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https://www.readbyqxmd.com/read/28092375/postprandial-macrophage-derived-il-1%C3%AE-stimulates-insulin-and-both-synergistically-promote-glucose-disposal-and-inflammation
#1
Erez Dror, Elise Dalmas, Daniel T Meier, Stephan Wueest, Julien Thévenet, Constanze Thienel, Katharina Timper, Thierry M Nordmann, Shuyang Traub, Friederike Schulze, Flurin Item, David Vallois, Francois Pattou, Julie Kerr-Conte, Vanessa Lavallard, Thierry Berney, Bernard Thorens, Daniel Konrad, Marianne Böni-Schnetzler, Marc Y Donath
The deleterious effect of chronic activation of the IL-1β system on type 2 diabetes and other metabolic diseases is well documented. However, a possible physiological role for IL-1β in glucose metabolism has remained unexplored. Here we found that feeding induced a physiological increase in the number of peritoneal macrophages that secreted IL-1β, in a glucose-dependent manner. Subsequently, IL-1β contributed to the postprandial stimulation of insulin secretion. Accordingly, lack of endogenous IL-1β signaling in mice during refeeding and obesity diminished the concentration of insulin in plasma...
January 16, 2017: Nature Immunology
https://www.readbyqxmd.com/read/28090231/effects-of-ipragliflozin-on-diabetic-nephropathy-and-blood-pressure-in-patients-with-type-2-diabetes-an-open-label-study
#2
Daisuke Ito, Emi Ikuma-Suwa, Kazuyuki Inoue, Kimie Kaneko, Morifumi Yanagisawa, Kouichi Inukai, Mitsuhiko Noda, Akira Shimada
BACKGROUND: Sodium-glucose cotransporter 2 (SGLT2) inhibitors are novel agents used to treat type 2 diabetic patients. We investigated the efficacy of the SGLT2 inhibitor ipragliflozin on diabetic nephropathy in Japanese patients with type 2 diabetes. METHODS: A 50 mg dose of ipragliflozin was administered for 24 weeks to 50 patients with type 2 diabetes who were concomitantly managed with diet and exercise therapy alone or antidiabetic medications other than SGLT2 inhibitors...
February 2017: Journal of Clinical Medicine Research
https://www.readbyqxmd.com/read/28090050/euglycemic-diabetic-ketoacidosis-with-persistent-diuresis-treated-with-canagliflozin
#3
Junichiro Adachi, Yuusuke Inaba, Chisato Maki
Diabetic ketoacidosis is characterized by hyperglycemia, anion-gap acidosis, and increased plasma ketones. After the resolution of hyperglycemia, persistent diuresis is rare. We herein report the case of a 27-year-old Asian woman with type 2 diabetes who was treated with a sodium-glucose cotransporter 2 (SGLT2) inhibitor (canagliflozin) who developed euglycemic diabetic ketoacidosis and persistent diuresis in the absence of hyperglycemia. Physicians should consider euglycemic diabetic ketoacidosis in the differential diagnosis of patients treated with SGLT2 inhibitors...
2017: Internal Medicine
https://www.readbyqxmd.com/read/28086951/sodium-glucose-transporter-2-sglt2-inhibition-with-empagliflozin-improves-cardiac-diastolic-function-in-a-female-rodent-model-of-diabetes
#4
Javad Habibi, Annayya R Aroor, James R Sowers, Guanghong Jia, Melvin R Hayden, Mona Garro, Brady Barron, Eric Mayoux, R Scott Rector, Adam Whaley-Connell, Vincent G DeMarco
Obese and diabetic individuals are at increased risk for impairments in diastolic relaxation and heart failure with preserved ejection fraction. The impairments in diastolic relaxation are especially pronounced in obese and diabetic women and predict future cardiovascular disease (CVD) events in this population. Recent clinical data suggest sodium glucose transporter-2 (SGLT2) inhibition reduces CVD events in diabetic individuals, but the mechanisms of this CVD protection are unknown. To determine whether targeting SGLT2 improves diastolic relaxation, we utilized empagliflozin (EMPA) in female db/db mice...
January 13, 2017: Cardiovascular Diabetology
https://www.readbyqxmd.com/read/28074254/the-cardiovascular-benefits-of-empagliflozin-sglt2-dependent-and-independent-effects
#5
EDITORIAL
Roberto Vettor, Silvio E Inzucchi, Paola Fioretto
No abstract text is available yet for this article.
