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https://www.readbyqxmd.com/read/27639082/exenatide-improves-both-hepatic-and-adipose-tissue-insulin-resistance-a-dynamic-pet-study
#1
Amalia Gastaldelli, Melania Gaggini, Giuseppe Daniele, Demetrio Ciociaro, Eugenio Cersosimo, Devjit Tripathy, Curtis Triplitt, Peter Fox, Nicolas Musi, Ralph DeFronzo, Patricia Iozzo
: GLP-1 receptor agonists (GLP-1-RAs) act on multiple tissues, in addition to the pancreas. Recent studies suggest that GLP-1-RAs act on liver and adipose tissue to reduce insulin resistance (IR). Thus, we evaluated the acute effects of exenatide (EX) on hepatic (Hep-IR) and adipose (Adipo-IR) insulin resistance and glucose uptake. 15 male subjects (age=56±8 y, BMI=29±1 kg/m(2) , A1c=5.7±0.1%) were studied on two occasions, with a double blind subcutaneous injection of exenatide (5 mcg) or placebo (PLC) 30 min before a 75-gram oral glucose tolerance test (OGTT)...
September 17, 2016: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/26116695/exenatide-regulates-cerebral-glucose-metabolism-in-brain-areas-associated-with-glucose-homeostasis-and-reward-system
#2
RANDOMIZED CONTROLLED TRIAL
Giuseppe Daniele, Patricia Iozzo, Marjorie Molina-Carrion, Jack Lancaster, Demetrio Ciociaro, Eugenio Cersosimo, Devjit Tripathy, Curtis Triplitt, Peter Fox, Nicolas Musi, Ralph DeFronzo, Amalia Gastaldelli
Glucagon-like peptide 1 receptors (GLP-1Rs) have been found in the brain, but whether GLP-1R agonists (GLP-1RAs) influence brain glucose metabolism is currently unknown. The study aim was to evaluate the effects of a single injection of the GLP-1RA exenatide on cerebral and peripheral glucose metabolism in response to a glucose load. In 15 male subjects with HbA1c of 5.7 ± 0.1%, fasting glucose of 114 ± 3 mg/dL, and 2-h glucose of 177 ± 11 mg/dL, exenatide (5 μg) or placebo was injected in double-blind, randomized fashion subcutaneously 30 min before an oral glucose tolerance test (OGTT)...
October 2015: Diabetes
https://www.readbyqxmd.com/read/25425451/initial-combination-therapy-with-metformin-pioglitazone-and-exenatide-is-more-effective-than-sequential-add-on-therapy-in-subjects-with-new-onset-diabetes-results-from-the-efficacy-and-durability-of-initial-combination-therapy-for-type-2-diabetes-edict-a-randomized
#3
RANDOMIZED CONTROLLED TRIAL
M A Abdul-Ghani, C Puckett, C Triplitt, D Maggs, J Adams, E Cersosimo, R A DeFronzo
AIM: To test our hypothesis that initiating therapy with a combination of agents known to improve insulin secretion and insulin sensitivity in subjects with new-onset diabetes would produce greater, more durable reduction in glycated haemoglobin (HbA1c) levels, while avoiding hypoglycaemia and weight gain, compared with sequential addition of agents that lower plasma glucose but do not correct established pathophysiological abnormalities. METHODS: Drug-naïve, recently diagnosed subjects with type 2 diabetes mellitus (T2DM) were randomized in an open-fashion design in a single-centre study to metformin/pioglitazone/exenatide (triple therapy; n = 106) or an escalating dose of metformin followed by sequential addition of sulfonylurea and glargine insulin (conventional therapy; n = 115) to maintain HbA1c levels at <6...
March 2015: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/25138792/acute-insulin-resistance-stimulates-and-insulin-sensitization-attenuates-vascular-smooth-muscle-cell-migration-and-proliferation
#4
Eugenio Cersosimo, Xiaojing Xu, Sikarin Upala, Curtis Triplitt, Nicolas Musi
UNLABELLED: Differential activation/deactivation of insulin signaling, PI-3K and MAP-K pathways by high glucose and palmitate, with/out the insulin sensitizer pioglitazone (PIO), have been previously shown in vascular smooth muscle cells (VSMCs). To determine the biological impact of these molecular changes, we examined VSMC migration and proliferation ("M"&"P") patterns in similar conditions. VSMCs from healthy human coronary arteries were incubated in growth medium and "M"&"P" were analyzed after exposure to high glucose (25 mmol/L) ± palmitate (200 μmol/L) and ± PIO (8 μmol/L) for 5 h...
