Abstract:
:An epidemic of obesity and type 2 diabetes is linked with the increase in consumption of fructose-containing sugars, such as sucrose and high-fructose corn syrup. In mammalian cells, fructose is metabolized predominantly via phosphorylation to fructose-1 phosphate by ketohexokinase (KHK) or by alternative pathways. Here we demonstrate that a KHK-dependent pathway mediates insulin resistance and inflammatory changes in the visceral fat in response to high fructose. We used mice (males, C57BL/6 background) including littermate wild-type control and mice lacking both isoforms of KHK (KHK-null). Fructose diet induced metabolic syndrome, including visceral obesity, insulin resistance, proinflammatory changes in the visceral fat (production of proinflammatory adipokines and macrophage infiltration), the endoplasmic reticulum stress signaling, and decrease of the high-molecular weight adiponectin followed by decrease in the downstream signaling. KHK-KO mice consuming the same high-fructose diet remained lean, with normal insulin sensitivity and healthy visceral adipose tissue with normal adiponectin function not distinguishable from the control by any of the tested parameters. This study demonstrates that blocking KHK and redirecting fructose metabolism to alternative pathways is an effective way to prevent visceral obesity and insulin resistance induced by high fructose, a widespread component of Western diets.
journal_name
Diabetesjournal_title
Diabetesauthors
Marek G,Pannu V,Shanmugham P,Pancione B,Mascia D,Crosson S,Ishimoto T,Sautin YYdoi
10.2337/db14-0411subject
Has Abstractpub_date
2015-02-01 00:00:00pages
508-18issue
2eissn
0012-1797issn
1939-327Xpii
db14-0411journal_volume
64pub_type
杂志文章相关文献
DIABETES文献大全abstract::NOD mice, a model strain for human type 1 diabetes, express proinsulin (PI) in the thymus. However, insulin-reactive T cells escape negative selection, and subsequent activation of the CD8(+) T-cell clonotype G9C8, which recognizes insulin B15-23 via an αβ T-cell receptor (TCR) incorporating TRAV8-1/TRAJ9 and TRBV19/T...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db15-1498
更新日期:2016-06-01 00:00:00
abstract::Hepatocyte growth factor (HGF) is a mitogen required for β-cell replication during pregnancy. To determine whether HGF/c-Met signaling is required for β-cell regeneration, we characterized mice with pancreatic deletion of the HGF receptor, c-Met (PancMet KO mice), in two models of reduced β-cell mass and regeneration:...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db13-0333
更新日期:2014-01-01 00:00:00
abstract::Methylglyoxal (MGO), a major precursor for advanced glycation end products, is increased in diabetes. In diabetic rodents, inhibition of MGO prevents cardiovascular disease (CVD). Whether plasma MGO levels are associated with incident CVD in people with type 1 diabetes is unknown. We included 159 individuals with pers...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db16-1578
更新日期:2017-08-01 00:00:00
abstract::Sirtuin 1 (SIRT1), an NAD(+)-dependent protein deacetylase, regulates a host of target proteins, including peroxisome proliferator-activated receptor (PPAR)-γ coactivator-1α (PGC-1α), a transcriptional coregulator that binds to numerous transcription factors in response to deacetylation to promote mitochondrial biogen...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db14-0325
更新日期:2015-02-01 00:00:00
abstract::Key parameters of the endocrine pancreas, such as islet number, islet mass, beta-cell mass, and alpha-cell mass, were studied in different strains of inbred mice to investigate the impact of genetic background on the size and structure of the endocrine pancreas. Six mice from each of seven different strains of inbred ...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.54.1.133
更新日期:2005-01-01 00:00:00
abstract::Impaired insulin secretion is a fundamental defect in type 2 diabetes. The aim of this study was to investigate whether single nucleotide polymorphisms (SNPs) in the genes regulating insulin secretion (SLC2A2 [encoding GLUT2], GCK, TCF1 [encoding HNF-1alpha], HNF4A, GIP, and GLP1R) are associated with the conversion f...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.54.7.2256
更新日期:2005-07-01 00:00:00
abstract::The introduction of 13C magnetic resonance spectroscopy (MRS) has enabled noninvasive measurement of muscle glycogen synthesis in humans. Conclusions based on measurements by the MRS technique assume that glucose metabolism in gastrocnemius muscle is representative for all skeletal muscles and thus can be extrapolated...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.54.5.1277
更新日期:2005-05-01 00:00:00
abstract::Lactate production, glucose utilization, glucose oxidation, and insulin release were studied in islets from rat and ob/ob mice. Lactate was determined with a highly sensitive method, based on esterification, subsequent separation, and quantitation with high-performance liquid chromatography. There was a significant la...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.47.8.1219
更新日期:1998-08-01 00:00:00
abstract::Leptin, encoded for by the mouse ob gene, regulates feeding behavior and energy metabolism. Its receptor (Ob-R) is encoded by the mouse diabetic (db) gene and is mutated in the db/db mouse so that it lacks the cytoplasmic domain. We show that the full-length leptin receptor (Ob-Rb), which is believed to transmit the l...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.46.2.313
更新日期:1997-02-01 00:00:00
abstract::The aim of this randomized double-blind study was to compare the within-subject variability of the glucose-lowering effect of a novel insulin analog, insulin detemir, with that of insulin glargine and NPH insulin in people with type 1 diabetes. Fifty-four subjects (32 males and 22 females, age 38 +/- 10 years [mean +/...
