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Petr Ježek, Martin Jabůrek, Blanka Holendová, Lydie Plecitá-Hlavatá
Fatty acid (FA)-stimulated insulin secretion (FASIS) is reviewed here in contrast to type 2 diabetes etiology, resulting from FA overload, oxidative stress, intermediate hyperinsulinemia, and inflammation, all converging into insulin resistance. Focusing on pancreatic islet β-cells, we compare the physiological FA roles with the pathological ones. Considering FAs not as mere amplifiers of glucose-stimulated insulin secretion (GSIS), but as parallel insulin granule exocytosis inductors, partly independent of the KATP channel closure, we describe the FA initiating roles in the prediabetic state that is induced by retardations in the glycerol-3-phosphate (glucose)-promoted glycerol/FA cycle and by the impaired GPR40/FFA1 (free FA1) receptor pathway, specifically in its amplification by the redox-activated mitochondrial phospholipase, iPLA2γ...
June 19, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Miguel F Herrera, Eduardo García-García, Juan F Arellano-Ramos, Miguel Agustín Madero, Jorge Antonio Aldrete-Velasco, Juan Antonio López Corvalá
INTRODUCTION: Metabolic surgery (MS) can be a useful therapeutic strategy in patients with type 2 diabetes (DM2) and obesity. OBJECTIVE: To define the place of MS within DM2 treatment in Mexico. METHODS: A committee of experts consisting of internists and surgeons representing the leading Mexican associations involved in the field was created. Each one responded to a specific question regarding mechanisms involved in controlling DM2, surgical procedures, and the indications and contraindications for MS...
June 18, 2018: Obesity Surgery
Mahip K Verma, Rajan Goel, Nandakumar Krishnadas, Kumar V S Nemmani
Incretin hormones, glucose-dependent insulinotropic polypeptide (GIP) and glucagon like peptide (GLP-1) exert pleiotropic effects on the endocrine pancreas and nervous system. Expression of GIP and GIP receptor (GIPR) in neurons, their roles in neurogenesis, synaptic plasticity, neurotransmission and neuromodulation, uniquely positions GIPR for therapeutic applications in neurodegenerative disorders. GIP analogues acting as GIPR agonists attenuate neurobehavioral and neuropathological sequelae of neurodegenerative disorders in preclinical models, e...
June 18, 2018: Expert Opinion on Therapeutic Targets
K S Weber, K Straßburger, M Fritsch, A Bierwagen, C Koliaki, E Phielix, G Pacini, J-H Hwang, D F Markgraf, V Burkart, K Müssig, J Szendroedi, M Roden
AIM: Type 2 diabetes (T2D) alters glucagon, glucagon-like peptide (GLP)-1, glucose-dependent insulinotropic polypeptide (GIP) and hepatic energy metabolism, yet the possible relationships remain unclear. METHODS: In this observational study, lean insulin-sensitive control subjects (BMI: 23.2±1.5kg/m2 ), age-matched insulin-resistant obese subjects (BMI: 34.3±1.7kg/m2 ) and similarly obese elderly T2D patients (BMI: 32.0±2.4kg/m2 ) underwent mixed-meal tolerance tests (MMTTs), and assessment of hepatic γATP, inorganic phosphate (Pi ) and lipids using 31 P/1 H magnetic resonance spectroscopy...
June 2, 2018: Diabetes & Metabolism
Dan Kawamori
Glucagon secreted by pancreatic α-cells plays pivotal roles in the systemic energy homeostasis mainly by regulating systemic glucose mobilization together with another important metabolic hormone, insulin. Recent application of the incretin-based therapies to clinical diabetes refocused on the central roles of glucagon in the development of diabetic hyperglycemia. This revival of glucagon also enhanced the progress of basic research in α-cell biology, as targeting glucagon is now expected to be the next therapeutic approach in diabetes treatment...
June 15, 2018: Journal of Diabetes Investigation
Henry Reyer, Michael Oster, Elizabeth Magowan, Eduard Murani, Helga Sauerwein, Dirk Dannenberger, Björn Kuhla, Siriluck Ponsuksili, Klaus Wimmers
Feed efficiency (FE) is a measure of the rate between feed intake and body weight gain and is subject to constant progress in pigs, based on extensive performance tests and analyses of physiological parameters. However, endocrine regulatory circuits which comprise the sensation and perception of intrinsic requirements and appropriate systemic responses have not yet been fully elucidated. It is hypothesized that the gut-brain-axis, which is a network of hierarchical anterior regulatory tissues, contributes largely to variations in FE...
June 15, 2018: Physiological Genomics
Megan E Capozzi, Richard D DiMarchi, Matthias H Tschöp, Brian Finan, Jonathan E Campbell
Glucagon-like peptide-1 (GLP-1) receptor agonists have been efficacious for the treatment of type 2 diabetes due to their ability to reduce weight and attenuate hyperglycemia. However, the activity of GLP-1R-directed strategies is sub-maximal, and the only potent, sustainable treatment for metabolic dysfunction is bariatric surgery, necessitating the development of novel therapeutics. GLP-1 is structurally related to glucagon and glucose-dependent insulinotropic peptide (GIP), allowing for the development of intermixed, unimolecular peptides with activity at each of their respective receptors...