August 1, 2014: Physiological Reports
https://www.readbyqxmd.com/read/24676619/inhibition-of-renal-glucose-reabsorption-as-a-novel-treatment-for-diabetes-patients
#5
REVIEW
Eugenio Cersosimo, Carolina Solis-Herrera, Curtis Triplitt
UNLABELLED: The importance of the kidney in glucose homeostasis has been recognized for many years. Recent observations indicating a greater role of renal glucose metabolism in various physiologic and pathologic conditions have rekindled the interest in renal glucose handling as a potential target for the treatment of diabetes. The enormous capacity of the proximal tubular cells to reabsorb the filtered glucose load entirely, utilizing the sodium-glucose co-transporter system (primarily SGLT-2), became the focus of attention...
January 2014: Jornal Brasileiro de Nefrologia: ʹorgão Oficial de Sociedades Brasileira e Latino-Americana de Nefrologia
https://www.readbyqxmd.com/read/24524730/assessment-of-pancreatic-%C3%AE-cell-function-review-of-methods-and-clinical-applications
#6
REVIEW
Eugenio Cersosimo, Carolina Solis-Herrera, Michael E Trautmann, Jaret Malloy, Curtis L Triplitt
Type 2 diabetes mellitus (T2DM) is characterized by a progressive failure of pancreatic β-cell function (BCF) with insulin resistance. Once insulin over-secretion can no longer compensate for the degree of insulin resistance, hyperglycemia becomes clinically significant and deterioration of residual β-cell reserve accelerates. This pathophysiology has important therapeutic implications. Ideally, therapy should address the underlying pathology and should be started early along the spectrum of decreasing glucose tolerance in order to prevent or slow β-cell failure and reverse insulin resistance...
January 2014: Current Diabetes Reviews
https://www.readbyqxmd.com/read/23736306/genetic-epidemiology-of-cardiometabolic-risk-factors-and-their-clustering-patterns-in-mexican-american-children-and-adolescents-the-safari-study
#7
Sharon P Fowler, Sobha Puppala, Rector Arya, Geetha Chittoor, Vidya S Farook, Jennifer Schneider, Roy G Resendez, Ram Prasad Upadhayay, Jane Vandeberg, Kelly J Hunt, Benjamin Bradshaw, Eugenio Cersosimo, John L Vandeberg, Laura Almasy, Joanne E Curran, Anthony G Comuzzie, Donna M Lehman, Christopher P Jenkinson, Jane L Lynch, Ralph A Defronzo, John Blangero, Daniel E Hale, Ravindranath Duggirala
Pediatric metabolic syndrome (MS) and its cardiometabolic components (MSCs) have become increasingly prevalent, yet little is known about the genetics underlying MS risk in children. We examined the prevalence and genetics of MS-related traits among 670 non-diabetic Mexican American (MA) children and adolescents, aged 6-17 years (49 % female), who were participants in the San Antonio Family Assessment of Metabolic Risk Indicators in Youth study. These children are offspring or biological relatives of adult participants from three well-established Mexican American family studies in San Antonio, TX, at increased risk of type 2 diabetes...
September 2013: Human Genetics
https://www.readbyqxmd.com/read/23671849/short-term-exercise-training-improves-insulin-sensitivity-but-does-not-inhibit-inflammatory-pathways-in-immune-cells-from-insulin-resistant-subjects
#8
Sara M Reyna, Puntip Tantiwong, Eugenio Cersosimo, Ralph A Defronzo, Apiradee Sriwijitkamol, Nicolas Musi
Background. Exercise has an anti-inflammatory effect against, and immune cells play critical roles in the development, of insulin resistance and atherosclerotic vascular disease (AVD). Thus, the goal of this study was to determine whether exercise improves insulin sensitivity in insulin-resistant subjects by downregulating proinflammatory signaling in immune cells. Methods. Seventeen lean, 8 obese nondiabetic, and 11 obese type 2 diabetic individuals underwent an aerobic exercise program for 15 days and an insulin clamp before and after exercise...
