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https://www.readbyqxmd.com/read/28431667/the-potential-and-pitfalls-of-glp-1-receptor-agonists-for-renal-protection-in-type-2-diabetes
#1
Merlin C Thomas
Glucagon-Like Peptide-1 Receptor agonists (GLP-1 RA) offer substantial benefits for the management of glucose levels in type 2 diabetes. In addition, recent data from clinical trials have demonstrated that treatment with Glucagon-Like Peptide-1 Receptor agonists (GLP-1 RA) are also able to reduce new onset macroalbuminuria. These benefits may be consistent with the known effects of GLP-1 RA on traditional risk factors for progressive kidney disease including glucose lowering, blood pressure lowering, reduced insulin levels and weight reduction...
April 2017: Diabetes & Metabolism
https://www.readbyqxmd.com/read/28428225/empagliflozin-and-kinetics-of-renal-glucose-transport-in-healthy-and-type-2-diabetic-individuals
#2
Hussein Al-Jobori, Giuseppe Daniele, Eugenio Cersosimo, Curtis Triplitt, Luke Norton, Ralph A DeFronzo, Muhammad Abdul-Ghani
Renal glucose reabsorption was measured with the stepped-hyperglycemic clamp in 15 T2DM and 15 non-diabetic subjects after 2 days and after more chronic (14 days) treatment with empagliflozin. T2DM patients had significantly greater maximal renal glucose transport (TmG) compared to nondiabetic subjects at baseline (459±53 vs 337±25 mg/min, p<0.05). Empagliflozin treatment for 48 hours reduced the TmG in both diabetic and non-diabetic individuals by 44±7% and 53±6%, respectively (both p<0.001). TmG was further reduced by empagliflozin in both groups on day 14 (by 65±5% and 75±3%, respectively)...
April 20, 2017: Diabetes
https://www.readbyqxmd.com/read/28395380/streptozotocin-treated-high-fat-fed-mice-a-new-type-2-diabetes-model-used-to-study-canagliflozin-induced-alterations-in-lipids-and-lipoproteins
#3
Tian Yu, Mitchell J Sungelo, Ira J Goldberg, Hong Wang, Robert H Eckel
The pharmacological effects of type 2 diabetes (T2DM) medications on lipoprotein metabolism are difficult to assess in preclinical models because those created failure to replicate the human condition in which insulin deficiency is superimposed on obesity-related insulin resistance. To create a better model, we fed mice with high fat (HF) diet and treated the animals with low dose streptozotocin (STZ) to mimic T2DM. We used this model to evaluate the effects of canagliflozin (CANA), a drug that reduces plasma glucose by inhibiting the sodium-glucose transporter 2 (SGLT2), which mediates ~90% of renal glucose reabsorption] on lipid and lipoprotein metabolism...
April 10, 2017: Hormone and Metabolic Research, Hormon- und Stoffwechselforschung, Hormones et Métabolisme
https://www.readbyqxmd.com/read/28395363/natural-products-as-lead-compounds-for-sodium-glucose-cotransporter-sglt-inhibitors
#4
Wolfgang Blaschek
Glucose homeostasis is maintained by antagonistic hormones such as insulin and glucagon as well as by regulation of glucose absorption, gluconeogenesis, biosynthesis and mobilization of glycogen, glucose consumption in all tissues and glomerular filtration, and reabsorption of glucose in the kidneys. Glucose enters or leaves cells mainly with the help of two membrane integrated transporters belonging either to the family of facilitative glucose transporters (GLUTs) or to the family of sodium glucose cotransporters (SGLTs)...
April 10, 2017: Planta Medica
https://www.readbyqxmd.com/read/28393583/spotlight-on-canagliflozin-300-review-of-its-efficacy-and-an-indirect-comparison-to-other-sglt-2-inhibitors-and-long-acting-glp-1-receptor-agonists
#5
Awadhesh Kumar Singh, Ritu Singh
Both sodium-glucose co-transporter-2 inhibitors (SGLT-2Is) and glucagon-like peptide-1 receptor agonists (GLP-1RAs) have been consistently found to lower blood glucose, body weight and systolic blood pressure (SBP) in patients with type 2 diabetes mellitus (T2DM). While all the SGLT-2Is inhibit glucose reabsorption by blocking SGLT-2 receptor in kidney, dose-dependently, the highest licensed dose of canagliflozin 300-mg has an additional ability to inhibit SGLT-1 receptor in intestine transiently, that may lead to additional inhibition of prandial glucose absorption, unlike other approved highly selective SGLT-2Is...