June 13, 2018: Endocrine Reviews
Ana I Duarte, Marie Sjögren, Maria S Santos, Catarina R Oliveira, Paula I Moreira, Maria Björkqvist
Neuronal loss alongside altered energy metabolism, are key features of Huntington's disease (HD) pathology. The orexigenic gut-peptide hormone ghrelin is known to stimulate appetite and affect whole body energy metabolism. Liraglutide is an efficient anti-type 2 diabetes incretin drug, with neuroprotective effects alongside anorectic properties. Combining liraglutide with the orexigenic peptide ghrelin may potentially promote brain/cognitive function in HD. The R6/2 mouse model of HD exhibits progressive central pathology, weight loss, deranged glucose metabolism, skeletal muscle atrophy and altered body composition...
June 12, 2018: Scientific Reports
Yuya Tsurutani, Kazuki Nakai, Kosuke Inoue, Azuma Kosuke, Sei Mukai, Seitaro Maruyama, Takashi Iizuka, Yoko Matsuzawa, Jun Saito, Masao Omura, Tetsuo Nishikawa
This randomized study assessed the efficacy of ipragliflozin compared with sitagliptin in 124 Japanese patients with type 2 diabetes. Sodium-glucose cotransporter 2 inhibitor and incretin-related agent naïve patients were randomly assigned to receive additional 50 mg ipragliflozin or sitagliptin. The primary endpoint was the proportion of patients with more than 0.5% decrease in HbA1c without body weight gain at 12 weeks. For secondary endpoints, we measured several biomarkers related to metabolic changes...
June 12, 2018: Diabetes, Obesity & Metabolism
Zahra Fallah, Awat Feizi, Mahin Hashemipour, Roya Kelishadi
Background: This study, for the first time, aimed to assess the effects of fermented camel milk (FCM) on glycemic and inflammatory parameters related to metabolic syndrome (MetS), an aggregation of cardiometabolic risk factors, in adolescents. Materials and Methods: In a double-blind, randomized crossover trial, overweight/obese adolescents (fulfilling MetS criteria, aged 11-18 years) were randomly assigned to receive FCM 250 cc per day for an 8-week period, a 4-week washout, and then diluted cow's yogurt (DCY) 250 cc/day for another 8-week period, or the reverse sequence...
2018: Journal of Research in Medical Sciences: the Official Journal of Isfahan University of Medical Sciences
Florian Kahles, Ana Liberman, Constantin Halim, Matthias Rau, Julia Möllmann, Robert Werner Mertens, Marcia Rückbeil, Irmgard Diepolder, Benedikt Walla, Sebastian Diebold, Mathias Burgmaier, Corinna Lebherz, Nikolaus Marx, Michael Lehrke
OBJECTIVE: The incretin hormones GLP-1 (glucagon-like peptide-1) and GIP (glucose-dependent insulinotropic peptide) are secreted by the gut after food intake leading to pancreatic insulin secretion and glucose lowering. Beyond its role in glucose control, GLP-1 was found in mice and men to beneficially modulate the process of atherosclerosis, which has been linked to improved cardiovascular outcome of patients with diabetes at high cardiovascular risk treated with GLP-1 receptor agonists...
May 23, 2018: Molecular Metabolism
Badhma Valaiyapathi, Barbara Gower, Ambika P Ashraf
BACKGROUND: The prevalence of type 2 diabetes (DM) in children is disturbingly increasing in parallel with increasing childhood obesity. Better knowledge regarding the pathophysiology of type 2 DM in children is paramount to devise an effective management plan. OBJECTIVE: Discuss the pathophysiology of type 2 DM in children and adolescents Methods and results: This is a comprehensive review of the literature on this topic. Type 2 DM in childhood is viewed as a continuum of insulin resistance (IR) which is determined by an underlying genetic predisposition, intrauterine environment, excessive food consumption, continued rapid weight gain, and poor lifestyle...
June 7, 2018: Current Diabetes Reviews
Weijia Xie, Xiaoxiao Song, Zhenjie Liu
Dipeptidyl peptidase 4 (DPP-4) inhibitor is a novel group of medicine employed in type 2 diabetes mellitus (T2DM),which improves meal stimulated insulin secretion by protecting glucagon-like peptide-1 (GLP-1) and glucose dependent insulinotropic polypeptide (GIP) from enzymatic degradation. Cardiovascular diseases are serious complications and leading causes of mortality among individuals with diabetes mellitus. Glycemic control per se seems to fail in preventing the progression of diabetic cardiovascular complications...