2013: Journal of Diabetes Research
https://www.readbyqxmd.com/read/23579178/mechanisms-of-glucose-lowering-of-dipeptidyl-peptidase-4-inhibitor-sitagliptin-when-used-alone-or-with-metformin-in-type-2-diabetes-a-double-tracer-study
#9
RANDOMIZED CONTROLLED TRIAL
Carolina Solis-Herrera, Curtis Triplitt, Jose de Jesús Garduno-Garcia, John Adams, Ralph A DeFronzo, Eugenio Cersosimo
OBJECTIVE: To assess glucose-lowering mechanisms of sitagliptin (S), metformin (M), and the two combined (M+S). RESEARCH DESIGN AND METHODS: We randomized 16 patients with type 2 diabetes mellitus (T2DM) to four 6-week treatments with placebo (P), M, S, and M+S. After each period, subjects received a 6-h meal tolerance test (MTT) with [(14)C]glucose to calculate glucose kinetics. Fasting plasma glucose (FPG), fasting plasma insulin, C-peptide (insulin secretory rate [ISR]), fasting plasma glucagon, and bioactive glucagon-like peptide (GLP-1) and gastrointestinal insulinotropic peptide (GIP) were measured...
September 2013: Diabetes Care
https://www.readbyqxmd.com/read/22094332/potential-role-of-insulin-signaling-on-vascular-smooth-muscle-cell-migration-proliferation-and-inflammation-pathways
#10
Eugenio Cersosimo, Xiaojing Xu, Nicolas Musi
To investigate the role of insulin signaling pathways in migration, proliferation, and inflammation of vascular smooth muscle cells (VSMCs), we examined the expression of active components of the phosphatidyl inositol 3 (PI-3) kinase (p-Akt) and mitogen-activated protein kinase (MAPK) (p-Erk) in primary cultures of VSMCs from human coronary arteries. VSMCs were treated in a dose-response manner with insulin (0, 1, 10, and 100 nM) for 20 min, and Akt and Erk phosphorylation were measured by Western blot analysis...
February 15, 2012: American Journal of Physiology. Cell Physiology
https://www.readbyqxmd.com/read/21939794/improving-treatment-in-hispanic-latino-patients
#11
Eugenio Cersosimo, Nicolas Musi
The prevalence of type 2 diabetes mellitus is higher in Hispanic/Latino individuals living in the United States compared with their non-Hispanic white counterparts. Many factors contribute to the increased prevalence of type 2 diabetes, including biological characteristics, socioeconomic conditions, and cultural aspects. The contribution of genetics to the risk of type 2 diabetes in Hispanic/Latino patients is becoming increasingly clear, but this inherent risk factor cannot be modified. However, certain socioeconomic and cultural factors, such as reduced access to healthcare, language barriers, cultural beliefs, and lack of cultural competence by the healthcare provider, are modifiable and should be overcome in order to improve the management of type 2 diabetes in Hispanic/Latino patients...
October 2011: American Journal of Medicine
https://www.readbyqxmd.com/read/20859539/pioglitazone-and-alogliptin-combination-therapy-in-type-2-diabetes-a-pathophysiologically-sound-treatment
#12
REVIEW
Curtis Triplitt, Eugenio Cersosimo, Ralph A DeFronzo
Insulin resistance and islet (beta and alpha) cell dysfunction are major pathophysiologic abnormalities in type 2 diabetes mellitus (T2DM). Pioglitazone is a potent insulin sensitizer, improves pancreatic beta cell function and has been shown in several outcome trials to lower the risk of atherosclerotic and cardiovascular events. Glucagon-like peptide-1 deficiency/resistance contributes to islet cell dysfunction by impairing insulin secretion and increasing glucagon secretion. Dipeptidyl peptidase-4 (DPP-4) inhibitors improve pancreatic islet function by augmenting glucose-dependent insulin secretion and decreasing elevated plasma glucagon levels...
2010: Vascular Health and Risk Management
https://www.readbyqxmd.com/read/20739506/nf-%C3%AE%C2%BAb-activity-in-muscle-from-obese-and-type-2-diabetic-subjects-under-basal-and-exercise-stimulated-conditions
#13
Puntip Tantiwong, Karthigayan Shanmugasundaram, Adriana Monroy, Sangeeta Ghosh, Mengyao Li, Ralph A DeFronzo, Eugenio Cersosimo, Apiradee Sriwijitkamol, Sumathy Mohan, Nicolas Musi
NF-κB is a transcription factor that controls the gene expression of several proinflammatory proteins. Cell culture and animal studies have implicated increased NF-κB activity in the pathogenesis of insulin resistance and muscle atrophy. However, it is unclear whether insulin-resistant human subjects have abnormal NF-κB activity in muscle. The effect that exercise has on NF-κB activity/signaling also is not clear. We measured NF-κB DNA-binding activity and the mRNA level of putative NF-κB-regulated myokines interleukin (IL)-6 and monocyte chemotactic protein-1 (MCP-1) in muscle samples from T2DM, obese, and lean subjects immediately before, during (40 min), and after (210 min) a bout of moderate-intensity cycle exercise...
