Yoshio Nagai
Yale University
EndocrinologyLipogenesisInsulin resistanceInsulinBiology
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Publications 19
#1Takashi UzuH-Index: 38
#2Shin-ichi ArakiH-Index: 39
Last. Hiroshi MaegawaH-Index: 48
view all 23 authors...
In patients with diabetes, albuminuria is a risk marker of end-stage renal disease and cardiovascular events. An increased renin-angiotensin system activity has been reported to play an important role in the pathological processes in these conditions. We compared the effect of aliskiren, a direct renin inhibitor (DRI), with that of angiotensin receptor blockers (ARBs) on albuminuria and urinary excretion of angiotensinogen, a marker of intrarenal renin-angiotensin system activity.We randomly ass...
6 CitationsSource
#1Masateru Ushio (Shiga University of Medical Science)H-Index: 1
#2Yoshihiko Nishio (Kadai: Kagoshima University)H-Index: 37
Last. Hiroshi Maegawa (Shiga University of Medical Science)H-Index: 48
view all 11 authors...
Nonalcoholic fatty liver disease is the most frequent liver disease. Ezetimibe, an inhibitor of intestinal cholesterol absorption, has been reported to ameliorate hepatic steatosis in human and animal models. To explore how ezetimibe reduces hepatic steatosis, we investigated the effects of ezetimibe on the expression of lipogenic enzymes and intestinal lipid metabolism in mice fed a high-fat or a high-fructose diet. CBA/JN mice were fed a high-fat diet or a high-fructose diet for 8 wk with or w...
24 CitationsSource
#1Derek M. Erion (Yale University)H-Index: 21
#2Maya E. KotasH-Index: 11
Last. Matthew P. Gillum (Roy J. and Lucille A. Carver College of Medicine)H-Index: 9
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Abstract cAMP-responsive element-binding protein (CREB)-regulated transcription coactivator 2 (CRTC2) regulates transcription of gluconeogenic genes by specifying targets for the transcription factor CREB in response to glucagon. We used an antisense oligonucleotide directed against CRTC2 in both normal rodents and in rodent models of increased gluconeogenesis to better understand the role of CRTC2 in metabolic disease. In the context of severe hyperglycemia and elevated hepatic glucose producti...
9 CitationsSource
#1Derek M. Erion (Yale University)H-Index: 21
#2Violetta Popov (Yale University)H-Index: 1
Last. Varman T. Samuel (Yale University)H-Index: 48
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By 2030, nearly half of Americans will have nonalcoholic fatty liver disease. In part, this epidemic is fueled by the increasing consumption of caloric sweeteners coupled with an innate capacity to convert sugar into fat via hepatic de novo lipogenesis. In addition to serving as substrates, monosaccharides also increase the expression of key enzymes involved in de novo lipogenesis via the carbohydrate response element-binding protein (ChREBP). To determine whether ChREBP is a potential therapeut...
41 CitationsSource
#1Dirk Weismann (Yale University)H-Index: 7
#2Derek M. Erion (Yale University)H-Index: 21
Last. Varman T. Samuel (Yale University)H-Index: 48
view all 18 authors...
Aims/hypothesis Insulin action is purportedly modulated by Drosophila tribbles homologue 3 (TRIB3), which in vitro prevents thymoma viral proto-oncogene (AKT) and peroxisome proliferator-activated receptor-γ (PPAR-γ) activation. However, the physiological impact of TRIB3 action in vivo remains controversial.
17 CitationsSource
#1Derek M. Erion (Yale University)H-Index: 21
#2Irena D. Ignatova (Yale University)H-Index: 1
Last. Gerald I. Shulman (Yale University)H-Index: 144
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Summary In patients with poorly controlled type 2 diabetes mellitus (T2DM), hepatic insulin resistance and increased gluconeogenesis contribute to fasting and postprandial hyperglycemia. Since cAMP response element-binding protein (CREB) is a key regulator of gluconeogenic gene expression, we hypothesized that decreasing hepatic CREB expression would reduce fasting hyperglycemia in rodent models of T2DM. In order to test this hypothesis, we used a CREB-specific antisense oligonucleotide (ASO) to...
60 CitationsSource
#1Satoshi UgiH-Index: 7
#2Kun ShiH-Index: 7
Last. Hiroshi MaegawaH-Index: 48
view all 16 authors...
Protein-tyrosine phosphatase 1B (PTP1B) is a major regulator of insulin sensitivity. We have described a novel action of PTP1B in the induction of sterol regulatory element-binding protein-1 (SREBP-1) gene expression through activation of protein phosphatase 2A (PP2A). PTP1B is anchored to the endoplasmic reticulum membrane via its C-terminal tail. We have previously reported that membrane localization of PTP1B is essential for PP2A activation, which is crucial for enhancing SREBP-1 gene express...
10 CitationsSource
Hepatic gluconeogenesis is a major contributing factor to hyperglycemia in the fasting and postprandial states in type 2 diabetes mellitus (T2DM). Because Sirtuin 1 (SirT1) induces hepatic gluconeogenesis during fasting through the induction of phosphoenolpyruvate carboxylase kinase (PEPCK), fructose-1,6-bisphosphatase (FBPase), and glucose-6-phosphatase (G6Pase) gene transcription, we hypothesized that reducing SirT1, by using an antisense oligonucleotide (ASO), would decrease fasting hyperglyc...
138 CitationsSource
#1Yoshio Nagai (Yale University)H-Index: 15
#2Shin Yonemitsu (Yale University)H-Index: 17
Last. Gerald I. Shulman (Yale University)H-Index: 144
view all 18 authors...
Summary Peroxisome proliferator-activated receptor γ coactivator-1 β (PGC-1β) is known to be a transcriptional coactivator for SREBP-1, the master regulator of hepatic lipogenesis. Here, we evaluated the role of PGC-1β in the pathogenesis of fructose-induced insulin resistance by using an antisense oligonucletoide (ASO) to knockdown PGC-1β in liver and adipose tissue. PGC-1β ASO improved the metabolic phenotype induced by fructose feeding by reducing expression of SREBP-1 and downstream lipogeni...
141 CitationsSource
#1Katsutaro MorinoH-Index: 26
#2Susanne NeschenH-Index: 28
Last. Gerald I. ShulmanH-Index: 144
view all 13 authors...
OBJECTIVE—Insulin resistance in skeletal muscle plays a critical role in the pathogenesis of type 2 diabetes, yet the cellular mechanisms responsible for insulin resistance are poorly understood. In this study, we examine the role of serine phosphorylation of insulin receptor substrate (IRS)-1 in mediating fat-induced insulin resistance in skeletal muscle in vivo. RESEARCH DESIGN AND METHODS—To directly assess the role of serine phosphorylation in mediating fat-induced insulin resistance in skel...
100 CitationsSource