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https://www.readbyqxmd.com/read/28109166/a-novel-dual-amylin-and-calcitonin-receptor-agonist-dacra-kbp-089-induces-weight-loss-through-a-reduction-in-fat-but-not-lean-mass-while-improving-food-preference
#1
Sofie Gydesen, Sara Toftegaard Hjuler, Zenia Freving, Kim Vietz Andreassen, Nina Sonne, Lars I Hellgren, Morten Asser Karsdal, Kim Henriksen
BACKGROUND AND PURPOSE: Obesity and associated co-morbidities, such as type 2 diabetes and non-alcoholic fatty liver disease, are major health challenges - hence, development of weight loss therapies with the ability to reduce the co-morbidities is key. EXPERIMENTAL APPROACH: The effect of the dual amylin and calcitonin receptor agonist (DACRA), KBP-089, on bodyweight, glucose homeostasis, and fatty acid accumulation in liver and muscle tissue, food preference was investigated...
January 21, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28104753/the-effect-of-adrenal-medullectomy-on-metabolic-responses-to-chronic-intermittent-hypoxia-in-the-frequently-sampled-intravenous-glucose-tolerance-test
#2
Mi-Kyung Shin, Woobum Han, Hoon Joo, Shannon Bevans-Fonti, Masakazu Shiota, Darko Stefanovski, Vsevolod Y Polotsky
Obstructive sleep apnea is associated with type 2 diabetes. We have previously developed a mouse model of intermittent hypoxia (IH) mimicking oxyhemoglobin desaturations in patients with sleep apnea and have shown that IH increases fasting glucose, hepatic glucose output, and plasma catecholamines. We hypothesize that adrenal medulla modulates glucose responses to IH, and that such responses can be prevented by adrenal medullectomy. We performed adrenal medullectomy or sham surgery in lean C57BL/6J mice, which were exposed to IH or intermittent air (control) for 4 weeks followed by the frequently sampled intravenous glucose tolerance test (FSIVGTT) in unanesthetized unrestrained animals...
January 19, 2017: Journal of Applied Physiology
https://www.readbyqxmd.com/read/28097011/a-selective-gpr40-ffar1-agonist-ly2881835-provides-immediate-and-durable-glucose-control-in-rodent-models-of-type-2-diabetes
#3
Yanyun Chen, Min Song, Jonathan P Riley, Charlie C Hu, Xianbu Peng, Donalyn Scheuner, Krister Bokvist, Pranab Maiti, Steven D Kahl, Chahrzad Montrose-Rafizadeh, Chafiq Hamdouchi, Anne Reifel Miller
LY2881835 is a selective, potent, and efficacious GPR40 agonist. The objective of the studies described here was to examine the pharmacological properties of LY2881835 in preclinical models of T2D. Significant increases in insulin secretion were detected when LY2881835 was tested in primary islets from WT mice but not in islets from GPR40 KO mice. Furthermore, LY2881835 potentiated glucose stimulated insulin secretion in normal lean mice. Acute administration of LY2881835 lowered glucose during OGTTs in WT mice but not in GPR40 KO mice...
December 2016: Pharmacology Research & Perspectives
https://www.readbyqxmd.com/read/28096259/bariatric-surgery-enhances-splanchnic-vascular-responses-in-patients-with-type-2-diabetes
#4
Henri Honka, Jukka Koffert, Saila Kauhanen, Jarmo Teuho, Saija Hurme, Andrea Mari, Andreas Lindqvist, Nils Wierup, Leif Groop, Pirjo Nuutila
Bariatric surgery results in notable weight loss and alleviates hyperglycemia in patients with type 2 diabetes (T2D). In this study, we aimed to characterize the vascular effects of a mixed-meal and of infusion of exogenous glucose-dependent insulinotropic polypeptide (GIP) in the splanchnic region in ten obese patients with T2D before and after bariatric surgery and in ten lean controls. The experiments were carried out on two separate days. Pancreatic and intestinal blood flow (BF) were measured at baseline, 20 and 50 minutes with (15)O-water using positron emission tomography and magnetic resonance imaging (PET/MRI)...
January 17, 2017: Diabetes
https://www.readbyqxmd.com/read/28095372/impaired-mitochondrial-respiration-in-large-cerebral-arteries-of-rats-with-type-2-diabetes
#5
Ivan Merdzo, Ibolya Rutkai, Venkata N L R Sure, Catherine A McNulty, Prasad V G Katakam, David W Busija
Mitochondrial dysfunction has been suggested as a potential underlying cause of pathological conditions associated with type 2 diabetes (T2DM). We have previously shown that mitochondrial respiration and mitochondrial protein levels were similar in the large cerebral arteries of insulin-resistant Zucker obese rats and their lean controls. In this study, we extend our investigations into the mitochondrial dynamics of the cerebral vasculature of 14-week-old Zucker diabetic fatty obese (ZDFO) rats with early T2DM...