April 17, 2017: Expert Review of Clinical Pharmacology
https://www.readbyqxmd.com/read/28357781/utility-of-baseline-serum-phosphorus-levels-for-predicting-remission-in-acromegaly-patients
#6
G Y Yalin, S Tanrikulu, N Gul, A K Uzum, F Aral, R Tanakol
PURPOSE: High GH and IGF I levels increase tubular phosphate reabsorption in patients with acromegaly. We aimed to investigate the utility of serum phosphorus levels as an indicator for predicting chance of remission in acromegaly patients. DESIGN: Fifty-one patients (n: 51; F: 24, M: 27) with diagnosis of acromegaly were included in the study. Plasma IGF-1, Phosphorus (P) and nadir GH levels on oral glucose tolerance test (OGTT) at the time of diagnosis were analysed retrospectively...
March 29, 2017: Journal of Endocrinological Investigation
https://www.readbyqxmd.com/read/28356283/saving-the-sweetness-renal-glucose-handling-in-health-and-disease
#7
Blythe D Shepard, Jennifer L Pluznick
Glucose homeostasis is highly controlled, and the function of the kidney plays an integral role in this process. The exquisite control of blood glucose relies, in part, on renal glucose filtration, renal glucose reabsorption and renal gluconeogenesis. Particularly critical to maintaining glucose homeostasis is the renal reabsorption of glucose; with ~162g of glucose filtered by the kidney per day, it is imperative that the kidney have the ability to efficiently reabsorb nearly 100% of this glucose back into the bloodstream...
March 29, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28325783/renal-handling-of-ketones-in-response-to-sodium-glucose-cotransporter-2-inhibition-in-patients-with-type-2-diabetes
#8
Ele Ferrannini, Simona Baldi, Silvia Frascerra, Brenno Astiarraga, Elisabetta Barsotti, Aldo Clerico, Elza Muscelli
OBJECTIVE: Pharmacologically induced glycosuria elicits adaptive responses in glucose homeostasis and hormone release, including decrements in plasma glucose and insulin levels, increments in glucagon release, enhanced lipolysis, and stimulation of ketogenesis, resulting in an increase in ketonemia. We aimed at assessing the renal response to these changes. RESEARCH DESIGN AND METHODS: We measured fasting and postmeal urinary excretion of glucose, β-hydroxybutyrate (β-HB), lactate, and sodium in 66 previously reported patients with type 2 diabetes and preserved renal function (estimated glomerular filtration rate ≥60 mL · min(-1) · 1...
March 21, 2017: Diabetes Care
https://www.readbyqxmd.com/read/28299616/promise-of-sglt2-inhibitors-in-heart-failure-diabetes-and-beyond
#9
REVIEW
Pieter Martens, Chantal Mathieu, Frederik H Verbrugge
This review provides mechanistic insight in the pleiotropic effects of sodium-glucose transporter-2 (SGLT-2) inhibitors with particular interest to the pathophysiology of heart failure. The SGLT-2 inhibitor empagliflozin has recently demonstrated an unprecedented 38% reduction in cardiovascular mortality in patients with diabetes. Despite modest effects on long-term glycemic control, highly significant reductions in heart failure admissions and end-stage kidney disease were observed. SGLT-2 inhibitors are the latest approved class of glucose-lowering agents...
March 2017: Current Treatment Options in Cardiovascular Medicine
https://www.readbyqxmd.com/read/28270062/antidiabetic-drugs-and-the-kidney
#10
Moses Elisaf, Eleftheria Tzavela, Nikolaos Karanatsis, Vasilis Tsimichodimos
OBJECTIVE: Nephropathy is among the most common and most devastating complications of diabetes mellitus. Recent data suggest that there is a multifaceted interaction between the kidney and antidiabetic drugs. Thus, the deterioration of renal function may result in important changes in the pharmacokinetic and pharmacodynamic properties of glucose-lowering compounds. Additionally, drugs that exert their antidiabetic properties through the inhibition of proximal glucose reabsorption are now available whereas accumulating evidence suggests that some of these drugs may exert renoprotective properties that are independent of their effect on carbohydrate metabolism...