June 4, 2018: Vascular Pharmacology
Jia Nie, Chao Sun, Zhijie Chang, Nicolas Musi, Yuguang Shi
Rho GDP-dissociation inhibitor (GDIα) inhibits glucose-stimulated insulin secretion (GSIS) in part by locking Rho GTPases in an inactive GDP-bound form. The onset of GSIS causes phosphorylation of GDIα at Ser174, a critical inhibitory site for GDIα, leading to the release of Rho GTPases and their subsequent activation. However, the kinase regulator(s) that catalyzes the phosphorylation of GDIα in islet β-cells remains elusive. We propose that SAD-A, a member of AMPK-related kinases that promotes GSIS as an effector kinase for incretin signaling, interact with and inhibit GDIα through phosphorylation of Ser174 during the onset GSIS from islet β-cells...
June 4, 2018: Endocrinology
Michael Doumas, Κonstantinos Imprialos, Konstantinos Stavropoulos, Andromachi Reklou, Alexandros Sachinidis, Vasilios G Athyros
BACKGROUND: The treatment of type 2 diabetes mellitus (T2DM) is complex; only few patients successfully attain glycemic targets with monotherapy, most requiring drug combination therapy. METHODS: The goal of this review was to identify in PubMed the complimentary ways of action leading to clinical benefit (in lowering HbA1c, body weight, renal, and cardiac risk factors and events) of the combination of sodium glucose cotransporter 2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1 RA)...
June 3, 2018: Current Pharmaceutical Design
Markus Mühlemann, Daniela Zdzieblo, Alexandra Friedrich, Constantin Berger, Christoph Otto, Heike Walles, Hermann Koepsell, Marco Metzger
OBJECTIVES: Glycemic control by medical treatment represents one therapeutic strategy for diabetic patients. The Na+-d-glucose cotransporter 1 (SGLT1) is currently of high interest in this context. SGLT1 is known to mediate glucose absorption and incretin secretion in the small intestine. Recently, inhibition of SGLT1 function was shown to improve postprandial hyperglycemia. In view of the lately demonstrated SGLT1 expression in pancreatic islets, we investigated if loss of SGLT1 affects islet morphology and function...
May 23, 2018: Molecular Metabolism
Maria Daniela Garcia-Castillo, Daniel J-F Chinnapen, Yvonne M Te Welscher, Rodrigo J Gonzalez, Samir Softic, Michele Pacheco, Randall J Mrsny, C Ronald Kahn, Ulrich H von Andrian, Jesper Lau, Bradley L Pentelute, Wayne I Lencer
Transport of biologically active molecules across tight epithelial barriers is a major challenge preventing therapeutic peptides from oral drug delivery. Here, we identify a set of synthetic glycosphingolipids that harness the endogenous process of intracellular lipid-sorting to enable mucosal absorption of the incretin hormone GLP-1. Peptide cargoes covalently fused to glycosphingolipids with ceramide domains containing C6:0 or smaller fatty acids were transported with 20-100-fold greater efficiency across epithelial barriers in vitro and in vivo...
May 31, 2018: ELife
Kirnjot Mehat, Christopher Peter Corpe
PURPOSE OF REVIEW: The current review summarizes and discusses current research on differences elicited between sugars and nonnutritive sweeteners via sugar-sensing pathways. RECENT FINDINGS: Sugars, sweeteners, and sweetening agents are all perceived as sweet tasting because of their ability to bind to the type 1 taste receptor family of sweet taste receptors in the oral cavity. The ability of a wide variety of chemical ligands to activate the sweet taste receptor highlights the importance of sweet-tasting foods during human evolution...
July 2018: Current Opinion in Clinical Nutrition and Metabolic Care
Jian-Xia Shi, Qin Huang
Glucagon‑like peptide‑1 (GLP‑1) is a gut incretin hormone that is considered to be a promising target for the treatment of patients with type 2 diabetes. However, the mechanisms underlying the protective effects of GLP‑1 on diabetic nephropathy are yet to be fully elucidated. Sirtuin (SIRT)1 encodes a member of the SIRT family of proteins that serves an important role in mitochondrial function and is reported to be associated with the pathogenesis of chronic kidney disease. The present study treated mouse podocytes with various concentrations of D‑glucose to establish a high glucose (HG)‑induced model of renal injury...
May 29, 2018: Molecular Medicine Reports
Uma Anand, Yiangos Yiangou, Ayesha Akbar, Tom Quick, Anthony MacQuillan, Mike Fox, Marco Sinisi, Yuri E Korchev, Ben Jones, Steve R Bloom, Praveen Anand
INTRODUCTION: Glucagon like-peptide 1 receptor (GLP-1R) agonists diminish appetite and may contribute to the weight loss in inflammatory bowel disease (IBD). OBJECTIVES: The aim of this study was to determine, for the first time, the expression of GLP-1R by colon nerve fibres in patients with IBD, and functional effects of its agonists in cultured rat and human sensory neurons. METHODS: GLP-1R and other nerve markers were studied by immunohistochemistry in colon biopsies from patients with IBD (n = 16) and controls (n = 8), human dorsal root ganglia (DRG) tissue, and in GLP-1R transfected HEK293 cells...
2018: PloS One
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