November 2010: American Journal of Physiology. Endocrinology and Metabolism
https://www.readbyqxmd.com/read/20455891/pioglitazone-improvement-of-fasting-and-postprandial-hyperglycaemia-in-mexican-american-patients-with-type-2-diabetes-a-double-tracer-ogtt-study
#14
Leonard C Glass, Kenneth Cusi, Rachele Berria, Roberta Petz, Eugenio Cersosimo, Ralph A Defronzo, Amalia Gastaldelli
OBJECTIVES: By using tracer techniques, we explored the metabolic mechanisms by which pioglitazone treatment for 16 weeks improves oral glucose tolerance in patients with type 2 diabetes when compared to subjects without diabetes. METHODS: In all subjects, before and after treatment, we measured rates of tissue glucose clearance (MCR), oral glucose appearance (RaO) and endogenous glucose production (EGP) during a (4-h) double tracer oral glucose tolerance test (OGTT) (1-(14)C-glucose orally and 3-(3)H-glucose intravenously)...
September 2010: Clinical Endocrinology
https://www.readbyqxmd.com/read/18983329/chronic-low-dose-lipid-infusion-in-healthy-patients-induces-markers-of-endothelial-activation-independent-of-its-metabolic-effects
#15
COMPARATIVE STUDY
Sangeeta R Kashyap, Renata Belfort, Eugenio Cersosimo, Shuko Lee, Kenneth Cusi
Elevated plasma triglyceride/free fatty acid (FFA) levels and insulin resistance may promote atherosclerosis through endothelial activation (ie, increased expression of intercellular adhesion molecule 1 [ICAM-1]/vascular adhesion molecule 1 [VCAM-1], and endothelin-1 [ET-1]) in patients with the metabolic syndrome, but this has never been directly tested. The authors measured endothelial activation and insulin sensitivity (euglycemic insulin clamp with [3-(3)H]-glucose) after a 4-day low-dose lipid infusion that elevated plasma FFA to levels observed in the metabolic syndrome in 20 lean, non-diabetic insulin-resistant subjects with a strong family history of type 2 diabetes mellitus (FH(+)) and 10 insulin-sensitive volunteers without a family history of type 2 diabetes mellitus (FH(-))...
2008: Journal of the Cardiometabolic Syndrome
https://www.readbyqxmd.com/read/18633101/elevated-toll-like-receptor-4-expression-and-signaling-in-muscle-from-insulin-resistant-subjects
#16
Sara M Reyna, Sangeeta Ghosh, Puntip Tantiwong, C S Reddy Meka, Phyllis Eagan, Christopher P Jenkinson, Eugenio Cersosimo, Ralph A Defronzo, Dawn K Coletta, Apiradee Sriwijitkamol, Nicolas Musi
OBJECTIVE- Tall-like receptor (TLR)4 has been implicated in the pathogenesis of free fatty acid (FFA)-induced insulin resistance by activating inflammatory pathways, including inhibitor of kappaB (IkappaB)/nuclear factor kappaB (NFkappaB). However, it is not known whether insulin-resistant subjects have abnormal TLR4 signaling. We examined whether insulin-resistant subjects have abnormal TLR4 expression and TLR4-driven (IkappaB/NFkappaB) signaling in skeletal muscle. RESEARCH DESIGN AND METHODS- TLR4 gene expression and protein content were measured in muscle biopsies in 7 lean, 8 obese, and 14 type 2 diabetic subjects...