March 6, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28258533/current-therapeutic-approaches-in-the-management-of-hyperglycemia-in-chronic-renal-disease
#11
REVIEW
Vishnu Garla, Licy Yanes-Cardozo, Lillian F Lien
Diabetes mellitus (DM) and chronic kidney disease (CKD) are intricately intertwined. DM is the most common cause of CKD. Adequate control of DM is necessary for prevention of progression of CKD, while careful management of the metabolic abnormalities in CKD will assist in achieving better control of DM. Two of the key organs involved in glucose production are the kidney and the liver. Furthermore, the kidney also plays a role in glucose filtration and reabsorption. In CKD, monitoring of glycemic control using traditional methods such as Hemoglobin A1c (Hba1c) must be done with caution secondary to associated hematological abnormalities in CKD...
March 3, 2017: Reviews in Endocrine & Metabolic Disorders
https://www.readbyqxmd.com/read/28255241/an-evidence-based-practice-oriented-review-focusing-on-canagliflozin-in-the-management-of-type-2-diabetes
#12
REVIEW
Joseph A Messana, Stanley S Schwartz, Raymond R Townsend
Caring for patients with type 2 diabetes mellitus (T2DM) has entered an era with many recent additions to the regimens used to clinically control their hyperglycemia. The most recent class of agents approved by the Food and Drug Administration (FDA) for T2DM is the sodium-glucose-linked transporter type 2 (SGLT2) inhibitors, which work principally in the proximal tubule of the kidney to block filtered glucose reabsorption. In the few years attending this new class arrival in the market, there has been a great deal of interest generated by the novel mechanism of action of SGLT2 inhibitors and by recent large outcome trials suggesting benefit on important clinical outcomes such as death, cardiovascular disease and kidney disease progression...
2017: Vascular Health and Risk Management
https://www.readbyqxmd.com/read/28245785/vascular-consequences-of-aldosterone-excess-and-mineralocorticoid-receptor-antagonism
#13
Sophocles Chrissobolis
Aldosterone binds to mineralocorticoid receptors (MRs) on renal epithelial cells to regulate sodium and water reabsorption, and therefore blood pressure. Recently, the actions of aldosterone outside the kidney have been extensively investigated, with numerous reports of aldosterone having detrimental actions, including in the vasculature. Notably, elevated aldosterone levels are an independent cardiovascular risk factor, and in addition to causing an increase in blood pressure, aldosterone can have blood pressure-dependent and -independent effects commonly manifested in the vasculature in cardiovascular diseases, including vascular oxidative stress, endothelial dysfunction, inflammation, remodeling, stiffening, and plaque formation...
February 28, 2017: Current Hypertension Reviews
https://www.readbyqxmd.com/read/28244693/dapagliflozin-improves-insulin-resistance-and-glucose-intolerance-in-a-novel-transgenic-rat-with-chronic-glucose-overproduction-and-glucose-toxicity
#14
Christos N Joannides, Salvatore P Mangiafico, Matthew F Waters, Benjamin J Lamont, Sofianos Andrikopoulos
AIMS: Insulin resistance and impaired insulin secretion are cardinal defects that contribute to hyperglycemia in type 2 diabetes. Recently, a new class of drugs called sodium-glucose linked transporter 2 (SGLT2) inhibitors has been introduced that reduce blood glucose by inhibiting glucose reabsorption in the kidney and is not dependent on glucose metabolism or insulin action. The purpose of the present study was to determine whether the excretion of glucose would improve insulin resistance, impaired insulin secretion or both...
February 28, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28243920/involvement-of-glucagon-like-peptide-1-in-the-regulation-of-selective-excretion-of-sodium-or-chloride-ions-by-the-kidneys
#15
A S Marina, A V Kutina, E I Shakhmatoba, Yu V Natochin
An increase of total glucagon-like peptide-1 (GLP-1) concentration in the plasma in rats was revealed 5 min after oral, but not intraperitoneal administration of NaCl or Trizma HCl solutions. The increase in GLP-1 level was similar to that after oral glucose administration. After intraperitoneal administration of 2.5% NaCl, GLP-1 mimetic exenatide accelerated natriuresis and urinary chloride excretion. Under conditions of normonatriemia and hyperchloremia induced by injection of 6.7% Trizma HCl, exenatide stimulated chloride excretion and reabsorption of sodium ions in the kidneys...