journal_title:Diabetes
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.2337/diabetes.53.6.1614
更新日期:2004-06-01 00:00:00
abstract::Many individuals with diabetes experience impaired cardiac contractility that cannot be explained by hypertension and atherosclerosis. This cardiomyopathy may be due to either organ-based damage, such as fibrosis, or to direct damage to cardiomyocytes. Reactive oxygen species (ROS) have been proposed to contribute to ...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.52.3.777
更新日期:2003-03-01 00:00:00
abstract:OBJECTIVE:The Diabetes Control and Complications Trial (Diabetes 44:968-983, 1995) presented statistical models suggesting that subjects with similar A1C levels had a higher risk of retinopathy progression in the conventional treatment group than in the intensive treatment group. That analysis has been cited to support...
journal_title:Diabetes
pub_type: 杂志文章,随机对照试验
doi:10.2337/db07-1618
更新日期:2008-04-01 00:00:00
abstract::Acute elevations of plasma free fatty acid (FFA) levels augment glucose-stimulated insulin secretion (GSIS). Prolonged elevations of FFA levels reportedly impair GSIS, but no one has previously compared GSIS after prolonged exposure to saturated or unsaturated fat. Rats received a low-fat diet (Low-Fat) or one enriche...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.51.6.1825
更新日期:2002-06-01 00:00:00
abstract::The IgG from a patient (Italy 2 [I2]) with hypoglycemia, due to autoantibodies to the insulin receptor, was purified on protein A Sepharose into two fractions that were tested in various human tissues and cells. The IgG fraction that bound protein A (absorbed IgG [IgGa]) nearly completely inhibited the binding of 125I...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.41.1.6
更新日期:1992-01-01 00:00:00
abstract::Peroxisome proliferator-activated receptor (PPAR)gamma is a key transcription factor facilitating fat deposition in adipose tissue through its proadipogenic and lipogenic actions. Human patients with dominant-negative mutations in PPARgamma display lipodystrophy and extreme insulin resistance. For this reason it was c...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db06-0389
更新日期:2006-10-01 00:00:00
abstract::By closing ATP-sensitive K+ (K+-ATP) channels, glucose promotes depolarization-dependent Ca2+ entry and cytoplasmic free Ca2+ concentration ([Ca2+]i) rise in beta-cells. Ca2+-dependent exocytosis of insulin granules is then potentiated by a K+-ATP channel-independent action of glucose. The underlying mechanisms of thi...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.47.11.1713
更新日期:1998-11-01 00:00:00
abstract::Diabetic states are characterized by a raised serum/islet level of triglycerides and a lowered EC50 (concentration at half-maximal stimulation) for glucose-induced insulin secretion. Culturing islets with long-chain fatty acids (FAs) replicates the basal insulin hypersecretion. In a previous study, we showed that the ...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.47.12.1889
更新日期:1998-12-01 00:00:00
abstract:OBJECTIVE:Elevated fasting glucose level is associated with increased carotid intima-media thickness (IMT), a measure of subclinical atherosclerosis. It is unclear if this association is causal. Using the principle of Mendelian randomization, we sought to explore the causal association between circulating glucose and I...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db10-0839
更新日期:2011-01-01 00:00:00
abstract::Mutations in several genes cause nonautoimmune diabetes, but numerous patients still have unclear genetic defects, hampering our understanding of the development of the disease and preventing pathogenesis-oriented treatment. We used whole-genome sequencing with linkage analysis to study a consanguineous family with ea...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db13-1784
更新日期:2014-10-01 00:00:00
abstract::Islet transplantation is a promising treatment for type 1 diabetes. However, islet grafts are submitted to multiple injuries, including immunosuppressive drug toxicity, hyperglycemia, hypoxia, unspecific inflammatory reactions, as well as allo- and autoimmune destruction. Therapeutic approaches to these damage mechani...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.51.3.557