January 18, 2017: Journal of Vascular Research
https://www.readbyqxmd.com/read/28093849/obesity-and-type-2-diabetes-are-associated-with-elevated-pcsk9-levels-in-young-women
#6
Amy E Levenson, Amy S Shah, Philip R Khoury, Thomas R Kimball, Elaine M Urbina, Sarah D de Ferranti, David M Maahs, Lawrence M Dolan, R Paul Wadwa, Sudha B Biddinger
BACKGROUND: Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a key regulator of low-density lipoprotein cholesterol and cardiovascular disease risk, and is an emerging therapeutic target. OBJECTIVE: We compared serum PCSK9 levels in young adults, with and without type 2 diabetes. SUBJECTS AND METHODS: Cross-sectional analysis was conducted in a cohort, aged 15 to 26 years, in Cincinnati, OH, from 2005 to 2010. Serum PCSK9 levels were measured in 94 youth with type 2 diabetes, 93 obese control subjects, and 99 lean control subjects...
January 17, 2017: Pediatric Diabetes
https://www.readbyqxmd.com/read/28092457/insulin-sensitivity-and-inflammation-mediate-the-impact-of-fitness-on-cerebrovascular-health-in-adolescents
#7
Po Lai Yau, Naima Ross, Andrew Tirsi, Arslan Arif, Zeynep Ozinci, Antonio Convit
BACKGROUND/OBJECTIVES: To investigate in adolescents the relationships between retinal vessel diameter, physical fitness, insulin sensitivity, and systemic inflammation. METHODS: We evaluated 157 adolescents, 112 with excessive weight and 45 lean, all without type 2 diabetes mellitus. All received detailed evaluations, including measurements of retinal vessel diameter, insulin sensitivity, levels of inflammation, and physical fitness. RESULTS: Overweight/obese adolescents had significantly narrower retinal arteriolar and wider venular diameters, significantly lower insulin sensitivity, and physical fitness...
January 16, 2017: Childhood Obesity
https://www.readbyqxmd.com/read/28073779/glucose-dependent-insulinotropic-polypeptide-promotes-lipid-deposition-in-subcutaneous-adipocytes-in-obese-type-2-diabetes-patients-a-maladaptive-response
#8
Sravan K Thondam, Christina Daousi, John P H Wilding, Jens J Holst, Gulizar I Ameen, Chenjing Yang, Catherine Whitmore, Silvia Mora, Daniel J Cuthbertson
: Glucose-dependent insulinotropic polypeptide (GIP) beyond its insulinotropic effects may regulate post-prandial lipid metabolism. While the insulinotropic action of GIP is known to be impaired in type 2 diabetes mellitus (T2DM), its adipogenic effect is unknown. We hypothesised GIP is anabolic in human subcutaneous adipose tissue (SAT) promoting triacylglycerol (TAG) deposition through re-esterification of non-esterified fatty acids (NEFA) and this effect may differ according to obesity status or glucose tolerance...
January 10, 2017: American Journal of Physiology. Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28067023/elevated-serum-milk-fat-globule-epidermal-growth-factor-8-levels-in-type-2-diabetic-patients-are-suppressed-by-overweight-or-obese-status
#9
Yuanyuan Li, Wenzhuo Ran, Jiaqiang Zhang, Shi Chen, Yihang Li, Deng Luo, Chen Wang, Weiping Jia
Inflammation is the most important link between obesity and type 2 diabetes (T2D). Although milk fat globule-epidermal growth factor 8 (MFG-E8) is a key mediator in anti-inflammatory responses, its role in obesity and diabetes is not yet completely understood. We aimed to measure MFG-E8 serum levels and to explore the role of MFG-E8 in obesity and T2D. Fasting serum MFG-E8 levels were quantified by enzyme-linked immunosorbent assay for 168 individuals, whose oral glucose tolerance test was conducted, and levels of inflammatory factors, including tumor necrosis factor-α (TNF-α) and C-reactive protein, were measured...
January 9, 2017: IUBMB Life
https://www.readbyqxmd.com/read/28065772/multimorbidity-in-middle-aged-adults-with-cerebral-palsy
#10
Nicole Cremer, Edward A Hurvitz, Mark D Peterson
BACKGROUND: Individuals with cerebral palsy have less lean body mass, greater relative adiposity, and lower fitness and physical activity participation; and yet, the prevalence of age-related multimorbidity in this population has yet to be established. PURPOSE: To examine the prevalence of lifestyle-related chronic conditions and multimorbidity in a sample of middle-aged adults with cerebral palsy. METHODS: A clinic-based sample of middle-aged adults with cerebral palsy was examined using Electronic Medical Records Search Engine (EMERSE) software...