February 2017: Bulletin of Experimental Biology and Medicine
https://www.readbyqxmd.com/read/28217522/a-review-of-clinical-efficacy-and-safety-of-canagliflozin-300-mg-in-the-management-of-patients-with-type-2-diabetes-mellitus
#16
REVIEW
K M Prasanna Kumar, Sujoy Ghosh, William Canovatchel, Nishant Garodia, Sujith Rajashekar
Currently available antihyperglycemic agents, despite being effective, provide inadequate glycemic control and/or are associated with side effects or nonadherence. Canagliflozin, a widely used orally active inhibitor of sodium-glucose cotransporter 2 (SGLT2), is a new addition to the therapeutic armamentarium of glucose-lowering drugs. This review summarizes findings from different clinical and observational studies of canagliflozin 300 mg in patients with type 2 diabetes mellitus (T2DM). By inhibiting SGLT2, canagliflozin reduces reabsorption of filtered glucose, thereby increasing urinary glucose excretion in patients with T2DM...
January 2017: Indian Journal of Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28203358/the-renal-effects-of-sglt2-inhibitors-and-a-mini-review-of-the-literature
#17
REVIEW
Vasileios Andrianesis, Spyridoula Glykofridi, John Doupis
Sodium-glucose linked transporter 2 (SGLT2) inhibitors are a new and promising class of antidiabetic agents which target renal tubular glucose reabsorption. Their action is based on the blockage of SGLT2 sodium-glucose cotransporters that are located at the luminal membrane of tubular cells of the proximal convoluted tubule, inducing glucosuria. It has been proven that they significantly reduce glycated hemoglobin (HbA1c), along with fasting and postprandial plasma glucose in patients with type 2 diabetes mellitus (T2DM)...
December 2016: Therapeutic Advances in Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28178390/metabolic-and-hemodynamic-effects-of-sodium-dependent-glucose-co-transporter-2-inhibitors-on-cardio-renal-protection-in-the-treatment-of-patients-with-type-2-diabetes-mellitus
#18
REVIEW
Atsunori Kashiwagi, Hiroshi Maegawa
The specific Na+/glucose co-transporter 2 inhibitors (SGLT2 inhibitors) inhibit glucose reabsorption in proximal renal tubular cells, and both fasting and postprandial glucose significantly decrease due to urinary glucose loss. As a result, pancreatic β-cell function and peripheral insulin action significantly improve with relief from glucose toxicity. Furthermore, whole body energy metabolism changes to relative glucose deficiency and triggers increased lipolysis in fat cells, and fatty acid oxidation and then ketone body production in the liver during treatment with SGLT2 inhibitors...
February 8, 2017: Journal of Diabetes Investigation
https://www.readbyqxmd.com/read/28177279/sodium-glucose-co-transporter-2-inhibitors-and-their-nephroprotective-potential%C3%A2
#19
Natalia G Vallianou, Kyriakos Trigkidis, Christos Kazazis
Chronic kidney disease among patients with diabetes is on the rise. The sodium glucose co-transporters 2 inhibitors are a new class of glucose-lowering agents, which act through a novel mechanism by producing a decline in glucose reabsorption in the kidney, thereby increasing glucosuria and decreasing serum glucose levels. Data suggest that they possess nephroprotective properties. It is noteworthy that the efferent glomerular arteriole is 10 - 100 times more sensitive to the vasoconstrictive properties of angiotensin II than the afferent one and this might account for the consequently higher intra-glomerular capillary pressure, which is believed to be the cornerstone of diabetic nephropathy...
April 2017: Clinical Nephrology
https://www.readbyqxmd.com/read/28149983/role-of-the-kidney-in-type-2-diabetes-and-mechanism-of-action-of-sodium-glucose-cotransporter-2-inhibitors
#20
Matthew L Mintz
The aim of this supplement is to discuss the important role of the kidney in glucose homeostasis. It produces glucose via gluconeogenesis, it filters glucose from the blood, and reabsorbs the filtered glucose in the proximal tubule, mainly via the sodium-glucose cotransporter-2 (SGLT-2). SGLT-2 is paradoxically upregulated in individuals with type 2 diabetes (T2D), which results in increased glucose reabsorption and hyperglycemia. This core defect in the pathophysiology of T2D provides the rationale for the use of SGLT-2 inhibitors to increase urinary glucose excretion and reduce hyperglycemia in an insulin-independent manner...
December 2016: Journal of Family Practice
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