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https://www.readbyqxmd.com/read/28213130/dipeptidyl-peptidase-4-impairs-insulin-signalling-and-promotes-lipid-accumulation-in-hepatocytes
#1
Kerstin Rufinatscha, Bernhard Radlinger, Jochen Dobner, Sabrina Folie, Claudia Bon, Elisabeth Profanter, Claudia Ress, Karin Salzmann, Gabriele Staudacher, Herbert Tilg, Susanne Kaser
Dipeptidyl-peptidase 4 [DPP-4) has evolved into an important target in diabetes therapy due to its role in incretin hormone metabolism. In contrast to its systemic effects, cellular functions of membranous DPP-4 are less clear. Here we studied the role of DPP-4 in hepatic energy metabolism. In order to distinguish systemic from cellular effects we established a cell culture model of DPP-4 knockdown in human hepatoma cell line HepG2. DPP-4 suppression was associated with increased basal glycogen content due to enhanced insulin signalling as shown by increased phosphorylation of insulin-receptor substrate 1 (IRS-1), protein kinase B/Akt and mitogen-activated protein kinases (MAPK)/ERK, respectively...
February 14, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28210986/the-role-of-the-pharmacist-in-managing-type-2-diabetes-with-glucagon-like-peptide-1-receptor-agonists-as-add-on-therapy
#2
REVIEW
Jerry Meece
: The prevalence and associated clinical burden of type 2 diabetes (T2D) is increasing in the USA and other countries. As a consequence, the role of the pharmacist in managing T2D is expanding, and it is becoming increasingly important for pharmacists to have a complete understanding of the disease course and treatment options. Pharmacists have a key role in the use of injectable therapies, including incretin-based treatment with glucagon-like peptide-1 receptor agonists (GLP-1RAs). This article discusses the role of the pharmacist in the management of patients with T2D, particularly with respect to the use of GLP-1RAs to achieve glycemic control...
February 16, 2017: Advances in Therapy
https://www.readbyqxmd.com/read/28209316/intestinal-adaptations-after-bariatric-surgery-consequences-on-glucose-homeostasis
#3
REVIEW
Jean-Baptiste Cavin, André Bado, Maude Le Gall
The gastrointestinal (GI) tract can play a direct role in glucose homeostasis by modulating the digestion and absorption of carbohydrates and by producing the incretin hormones. In recent years, numerous studies have focused on intestinal adaptation following bariatric surgeries. Changes in the number of incretin (glucagon-like peptide 1 and glucose-dependent insulinotropic polypeptide) producing cells have been reported, which could result in the modified hormonal response seen after surgery. In addition, the rate of absorption and the intestinal regions exposed to sugars may affect the time course of appearance of glucose in the blood...
February 10, 2017: Trends in Endocrinology and Metabolism: TEM
https://www.readbyqxmd.com/read/28205322/efficacy-and-safety-of-autoinjected-exenatide-once-weekly-suspension-versus-sitagliptin-or-placebo-with-metformin-in-patients-with-type-2-diabetes-the-duration-neo-2-randomized-clinical-study
#4
Kishore M Gadde, Marion L Vetter, Nayyar Iqbal, Elise Hardy, Peter Öhman
AIMS: Glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors treat type 2 diabetes through incretin-signaling pathways. This study compared the efficacy and safety of the glucagon-like peptide-1 receptor agonist exenatide once-weekly (Miglyol) suspension for autoinjection (QWS-AI) with the dipeptidyl peptidase-4 inhibitor sitagliptin or placebo. MATERIALS AND METHODS: In this open-label, multicenter study of patients with type 2 diabetes who had suboptimal glycemic control on metformin monotherapy, 365 patients were randomized to receive exenatide 2...
February 16, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28204823/incretins-amplify-tnf-%C3%AE-stimulated-il-6-synthesis-in-osteoblasts-suppression-of-the-i%C3%AE%C2%BAb-nf-%C3%AE%C2%BAb-pathway
#5
Kazuhiko Fujita, Haruhiko Tokuda, Naohiro Yamamoto, Shingo Kainuma, Tetsu Kawabata, Go Sakai, Gen Kuroyanagi, Rie Matsushima-Nishiwaki, Atsushi Harada, Osamu Kozawa, Takanobu Otsuka
Incretins including glucagon-like peptide-1 (GLP-1) and glucose‑dependent insulinotropic polypeptide (GIP) secreted from the small intestine after oral food ingestion are currently recognized to stimulate insulin secretion from pancreatic β cells. We previously reported that p70 S6 kinase limits the tumor necrosis factor‑α (TNF‑α)‑stimulated interleukin-6 (IL‑6) synthesis in osteoblast‑like MC3T3‑E1 cells. In the present study, we investigated the effects of incretins on the TNF‑α‑induced IL‑6 synthesis and the underlying mechanism in MC3T3‑E1 cells...
