Time-dependent effects of free fatty acids on glucose effectiveness in type 2 diabetes.


:Impaired effectiveness of glucose to suppress endogenous glucose production (EGP) is an important cause of worsening hyperglycemia in type 2 diabetes. Elevated free fatty acids (FFAs) may impair glucose effectiveness via several mechanisms, including rapid changes in metabolic fluxes and/or more gradual changes in gene expression of key enzymes or other proteins. Thus, we examined the magnitude and time course of effects of FFAs on glucose effectiveness in type 2 diabetes and whether glucose effectiveness can be restored by lowering FFAs. Glucose fluxes ([3-(3)H]-glucose) were measured during 6-h pancreatic clamp studies, at euglycemia (5 mmol/l glucose, t=0-240 min), and hyperglycemia (10 mmol/l, t=240-360 min). We studied 19 poorly controlled subjects with type 2 diabetes (HbA(1c) 10.9 +/- 0.4%, age 50 +/- 3 years, BMI 30 +/- 2 kg/m(2)) on at least two occasions with saline (NA- group) or nicotinic acid (NA group) infusions for 3, 6, or 16 h (NA3h, NA6h, and NA16h groups, respectively) to lower FFAs to nondiabetic levels. As a reference group, glucose effectiveness was also assessed in 15 nondiabetic subjects. There was rapid improvement in hepatic glucose effectiveness following only 3 h of NA infusion (NA3h = 31 +/- 6% suppression of EGP with hyperglycemia vs. NA- = 8 +/- 7%; P<0.01) and complete restoration of glucose effectiveness after 6 h of NA (NA6h = 41 +/- 8% suppression of EGP; P = NS vs. nondiabetic subjects). Importantly, the loss of hepatic glucose effectiveness in type 2 diabetes is completely reversible upon correcting the increased FFA concentrations. A longer duration of FFA lowering may be required to overcome the chronic effects of increased FFAs on hepatic glucose effectiveness.






Kishore P,Tonelli J,Koppaka S,Fratila C,Bose A,Lee DE,Reddy K,Hawkins M




Has Abstract


2006-06-01 00:00:00
















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    abstract::We have recently reported an A to G transition at nucleotide position 3243 in the mitochondrial DNA (mtDNA) tRNA(Leu(UUR)) gene in a large family with non-insulin-dependent diabetes mellitus (NIDDM). Characteristic was its maternal transmission and an associated sensorineural hearing loss. In a screening of a Dutch an...


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    authors: van den Ouweland JM,Lemkes HH,Trembath RC,Ross R,Velho G,Cohen D,Froguel P,Maassen JA

    更新日期:1994-06-01 00:00:00

  • Insulin-dependent childhood diabetes. Normal viability of cultured fibroblasts.

    abstract::Cultured skin fibroblasts from clinically normal offspring of two parents with non-insulin-dependent diabetes have demonstrated premature senescence as a decreased ability of cells to establish colonies when inoculated at low density (plating efficiency). The present study tested the hypothesis that there is an inhere...


    pub_type: 杂志文章


    authors: Rosenbloom AL,Rosenbloom EK

    更新日期:1978-03-01 00:00:00

  • Induction of the ChREBPβ Isoform Is Essential for Glucose-Stimulated β-Cell Proliferation.

    abstract::Carbohydrate-responsive element-binding protein (ChREBP) is a glucose-sensing transcription factor required for glucose-stimulated proliferation of pancreatic β-cells in rodents and humans. The full-length isoform (ChREBPα) has a low glucose inhibitory domain (LID) that restrains the transactivation domain when glucos...


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    authors: Zhang P,Kumar A,Katz LS,Li L,Paulynice M,Herman MA,Scott DK

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  • Altered monocyte cyclooxygenase response to lipopolysaccharide in type 1 diabetes.

    abstract::Type 1 diabetes is caused by adaptive immune responses, but innate immunity is important because monocytes infiltrate islets. Activated monocytes express cyclooxygenase (COX)-2, promoting prostaglandin-E(2) (PGE(2)) secretion, whereas COX-1 expression is constitutive. We aimed to define monocyte COX expression in type...


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    authors: Beyan H,Goodier MR,Nawroly NS,Hawa MI,Bustin SA,Ogunkolade WB,Londei M,Yousaf N,Leslie RD

    更新日期:2006-12-01 00:00:00

  • Beta-cell failure in diet-induced obese mice stratified according to body weight gain: secretory dysfunction and altered islet lipid metabolism without steatosis or reduced beta-cell mass.

    abstract:OBJECTIVE:C57Bl/6 mice develop obesity and mild hyperglycemia when fed a high-fat diet (HFD). Although diet-induced obesity (DIO) is a widely studied model of type 2 diabetes, little is known about beta-cell failure in these mice. RESEARCH DESIGN AND METHODS:DIO mice were separated in two groups according to body weig...


    pub_type: 杂志文章


    authors: Peyot ML,Pepin E,Lamontagne J,Latour MG,Zarrouki B,Lussier R,Pineda M,Jetton TL,Madiraju SR,Joly E,Prentki M

    更新日期:2010-09-01 00:00:00

  • Ameliorating Methylglyoxal-Induced Progenitor Cell Dysfunction for Tissue Repair in Diabetes.

