±0 %, BMI 23±3, mean±SD) were randomly assigned in this crossover study.

Patients consumed the test meals of dinner at 18:00 on the first day, and dinner at 21:00 or divided dinner (vegetable and rice at 18:00 and vegetable and the main dish at 21:00) on the second or third day. Postprandial glucose, insulin, glucagon, free fatty acid (FFA), active glucagon-like peptide-1 (GLP-1), and active glucose- dependent insulinotropic polypeptide (GIP) concentration after dinner RESULTS: Both incremental area under the curve (IAUC) 2h for glucose and insulin were higher in dinner at 21:00 than those in dinner at 18:00 (IAUC glucose: 449±83 vs 216±43 mmol/L×min, p<01, IAUC insulin:772±104 vs 527±107 μU/mL×min, p<01, mean±SEM). However, in divided dinner both IAUC 4h for glucose and insulin tended to be lower than those of dinner at 21:00 (IAUC glucose: 269±76 mmol/L×min, p=070, IAUC insulin: 552±114 μU/mL×min, p=070). IAUC of active GLP-1 and active GIP demonstrated no difference among different dinner regimen.CONCLUSIONS: Consuming late-night-dinner (21:00) deteriorates postprandial glucose and insulin compared with those of early-evening-dinner (18:00) whereas consuming dinner dividedly ameliorates them.Glucagon-like peptide-1 attenuates tumour necrosis factor-alpha-mediated induction of plasminogen [corrected] activator inhibitor-1 expression.Glucagon-like peptide-1 (GLP-1) has been proposed as a target for treatment of type 2 diabetes.

GLP-1 has also been demonstrated to improve endothelial cell dysfunction in diabetic patients. Elevated plasminogen activator inhibitor type-1 [corrected] (PAI-1) levels have been implicated in endothelial cell dysfunction. glipizide 5 mg of GLP-1 on PAI-1 expression in vascular endothelial cells has not been explored. In a spontaneously transformed human umbilical vein endothelial cell (HUVEC) line, C11-spontaneously transformed HUVEC (STH) and primary HUVEC cells, GLP-1 treatment, in the presence of a dipeptidyl peptidase IV inhibitor, attenuated induction of PAI-1 protein and mRNA expression by tumour necrosis factor-alpha (TNF-alpha). GLP-1 also inhibited the effect of TNF-alpha on a reporter gene construct harbouring the proximal PAI-1 promoter. In addition, GLP-1 attenuated TNF-alpha-mediated induction of Nur77 mRNA and TNF-alpha-mediated binding of nuclear proteins (NPs) to the PAI-1, Nur77, cis-acting response element nerve growth factor induced clone B response element (NBRE). GLP-1 treatment also inhibited TNF-alpha-mediated induction of Akt phosphorylation.