February 15, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28188802/crosstalk-of-metabolic-factors-and-neurogenic-signaling-in-adult-neurogenesis-implication-of-metabolic-regulation-for-mental-and-neurological-diseases
#6
Chong Gao, Qi Wang, Sookja K Chung, Jiangang Shen
Metabolic disorders like diabetes and obesity are commonly companied with neurological diseases and psychiatric disorders. Accumulating evidences indicated that cellular metabolic factors affect adult neurogenesis and have modulating effects on neurodegenerative disorders and psychiatric diseases. Adult neurogenesis contains multiple steps including proliferation of neural stem cells, lineage commitments of neural progenitor cells, maturation into functional neurons, and integration into neuronal network. Many intrinsic and extrinsic factors produced from neural stem/progenitor cells and their microenvironment or neurogenic niche take roles in modulating neurogenesis and contribute to the brain repair and functional recoveries in many neurological diseases and psychiatric disorders...
February 7, 2017: Neurochemistry International
https://www.readbyqxmd.com/read/28188238/vmp1-related-autophagy-induced-by-fructose-rich-diet-in%C3%A2-%C3%AE-cells-it-s-prevention-by-incretins
#7
Bárbara Maiztegui, Verónica Boggio, Carolina Lisi Román, Luis Emilio Flores, Héctor Del Zotto, Alejandro Ropolo, Daniel Grasso, María Inés Vaccaro, Juan José Gagliardino
Aim : To demonstrate the role of autophagy and incretins on fructose-induced alteration in β-cell mass and function. Methods : Normal Wistar rats were fed (3 weeks) with commercial diet without (C) or with 10% fructose in drinking water (F) alone or plus sitagliptin (CS and FS) or exendin-4 (CE and FE). Serum levels of metabolic/endocrine parameters, β-cell mass, morphology/ultrastructure and apoptosis, VMP1 expression and glucose-stimulated insulin secretion (GSIS) were studied. Complementary, islets isolated from normal rats were cultured (3 days) without (C) or with F and F plus exendin-4 (FE) or chloroquine (FCQ)...
February 10, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28185153/role-of-the-gut-on-glucose-homeostasis-lesson-learned-from-metabolic-surgery
#8
REVIEW
V Kamvissi-Lorenz, M Raffaelli, S Bornstein, G Mingrone
PURPOSE OF REVIEW: Bariatric surgery was initially intended to reduce weight, and only subsequently was the remission of type two diabetes (T2D) observed as a collateral event. At the moment, the term "metabolic surgery" is used to underline the fact that this type of surgery is performed specifically to treat diabetes and its metabolic complications, such as hyperlipidemia. RECENT FINDINGS: Randomized, controlled studies have recently supported the use of bariatric surgery, and in particular of Roux-en-Y gastric bypass (RYGB) and biliopancreatic diversion (BPD) as an effective treatment for decompensated T2D...
February 2017: Current Atherosclerosis Reports
https://www.readbyqxmd.com/read/28181363/chronic-liraglutide-therapy-induces-an-enhanced-endogenous-glucagon-like-peptide-1-secretory-response-in-early-type-2-diabetes
#9
Caroline K Kramer, Bernard Zinman, Haysook Choi, Philip W Connelly, Ravi Retnakaran
Sustained exogenous stimulation of a hormone-specific receptor can affect endogenous hormonal regulation. In this context, little is known about the impact of chronic treatment with glucagon-like peptide-1 (GLP-1) agonists on the endogenous GLP-1 response. We therefore evaluated the impact of chronic liraglutide therapy on endogenous GLP-1 and glucose-dependent insulinotropic polypeptide (GIP) response to an oral glucose challenge. A total of 51 people with type 2 diabetes of 2.6 ± 1.9 years' duration were randomized to daily subcutaneous liraglutide or placebo injection and followed for 48 weeks, with an oral glucose tolerance test (OGTT) every 12 weeks...
February 9, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28180919/pathophysiology-of-bone-fragility-in-patients-with-diabetes
#10
REVIEW
Andrea Palermo, Luca D'Onofrio, Raffaella Buzzetti, Silvia Manfrini, Nicola Napoli
It has been well established that bone fragility is one of the chronic complications of diabetes mellitus, and both type 1 and type 2 diabetes are risk factors for fragility fractures. Diabetes may negatively affect bone health by unbalancing several pathways: bone formation, bone resorption, collagen formation, inflammatory cytokine, muscular and incretin system, bone marrow adiposity and calcium metabolism. The purpose of this narrative review is to explore the current understanding of pathophysiological pathways underlying bone fragility in diabetics...