January 5, 2017: American Journal of Medicine
https://www.readbyqxmd.com/read/28061846/map4k4-and-il-6-th17-cells-play-important-roles-in-non-obese-type-2-diabetes
#11
REVIEW
Huai-Chia Chuang, Tse-Hua Tan
Obesity is a causal factor of type 2 diabetes (T2D); however, people without obesity (including lean, normal weight, or overweight) may still develop T2D. Non-obese T2D is prevalent in Asia and also frequently occurs in Europe. Recently, multiple evidences oppose the notion that either obesity or central obesity (visceral fat accumulation) promotes non-obese T2D. Several factors such as inflammation and environmental factors contribute to non-obese T2D. According to the data derived from gene knockout mice and T2D clinical samples in Asia and Europe, the pathogenesis of non-obese T2D has been unveiled recently...
January 7, 2017: Journal of Biomedical Science
https://www.readbyqxmd.com/read/28061324/oral-corticosterone-administration-reduces-insulitis-but-promotes-insulin-resistance-and-hyperglycemia-in-male-nonobese-diabetic-mice
#12
Susan J Burke, Heidi M Batdorf, Adrianna E Eder, Michael D Karlstad, David H Burk, Robert C Noland, Z Elizabeth Floyd, J Jason Collier
Steroid-induced diabetes is the most common form of drug-induced hyperglycemia. Therefore, metabolic and immunological alterations associated with chronic oral corticosterone were investigated using male nonobese diabetic mice. Three weeks after corticosterone delivery, there was reduced sensitivity to insulin action measured by insulin tolerance test. Body composition measurements revealed increased fat mass and decreased lean mass. Overt hyperglycemia (>250 mg/dL) manifested 6 weeks after the start of glucocorticoid administration, whereas 100% of the mice receiving the vehicle control remained normoglycemic...
January 4, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28052966/role-of-adipose-tissue-insulin-resistance-in-the-natural-history-of-t2dm-results-from-the-san-antonio-metabolism-study
#13
Amalia Gastaldelli, Melania Gaggini, Ralph A DeFronzo
In the transition from normal glucose tolerance (NGT) to type 2 diabetes mellitus (T2DM), the role of β-cell dysfunction and peripheral insulin resistance (IR) is well established. However, the impact of dysfunctional adipose tissue has not been fully elucidated. The aim of the present study is to evaluate the role of resistance to the antilipolytic effect of insulin (Adipo-IR) in a large group of NGT, IGT and T2DM subjects.302 subjects with varying glucose tolerance received OGTT and euglycemic insulin clamp...
January 4, 2017: Diabetes
https://www.readbyqxmd.com/read/28035343/effects-of-different-degrees-of-insulin-resistance-on-endothelial-function-in%C3%A2-obese%C3%A2-adults-undergoing-alternate-day%C3%A2-fasting
#14
Kristin K Hoddy, Surabhi Bhutani, Shane A Phillips, Krista A Varady
BACKGROUND: Obesity can have deleterious effects on insulin sensitivity leading to endothelial dysfunction. Whether alternate day fasting (ADF) can ameliorate insulin sensitivity in a way that improves endothelial function remains unknown. OBJECTIVE: This study examined the impact of ADF on endothelium dependent flow mediated dilation (FMD) in obese subjects with different degrees of insulin resistance. METHODS: Obese non-diabetic adults (n = 54) participated in an 8-week ADF protocol (25% energy intake "fast day", alternated with ad libitum intake "feast day")...
October 27, 2016: Nutr Healthy Aging
https://www.readbyqxmd.com/read/28027925/impact-of-prebiotics-on-metabolic-and-behavioral-alterations-in-a-mouse-model-of-metabolic-syndrome
#15
Lourdes Fernández de Cossío, Célia Fourrier, Julie Sauvant, Amandine Everard, Lucile Capuron, Patrice D Cani, Sophie Layé, Nathalie Castanon
Mounting evidence shows that the gut microbiota, an important player within the gut-brain communication axis, can affect metabolism, inflammation, brain function and behavior. Interestingly, gut microbiota composition is known to be altered in patients with metabolic syndrome (MetS), who also often display neuropsychiatric symptoms. The use of prebiotics, which beneficially alters the microbiota, may therefore be a promising way to potentially improve physical and mental health in MetS patients. This hypothesis was tested in a mouse model of MetS, namely the obese and type-2 diabetic db/db mice, which display emotional and cognitive alterations associated with changes in gut microbiota composition and hippocampal inflammation compared to their lean db/+ littermates...