更新日期:2002-03-01 00:00:00
abstract::Type 2 diabetes is characterized by increased plasma triglyceride levels and a fourfold increase in ischemic heart disease, but the mechanism is unclear. CD36 is a receptor/transporter that binds fatty acids of lipoproteins. CD36 deficiency has been linked with insulin resistance. There is strong evidence of in vivo i...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.52.5.1248
更新日期:2003-05-01 00:00:00
abstract:OBJECTIVE:Sarco-endoplasmic reticulum Ca(2+)-ATPase 2b (SERCA2b) and SERCA3 pump Ca(2+) in the endoplasmic reticulum (ER) of pancreatic β-cells. We studied their role in the control of the free ER Ca(2+) concentration ([Ca(2+)](ER)) and the role of SERCA3 in the control of insulin secretion and ER stress. RESEARCH DES...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db10-1543
更新日期:2011-10-01 00:00:00
abstract::Because the pathogenetic understanding of diabetic vascular complications remains fragmentary, and even the best available interventions may prove insufficient to arrest the progression of certain lesions, new avenuses of investigation should be pursued. One of these should be the early in vivo investigation of the ce...
journal_title:Diabetes
pub_type: 杂志文章,评审
doi:10.2337/diab.40.6.653
更新日期:1991-06-01 00:00:00
abstract:OBJECTIVE:Pregnancy induces a state of immunological tolerance that aims at suppressing immune responses against the fetus and has been linked to temporal remission of preexisting autoimmune disorders. To understand the mechanisms of this reversible immune regulation, we investigated the role of a key pregnancy hormone...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db06-1727
更新日期:2007-06-01 00:00:00
abstract::NIDDM has a substantial genetic component, but the nature of the genetic susceptibility is largely unknown. Maturity-onset diabetes of the young (MODY) is a genetically heterogeneous monogenic form of NIDDM characterized by an early age of onset and autosomal dominant inheritance, and linkage studies have identified g...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.47.11.1793
更新日期:1998-11-01 00:00:00
abstract::Plasma glucagon response to glucose in diabetic subjects was observed before and after treatment. In normal subjects, plasma glucagon concentrations decreased substantially after an oral glucose load. In all diabetic patients before treatment, plasma glucagon was not suppressed and rather tended to rise paradoxically ...
journal_title:Diabetes
pub_type: 临床试验,杂志文章
doi:10.2337/diab.27.12.1145
更新日期:1978-12-01 00:00:00
abstract::The hypoglycemic activity of the synthetic peptide fragment of human growth hormone, hGH 1--15, is insulin dependent, although it does not alter the circulating levels of plasma insulin in normal and diabetic rats. In severe diabetes induced by streptozotocin, the peptide had no effect on the basal levels of blood glu...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.28.12.1126
更新日期:1979-12-01 00:00:00
abstract::Fed male Wistar rats were eviscerated by two procedures. The first group of eviscerated rats were left with a nonfunctional liver in situ while the second group were eviscerated by a newer technic, developed in this laboratory, that preserves liver function. The animals were maintained on a regimen of saline and antib...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.24.7.637
更新日期:1975-07-01 00:00:00
abstract::Evaluation of the existence of a diurnal pattern of glucose tolerance after mixed meals is important to inform a closed-loop system of treatment for insulin requiring diabetes. We studied 20 healthy volunteers with normal fasting glucose (4.8 ± 0.1 mmol/L) and HbA(1c) (5.2 ± 0.0%) to determine such a pattern in nondia...
journal_title:Diabetes
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.2337/db11-1478
更新日期:2012-11-01 00:00:00
abstract::The soluble plant fiber psyllium significantly reduced fasting glucose and total cholesterol levels in the C57BL/KsJ db/db diabetic mouse relative to placebo-fed mice. Insulin levels were significantly higher in psyllium-fed than placebo-fed animals, indicating this fiber may delay the progression of diabetes in the a...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.38.12.1528
更新日期:1989-12-01 00:00:00