February 8, 2017: Calcified Tissue International
https://www.readbyqxmd.com/read/28180064/dipeptidyl-peptidase-4-inhibitor-treatment-induces-a-greater-increase-in-plasma-levels-of-bioactive-gip-than-glp-1-in-non-diabetic-subjects
#11
Tsuyoshi Yanagimachi, Yukihiro Fujita, Yasutaka Takeda, Jun Honjo, Hidemitsu Sakagami, Hiroya Kitsunai, Yumi Takiyama, Atsuko Abiko, Yuichi Makino, Timothy J Kieffer, Masakazu Haneda
OBJECTIVE: Glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) possess multiple bioactive isoforms that are rendered non-insulinotropic by the enzyme dipeptidyl peptidase-4 (DPP-4). Recently, some ELISA kits have been developed to specifically measure "active" GIP and GLP-1, but it is unclear if these kits can accurately quantify all bioactive forms. Therefore, it remains uncertain to what extent treatment with a DPP-4 inhibitor boosts levels of biologically active GIP and GLP-1...
February 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/28177763/lactoferrin-potentially-facilitates-glucose-regulation-and-enhances-the-incretin-effect
#12
Yuta Maekawa, Akihiko Sugiyama, Takashi Takeuchi
Lactoferrin (Lf) is known for its physiologically pleiotropic properties. In this study, we investigated whether Lf affects glycemic regulation, including glucose absorption from the small intestine. Bovine Lf (bLf, 100 mg/kg body mass) was administered to rats by intraperitoneal injection before intravenous (intravenous glucose tolerance test, IVGTT) or oral glucose administration (oral glucose tolerance test, OGTT). With IVGTT, bLf pretreatment had no significant effect on plasma levels of glucose or insulin...
February 2017: Biochemistry and Cell Biology, Biochimie et Biologie Cellulaire
https://www.readbyqxmd.com/read/28166771/glycemic-insulinemic-and-incretin-responses-after-oral-trehalose-ingestion-in-healthy-subjects
#13
Chiyo Yoshizane, Akiko Mizote, Mika Yamada, Norie Arai, Shigeyuki Arai, Kazuhiko Maruta, Hitoshi Mitsuzumi, Toshio Ariyasu, Shimpei Ushio, Shigeharu Fukuda
BACKGROUND: Trehalose is hydrolyzed by a specific intestinal brush-border disaccharidase (trehalase) into two glucose molecules. In animal studies, trehalose has been shown to prevent adipocyte hypertrophy and mitigate insulin resistance in mice fed a high-fat diet. Recently, we found that trehalose improved glucose tolerance in human subjects. However, the underlying metabolic responses after trehalose ingestion in humans are not well understood. Therefore, we examined the glycemic, insulinemic and incretin responses after trehalose ingestion in healthy Japanese volunteers...
February 6, 2017: Nutrition Journal
https://www.readbyqxmd.com/read/28153578/improving-drug-like-properties-of-insulin-and-glp-1-via-molecule-design-and-formulation-and-improving-diabetes-management-with-device-drug-delivery
#14
REVIEW
Sergei Pechenov, Himanshu Bhattacharjee, Daniel Yin, Sachin Mittal, Anand Subramony
There is an increased incidence of diabetes worldwide. The discovery of insulin revolutionized the management of diabetes, the revelation of glucagon-like peptide -1 (GLP-1) and introduction of GLP-1 mimetics to clinical practice was another breakthrough. Continued translational research resulted in better understanding of diabetes, which, in combination with cutting-edge biology, chemistry, and pharmaceutical tools, have allowed for the development of safer, more effective and convenient insulins and GLP-1s...
January 30, 2017: Advanced Drug Delivery Reviews
https://www.readbyqxmd.com/read/28148253/cardiovascular-safety-of-non-insulin-pharmacotherapy-for-type-2-diabetes
#15
REVIEW
James Xu, Rohan Rajaratnam
Patients with type 2 diabetes mellitus have a twofold increased risk of cardiovascular mortality compared with non-diabetic individuals. There is a growing awareness that glycemic efficacy of anti-diabetic drugs does not necessarily translate to cardiovascular safety. Over the past few years, there has been a number of trials evaluating the cardiovascular effects of anti-diabetic drugs. In this review, we seek to examine the cardiovascular safety of these agents in major published trials. Metformin has with-stood the test of time and remains the initial drug of choice...