January 11, 2017: Diabetologia
https://www.readbyqxmd.com/read/28068585/effects-of-phosphate-binders-on-the-gastrointestinal-absorption-of-arsenate-and-of-an-sglt2-inhibitor-drug-on-the-urinary-excretion-of-arsenite-in-mice
#6
Miklós Poór, Balázs Németi, Zoltán Gregus
Arsenate (As(V)) and arsenite (As(III)) are typical sources of acute and chronic arsenic poisoning. Therefore, reducing inner exposure to these arsenicals is a rational objective. Because As(V) mimics phosphate, phosphate binder drugs may decrease the intestinal As(V) absorption. Indeed, lanthanum and aluminium salts and sevelamer removed As(V) from solution in vitro, especially at acidic pH. In mice gavaged with As(V), lanthanum chloride, lanthanum carbonate and aluminium hydroxide given orally also lowered the urinary excretion and tissue levels of As(V) and its metabolites, indicating that they decreased the gastrointestinal As(V) absorption...
January 3, 2017: Environmental Toxicology and Pharmacology
https://www.readbyqxmd.com/read/28063156/effect-of-a-selective-sglt2-inhibitor-luseogliflozin-on-circadian-rhythm-of-sympathetic-nervous-function-and-locomotor-activities-in-metabolic-syndrome-rats
#7
Asadur Rahman, Yoshihide Fujisawa, Daisuke Nakano, Hirofumi Hitomi, Akira Nishiyama
Metabolic syndrome is often associated with disruption of circadian rhythm of systemic hemodynamics and cardiovascular disease. Experiments were conducted to investigate the effects of luseogliflozin, a selective SGLT2 inhibitor, on circadian rhythm of sympathetic nervous function and locomotor activity (LA) in metabolic syndrome rats. The difference in the low frequency component of systolic blood pressure between the dark and light period significantly increased in the luseogliflozin-treated SHRcp. LA also increased in the dark period compared with the light period following luseogliflozin treatment...
January 7, 2017: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/28052965/the-sglt2-inhibitor-dapagliflozin-prevents-cardiomyopathy-in-a-diabetic-lipodystrophic-mouse-model
#8
Michael Joubert, Benoît Jagu, David Montaigne, Xavier Marechal, Angela Tesse, Audrey Ayer, Lucile Dollet, Cédric Le May, Gilles Toumaniantz, Alain Manrique, Flavien Charpentier, Bart Staels, Jocelyne Magré, Bertand Cariou, Xavier Prieur
Type 2 diabetes mellitus (T2DM) is a well-recognized independent risk factor for heart failure (HF). T2DM is associated with altered cardiac energy metabolism, leading to ectopic lipid accumulation and glucose overload, the exact contribution of these two parameters remaining unclear. To provide new insight into the mechanism driving the development of diabetic cardiomyopathy, we studied a unique model of T2DM: lipodystrophic Bscl2(-/-) (seipin knockout (SKO)) mice. Echocardiography and cardiac magnetic resonance imaging revealed hypertrophic cardiomyopathy with left ventricular dysfunction in SKO mice and these two abnormalities were strongly correlated with hyperglycemia...
January 4, 2017: Diabetes
https://www.readbyqxmd.com/read/28043708/emerging-roles-of-sodium-glucose-cotransporter-2-inhibitors-in-cardiology
#9
REVIEW
Atsushi Tanaka, Koichi Node
The ultimate goal of treatment in people with diabetes mellitus is to prevent development of cardiovascular (CV) disease, resulting in prolongation of healthy life expectancy. Although impaired glycemic metabolism has a central role in its pathology, a number of studies have demonstrated that remedy for its imbalance cannot necessarily be accomplished as a therapeutic goal. A comprehensive medical approach against multi-factorial pathologies in diabetes, such as insulin resistance, obesity, hypertension, and dyslipidemia, in addition to diet and exercise therapy should be rather performed in the routine clinical setting...
December 30, 2016: Journal of Cardiology
https://www.readbyqxmd.com/read/28039605/pharmacokinetic-characteristics-and-clinical-efficacy-of-an-sglt2-inhibitor-plus-dpp-4-inhibitor-combination-therapy-in-type-2-diabetes
#10
REVIEW
André J Scheen
Type 2 diabetes (T2D) generally requires a combination of several pharmacological approaches to control hyperglycaemia. Combining a sodium-glucose cotransporter type 2 inhibitor (SGLT2I, also known as gliflozin) and a dipeptidyl peptidase-4 inhibitor (DPP-4I, also known as gliptin) appears to be an attractive strategy because of complementary modes of action. This narrative review analyzes the pharmacokinetics and clinical efficacy of different combined therapies with an SGLT2I (canagliflozin, dapagliflozin, empagliflozin, ertugliflozin, ipragliflozin, luseogliflozin, tofogliflozin) and DPP-4I (linagliptin, saxagliptin, sitagliptin, teneligliptin)...