December 24, 2016: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/28024987/effects-of-high-intensity-training-on-cardiovascular-risk-factors-in-premenopausal-and-postmenopausal-women
#16
Camilla M Mandrup, Jon Egelund, Michael Nyberg, Martina H Lundberg Slingsby, Caroline Andersen, Sofie Løgstrup, Jens Bangsbo, Charlotte Suetta, Bente Stallknecht, Ylva Hellsten
BACKGROUND: Menopause is associated with increased risk of cardiovascular disease and the causal factors have been proposed to be the loss of estrogen and the subsequent alterations of the hormonal milieu. However, which factors contribute to the deterioration of cardiometabolic health in postmenopausal women is debated as the menopausal transition is also associated with increased age and fat mass. Furthermore, indications of reduced cardiometabolic adaptations to exercise in postmenopausal women add to the adverse health profile...
December 23, 2016: American Journal of Obstetrics and Gynecology
https://www.readbyqxmd.com/read/28024880/embryonic-ablation-of-neuronal-vgf-increases-energy-expenditure-and-reduces-body-weight
#17
Cheng Jiang, Wei-Jye Lin, Masato Sadahiro, Andrew C Shin, Christoph Buettner, Stephen R Salton
Germline ablation of VGF, a secreted neuronal, neuroendocrine, and endocrine peptide precursor, results in lean, hypermetabolic, and infertile adult mice that are resistant to diet-, lesion-, and genetically-induced obesity and diabetes (Hahm et al., 1999, 2002). To assess whether this phenotype is predominantly driven by reduced VGF expression in developing and/or adult neurons, or in peripheral endocrine and neuroendocrine tissues, we generated and analyzed conditional VGF knockout mice, obtained by mating loxP-flanked (floxed) Vgf mice with either pan-neuronal Synapsin-Cre- or forebrain alpha-CaMKII-Cre-recombinase-expressing transgenic mice...
December 20, 2016: Neuropeptides
https://www.readbyqxmd.com/read/28018292/obesity-an-immunometabolic-perspective
#18
REVIEW
Indrani Ray, Sushil K Mahata, Rajat K De
Obesity, characterized by chronic activation of inflammatory pathways, is a critical factor contributing to insulin resistance (IR) and type 2 diabetes (T2D). Free fatty acids (FFAs) are increased in obesity and are implicated as proximate causes of IR and induction of inflammatory signaling in adipose, liver, muscle, and pancreas. Cells of the innate immune system produce cytokines, and other factors that affect insulin signaling and result in the development of IR. In the lean state, adipose tissue is populated by adipose tissue macrophage of the anti-inflammatory M2 type (ATM2) and natural killer (NK) cells; this maintains the insulin-sensitive phenotype because ATM2 cells secrete IL10...
2016: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/28017449/anabolic-resistance-does-not-explain-sarcopenia-in-patients-with-type-2-diabetes-mellitus-compared-with-healthy-controls-despite-reduced-mtor-pathway-activity
#19
Daniel J Cuthbertson, John Babraj, Graham Leese, Mario Siervo
BACKGROUND: Ageing and type 2 diabetes mellitus (T2DM) are risk factors for skeletal muscle loss. We investigated whether anabolic resistance to feeding might underlie accelerated muscle loss in older people with T2DM and whether dysregulated mTOR signalling was implicated. SUBJECTS: 8 obese men with T2DM, and 12 age-matched controls were studied (age 68 ± 3 vs. 68±6 y; BMI: 30 ± 2 vs. 27 ± 5 kg m(-2)). METHODS: Body composition was measured by dual-X-ray absorptiometry...
November 25, 2016: Clinical Nutrition: Official Journal of the European Society of Parenteral and Enteral Nutrition
https://www.readbyqxmd.com/read/28007534/fkbp5-polymorphism-is-associated-with-insulin-resistance-in-children-and-adolescents-with-obesity
#20
Marta Fichna, Izabela Krzyśko-Pieczka, Magdalena Żurawek, Bogda Skowrońska, Danuta Januszkiewicz-Lewandowska, Piotr Fichna
OBJECTIVE: Since metabolic syndrome shares several clinical features with hypercortisolism, it was hypothesised that genes altering individual glucocorticoid (GC) sensitivity might be implicated in pathogenesis of obesity and its adverse outcomes. FKBP5 gene encodes a chaperon protein in the GC receptor (GR) complex, which modulates steroid action upon target genes. Its functional variant, rs1360780, may enhance FKBP5 gene transcription, affect GR signalling and thereby influence the hypothalamo-pituitary-adrenal axis...
December 19, 2016: Obesity Research & Clinical Practice
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