February 2, 2017: Cardiovascular Diabetology
https://www.readbyqxmd.com/read/28126633/differential-impact-of-glucose-administered-intravenously-or-orally-on-bone-turnover-markers-in-healthy-male-subjects
#16
Sidse Westberg-Rasmussen, Jakob Starup-Linde, Kjeld Hermansen, Jens Juul Holst, Bolette Hartmann, Peter Vestergaard, Søren Gregersen
BACKGROUND: Patients with type-1 (T1D) and type-2 diabetes mellitus (T2D) have an increased risk of hip fracture. The underlying mechanisms may involve disturbances in the incretin hormones. Our aim was to clarify if glucose administration i.e. orally or intravenously differentially affects bone turnover markers in healthy males. METHODS: 12 healthy males were included in a cross-over study consisting of three tests following an 8hour fast. First, an oral glucose tolerance test (OGTT) was performed...
January 23, 2017: Bone
https://www.readbyqxmd.com/read/28119531/changes-in-glycemia-insulin-and-gut-hormone-responses-to-a-slowly-ingested-solid-low-carbohydrate-mixed-meal-after-laparoscopic-gastric-bypass-or-band-surgery
#17
J C Bunt, R Blackstone, M S Thearle, K L Vinales, S Votruba, J Krakoff
OBJECTIVE: To evaluate early changes in glycemia, insulin physiology and gut hormone responses to an easily tolerated and slowly ingested solid, low-carbohydrate mixed meal (MMT) following adjustable gastric banding (LAGB) or Roux-en-Y gastric bypass (RYGB) surgery. SUBJECTS/METHODS: This was a prospective non-randomized study. Plasma glucose, insulin and c-peptide (to estimate hepatic insulin extraction; %HIE), incretins (GIP, aGLP-1) and pancreatic polypeptide (PP) responses to the MMT were measured at 4-8 weeks before and after surgery in obese, metabolically healthy patients (RYGB=10F or LAGB=7F/1M)...
January 25, 2017: International Journal of Obesity: Journal of the International Association for the Study of Obesity
https://www.readbyqxmd.com/read/28106217/flavanol-concentrations-do-not-predict-dipeptidyl-peptidase-iv-inhibitory-activities-of-four-cocoas-with-different-processing-histories
#18
Caroline M Ryan, Weslie Khoo, Amanda C Stewart, Sean F O'Keefe, Joshua D Lambert, Andrew P Neilson
Cocoa and its constituent bioactives (particularly flavanols) have reported anti-diabetic and anti-obesity activities. One potential mechanism of action is inhibition of dipeptidyl peptidase-IV (DPP4), the enzyme that inactivates incretin hormones such as glucagon-like peptide-1 and gastric inhibitory peptide. The objective of this study was to determine the DPP4 inhibitory activities of cocoas with different processing histories, and identify processing factors and bioactive compounds that predict DPP4 inhibition...
January 20, 2017: Food & Function
https://www.readbyqxmd.com/read/28105345/attenuation-by-incretins-of-thyroid-hormone-stimulated-osteocalcin-synthesis-in-osteoblasts
#19
Shingo Kainuma, Haruhiko Tokuda, Kazuhiko Fujita, Tetsu Kawabata, Go Sakai, Rie Matsushima-Nishiwaki, Atsushi Harada, Osamu Kozawa, Takanobu Otsuka
Incretins, the polypeptide hormone glucose- dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) secreted from the small intestine after nutrient ingestion, are generally known to stimulate insulin secretion from pancreatic β-cells. We previously demonstrated that triiodothyronine (T3) stimulates osteocalcin synthesis at least in part through p38 mitogen-activated protein kinase in osteoblast-like MC3T3-E1 cells. In the present study, we investigated the effects of GIP and GLP-1 on T3-stimulated osteocalcin synthesis and the mechanism of action involved in MC3T3-E1 cells...
December 2016: Biomedical Reports
https://www.readbyqxmd.com/read/28094469/immunohistochemical-assessment-of-glucagon-like-peptide-1-receptor-glp-1r-expression-in-the-pancreas-of-patients-with-type-2-diabetes
#20
Rikke Kaae Kirk, Charles Pyke, Matthias G von Herrath, Jane Preuss Hasselby, Lars Pedersen, Pia Gottrup Mortensen, Lotte Bjerre Knudsen, Ken Coppieters
Glucagon-like peptide-1 (GLP-1) is an incretin hormone which stimulates insulin release and inhibits glucagon secretion from the pancreas in a glucose-dependent manner. Incretin-based therapies, consisting of GLP-1 receptor (GLP-1R) agonists and dipeptidyl peptidase-4 (DPP-4) inhibitors, are used for the treatment of T2D. Immunohistochemical studies for GLP-1R expression have previously been hampered by the use of unspecific polyclonal antibodies. This study used a new monoclonal antibody to assess GLP-1R expression in pancreatic tissue from 23 patients with T2D, including 7 with a DPP-4 inhibitor and 1 with a GLP-1R agonist treatment history...
January 17, 2017: Diabetes, Obesity & Metabolism
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