December 30, 2016: Clinical Pharmacokinetics
https://www.readbyqxmd.com/read/28029152/hypertension-in-2016-blood-pressure-goals-variability-and-sglt2-blockade-in-ckd
#11
Debbie L Cohen, Raymond R Townsend
No abstract text is available yet for this article.
December 28, 2016: Nature Reviews. Nephrology
https://www.readbyqxmd.com/read/28019064/novel-antidiabetic-medications-for-nonalcoholic-fatty-liver-disease-with-type-2-diabetes
#12
REVIEW
Yoshio Sumida, Yuya Seko, Masashi Yoneda
Liver related diseases are the leading causes of death in type 2 diabetes mellitus (T2DM) in Japan. T2DM is closely associated with nonalcoholic fatty liver disease (NAFLD) which is the most prevalent chronic liver disease worldwide. Nonalcoholic steatohepatitis (NASH), a severe form of NAFLD, can lead to hepatocellular carcinoma (HCC) and hepatic failure. NASH can be called "diabetic hepatopathy". There are no established pharmacotherapies for NAFLD/NASH patients with T2DM. Although metformin is established as the first-line therapy for T2DM, given its relative safety and beneficial effects on glycosylated hemoglobin (HbA1c), weight, and cardiovascular mortality, this agent is not recommended as specific therapy for NASH/NAFLD due to no clinical evidences...
December 26, 2016: Hepatology Research: the Official Journal of the Japan Society of Hepatology
https://www.readbyqxmd.com/read/28003053/sglt2-inhibitor-associated-diabetic-ketoacidosis-clinical-review-and-recommendations-for-prevention-and-diagnosis
#13
REVIEW
Ronald M Goldenberg, Lori D Berard, Alice Y Y Cheng, Jeremy D Gilbert, Subodh Verma, Vincent C Woo, Jean-François Yale
PURPOSE: Sodium-glucose cotransporter 2 (SGLT2) inhibitors are the newest class of antihyperglycemic agents available on the market. Regulator warnings and concerns regarding the risk of developing diabetic ketoacidosis (DKA), however, have dampened enthusiasm for the class despite the combined glycemic, blood pressure, and occasional weight benefits of SGLT2 inhibitors. With the goal of improving patient safety, a cross-Canada expert panel and writing group were convened to review the evidence to-date on reported SGLT2 inhibitor-related DKA incidents and to offer recommendations for preventing and recognizing patients with SGLT2 inhibitor-associated DKA...
December 2016: Clinical Therapeutics
https://www.readbyqxmd.com/read/27990776/sglt2-inhibitor-use-and-dietary-carbohydrate-intake-in-japanese-individuals-with-type-2-diabetes-a-randomized-open-label-3-arm-parallel-comparative-exploratory-study
#14
Daisuke Yabe, Masahiro Iwasaki, Hitoshi Kuwata, Takuya Haraguchi, Yoshiyuki Hamamoto, Takeshi Kurose, Kiminobu Sumita, Hitoshi Yamazato, Shigeto Kanada, Yutaka Seino
This study investigated safety and efficacy of the SGLT2 inhibitor luseogliflozin under differing carbohydrate intake in Japanese individuals with type 2 diabetes (T2D). Subjects were randomly assigned to three carbohydrate-adjusted meals for 14 days (Days 1-14) [HC-HGI, 55% total energy carbohydrate (TEC) and high glycemic index (GI); HC-LGI, 55% TEC and low GI; and LC-HGI, 40% TEC and high GI]. All subjects received luseogliflozin for the last 7 days (Days 8-14); continuous glucose monitoring (CGM) before and after luseogliflozin treatment (Days 5-8 and Days 12-15); and blood tests on Days 1, 8, and 15...
December 19, 2016: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/27989651/the-impact-of-sglt2-inhibitors-compared-with-insulin-on-diabetic-bone-disease-in-a-mouse-model-of-type-1-diabetes
#15
Kathryn M Thrailkill, Jeffry S Nyman, R Clay Bunn, Sasidhar Uppuganti, Katherine L Thompson, Charles K Lumpkin, Evangelia Kalaitzoglou, John L Fowlkes
Skeletal co-morbidities in type 1 diabetes include an increased risk for fracture and delayed fracture healing, which are intertwined with disease duration and the presence of other diabetic complications. As such, chronic hyperglycemia is undoubtedly a major contributor to these outcomes, despite standard insulin-replacement therapy. Therefore, using the streptozotocin (STZ)-induced model of hypoinsulinemic hyperglycemia in DBA/2J male mice, we compared the effects of two glucose lowering therapies on the fracture resistance of bone and markers of bone turnover...