October 2008: Diabetes
https://www.readbyqxmd.com/read/18334612/mechanism-of-action-of-exenatide-to-reduce-postprandial-hyperglycemia-in-type-2-diabetes
#17
Antonio Cervera, Estela Wajcberg, Apiradee Sriwijitkamol, Marianella Fernandez, Pengou Zuo, Curtis Triplitt, Nicolas Musi, Ralph A DeFronzo, Eugenio Cersosimo
We examined the contributions of insulin secretion, glucagon suppression, splanchnic and peripheral glucose metabolism, and delayed gastric emptying to the attenuation of postprandial hyperglycemia during intravenous exenatide administration. Twelve subjects with type 2 diabetes (3 F/9 M, 44 +/- 2 yr, BMI 34 +/- 4 kg/m2, Hb A(1c) 7.5 +/- 1.5%) participated in three meal-tolerance tests performed with double tracer technique (iv [3-3H]glucose and oral [1-14C]glucose): 1) iv saline (CON), 2) iv exenatide (EXE), and 3) iv exenatide plus glucagon (E+G)...
May 2008: American Journal of Physiology. Endocrinology and Metabolism
https://www.readbyqxmd.com/read/17909084/addition-of-pioglitazone-and-ramipril-to-intensive-insulin-therapy-in-type-2-diabetic-patients-improves-vascular-dysfunction-by-different-mechanisms
#18
RANDOMIZED CONTROLLED TRIAL
Marianella Fernandez, Curtis Triplitt, Estela Wajcberg, Apiradee A Sriwijilkamol, Nicholas Musi, Kenneth Cusi, Ralph DeFronzo, Eugenio Cersosimo
OBJECTIVE: We examined the relationship between glycemic control, vascular reactivity, and inflammation in type 2 diabetic subjects. RESEARCH DESIGN AND METHODS: Thirty subjects with type 2 diabetes were initiated on intensive insulin therapy (continuous subcutaneous insulin infusion [n = 12] or multiple daily injections [n = 18]) and then randomized to either pioglitazone (PIO group;45 mg/day), ramipril (RAM group; 10 mg/day), or placebo (PLC group) for 36 weeks...
January 2008: Diabetes Care
https://www.readbyqxmd.com/read/17681171/relationship-between-hepatic-visceral-fat-and-hepatic-insulin-resistance-in-nondiabetic-and-type-2-diabetic-subjects
#19
COMPARATIVE STUDY
Amalia Gastaldelli, Kenneth Cusi, Maura Pettiti, Jean Hardies, Yoshinori Miyazaki, Rachele Berria, Emma Buzzigoli, Anna Maria Sironi, Eugenio Cersosimo, Ele Ferrannini, Ralph A Defronzo
BACKGROUND AND AIMS: Abdominal fat accumulation (visceral/hepatic) has been associated with hepatic insulin resistance (IR) in obesity and type 2 diabetes (T2DM). We examined the relationship between visceral/hepatic fat accumulation and hepatic IR/accelerated gluconeogenesis (GNG). METHODS: In 14 normal glucose tolerant (NGT) (body mass index [BMI] = 25 +/- 1 kg/m(2)) and 43 T2DM (24 nonobese, BMI = 26 +/- 1; 19 obese, BMI = 32 +/- 1 kg/m(2)) subjects, we measured endogenous (hepatic) glucose production (3-(3)H-glucose) and GNG ((2)H(2)O) in the basal state and during 240 pmol/m(2)/min euglycemic-hyperinsulinemic clamp, and liver (LF) subcutaneous (SAT)/visceral (VAT) fat content by magnetic resonance spectroscopy/magnetic resonance imaging...
August 2007: Gastroenterology
https://www.readbyqxmd.com/read/17327455/effect-of-acute-exercise-on-ampk-signaling-in-skeletal-muscle-of-subjects-with-type-2-diabetes-a-time-course-and-dose-response-study
#20
Apiradee Sriwijitkamol, Dawn K Coletta, Estela Wajcberg, Gabriela B Balbontin, Sara M Reyna, John Barrientes, Phyllis A Eagan, Christopher P Jenkinson, Eugenio Cersosimo, Ralph A DeFronzo, Kei Sakamoto, Nicolas Musi
Activation of AMP-activated protein kinase (AMPK) by exercise induces several cellular processes in muscle. Exercise activation of AMPK is unaffected in lean (BMI approximately 25 kg/m(2)) subjects with type 2 diabetes. However, most type 2 diabetic subjects are obese (BMI >30 kg/m(2)), and exercise stimulation of AMPK is blunted in obese rodents. We examined whether obese type 2 diabetic subjects have impaired exercise stimulation of AMPK, at different signaling levels, spanning from the upstream kinase, LKB1, to the putative AMPK targets, AS160 and peroxisome proliferator-activated receptor coactivator (PGC)-1alpha, involved in glucose transport regulation and mitochondrial biogenesis, respectively...
March 2007: Diabetes
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