October 28, 2016: Bone
https://www.readbyqxmd.com/read/27981497/factors-affecting-canagliflozin-induced-transient-urine-volume-increase-in-patients-with-type-2-diabetes-mellitus
#16
Hiroyuki Tanaka, Kazuhiko Takano, Hiroaki Iijima, Hajime Kubo, Nobuko Maruyama, Toshio Hashimoto, Kenji Arakawa, Masanori Togo, Nobuya Inagaki, Kohei Kaku
INTRODUCTION: Sodium glucose co-transporter 2 (SGLT2) inhibitors exhibit diuretic activity, which is a possible mechanism underlying the cardiovascular benefit of these inhibitors. However, the osmotic diuresis-induced increase in urine volume, and the risk of dehydration have been of concern with SGLT2 inhibitor treatment. This study aimed to investigate the mechanism underlying SGLT2 inhibitor canagliflozin-induced diuresis in Japanese type 2 diabetes mellitus (T2DM) patients. METHODS: Thirteen T2DM patients received a daily oral dose of 100 mg canagliflozin before breakfast for 6 days...
December 15, 2016: Advances in Therapy
https://www.readbyqxmd.com/read/27977934/longer-term-safety-and-tolerability-of-canagliflozin-in-patients-with-type-2-diabetes-a-pooled-analysis
#17
Rong Qiu, Dainius Balis, John Xie, Michael J Davies, Mehul Desai, Gary Meininger
OBJECTIVE: To evaluate the longer-term safety of canagliflozin, an SGLT2 inhibitor, in patients with type 2 diabetes mellitus (T2DM). METHODS: The safety/tolerability of canagliflozin 100 and 300mg were assessed using data pooled from 7 placebo- and active-controlled studies of 52-104 weeks in duration that enrolled a broad range of patients with T2DM (N = 5598). Canagliflozin 100 and 300mg as monotherapy or in combination with various background antihyperglycemic agents (AHAs) were compared with pooled non-canagliflozin treatments (ie, placebo, sitagliptin, glimepiride)...
December 15, 2016: Current Medical Research and Opinion
https://www.readbyqxmd.com/read/27972174/the-cost-of-glycaemic-target-achievement-with-sodium-glucose-co-transporter-2-sglt2-inhibitors-in-patients-with-type-2-diabetes-mellitus-t2dm-inadequately-controlled-on-metformin-and-sulphonylurea-met-su-in-the-uk
#18
M Evans, M Schroeder, A Schubert, C Neslusan
No abstract text is available yet for this article.
November 2016: Value in Health: the Journal of the International Society for Pharmacoeconomics and Outcomes Research
https://www.readbyqxmd.com/read/27941935/renal-metabolic-and-cardiovascular-considerations-of-sglt2-inhibition
#19
REVIEW
Ralph A DeFronzo, Luke Norton, Muhammad Abdul-Ghani
The kidney has a pivotal role in maintaining glucose homeostasis by using glucose as a metabolic fuel, by producing glucose through gluconeogenesis, and by reabsorbing all filtered glucose through the sodium-glucose cotransporters SGLT1 and SGLT2 located in the proximal tubule. In patients with diabetes, the maximum glucose reabsorptive capacity (TmG) of the kidney, as well as the threshold for glucose spillage into the urine, are elevated, contributing to the pathogenesis of hyperglycaemia. By reducing the TmG and, more importantly, the threshold of glucosuria, SGLT2 inhibitors enhance glucose excretion, leading to a reduction in fasting and postprandial plasma glucose levels and improvements in both insulin secretion and insulin sensitivity...
January 2017: Nature Reviews. Nephrology
https://www.readbyqxmd.com/read/27933185/circulating-serpinb1-levels-and-clinical-features-in-patients-with-type-2-diabetes
#20
Kohzo Takebayashi, Kenji Hara, Tomoko Terasawa, Rika Naruse, Mariko Suetsugu, Takafumi Tsuchiya, Toshihiko Inukai
OBJECTIVE: The main purpose of this study was to investigate the association of serum SerpinB1 levels and various parameters in patients with type 2 diabetes. The effect of canagliflozin (a sodium glucose cotransporter 2 (SGLT2) inhibitor), which can decrease circulating insulin levels, on serum SerpinB1 levels was also investigated. A recent study suggests that the serum levels of SerpinB1, also known as monocyte neutrophil elastase inhibitor, increase with insulin resistance, may have a protective effect for pancreatic β cells, and may decrease insulin resistance...
2016: BMJ Open Diabetes Research & Care
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