    abstract::Patient-derived progenitor cell (PC) dysfunction is severely impaired in diabetes, but the molecular triggers that contribute to mechanisms of PC dysfunction are not fully understood. Methylglyoxal (MGO) is one of the highly reactive dicarbonyl species formed during hyperglycemia. We hypothesized that the MGO scavenge...


    pub_type: 杂志文章


    authors: Li H,O'Meara M,Zhang X,Zhang K,Seyoum B,Yi Z,Kaufman RJ,Monks TJ,Wang JM

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  • Skeletal muscle lipid accumulation in type 2 diabetes may involve the liver X receptor pathway.

    abstract::Liver X receptors (LXRs) are important regulators of cholesterol and lipid metabolism and are also involved in glucose metabolism. However, the functional role of LXRs in human skeletal muscle is at present unknown. This study demonstrates that chronic ligand activation of LXRs by a synthetic LXR agonist increases the...


    pub_type: 杂志文章


    authors: Kase ET,Wensaas AJ,Aas V,Højlund K,Levin K,Thoresen GH,Beck-Nielsen H,Rustan AC,Gaster M

    更新日期:2005-04-01 00:00:00

  • Exposure to elevated D-glucose concentrations modulates vascular endothelial cell vasodilatory response.

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    pub_type: 杂志文章


    authors: Graier WF,Wascher TC,Lackner L,Toplak H,Krejs GJ,Kukovetz WR

    更新日期:1993-10-01 00:00:00

  • Sphingosine kinase activity and sphingosine-1 phosphate production in rat pancreatic islets and INS-1 cells: response to cytokines.

    abstract::Sphingosine-1 phosphate (S1P) is a bioactive sphingolipid with the potential to mobilize Ca2+, to inhibit apoptosis, and to promote mitogenesis. Sphingosine kinase (SPHK) and S1P were characterized in INS-1 insulinoma cells and isolated rat islets of Langerhans. SPHK activity increased in INS-1 cell homogenates treate...


    pub_type: 杂志文章


    authors: Mastrandrea LD,Sessanna SM,Laychock SG

    更新日期:2005-05-01 00:00:00

  • Effects of high glucose concentrations and epalrestat on sorbitol and myo-inositol metabolism in cultured rabbit aortic smooth muscle cells.

    abstract::To clarify the relationship between abnormality of sorbitol and/or myo-inositol metabolism caused by hyperglycemia and diabetic macroangiopathy, we investigated the effects of high glucose concentrations and epalrestat, an aldose reductase inhibitor, on the metabolism of sorbitol and myo-inositol in cultured rabbit ao...


    pub_type: 杂志文章


    authors: Sakakibara F,Hotta N,Koh N,Sakamoto N

    更新日期:1993-11-01 00:00:00

  • Malonyl CoenzymeA decarboxylase regulates lipid and glucose metabolism in human skeletal muscle.

    abstract:OBJECTIVE:Malonyl coenzyme A (CoA) decarboxylase (MCD) is a key enzyme responsible for malonyl-CoA turnover and functions in the control of the balance between lipid and glucose metabolism. We utilized RNA interference (siRNA)-based gene silencing to determine the direct role of MCD on metabolic responses in primary hu...


    pub_type: 杂志文章


    authors: Bouzakri K,Austin R,Rune A,Lassman ME,Garcia-Roves PM,Berger JP,Krook A,Chibalin AV,Zhang BB,Zierath JR

    更新日期:2008-06-01 00:00:00

  • The effect of glucose on proteoglycans produced by cultured mesangial cells.

    abstract::Altered proteoglycan metabolism may play a role in the development of diabetic glomerulopathy. This study was conducted to examine the effects of glucose on the production and physical characteristics of proteoglycans generated by rat mesangial cells in culture. Rat mesangial cells were exposed to elevated glucose med...


    pub_type: 杂志文章


    authors: Silbiger S,Schlondorff D,Crowley S,Rosenberg L,Choi H,Hatcher V,Gordon P

    更新日期:1993-12-01 00:00:00

  • Platelet survival in patients with diabetes mellitus.

    abstract::Platelet survival by 51chromium labeling was determined in six normal control subjects and in twelve patients with diabetes mellitus, before and after improved glucose control (mean HbA1c 10.5 +/- 2.2% and 7.1 +/- 1.8%, respectively). Mean platelet survival was 9.47 +/- 0.85 days for the normal subjects and 9.04 +/- 1...


    pub_type: 杂志文章


    authors: Jones RL,Paradise C,Peterson CM

    更新日期:1981-06-01 00:00:00

  • The role of enteroviral infections in the development of IDDM: limitations of current approaches.

    abstract::Enteroviruses have been examined for their possible role in the etiology of IDDM for nearly 40 years, yet the evidence remains inconclusive. The mechanism of acute cytolytic infection of beta-cells, proposed by earlier studies, appears to be incompatible with the long preclinical period of autoimmunity preceding IDDM....


    pub_type: 杂志文章,评审


    authors: Graves PM,Norris JM,Pallansch MA,Gerling IC,Rewers M

    更新日期:1997-02-01 00:00:00

  • Rosiglitazone (BRL 49653) enhances insulin secretory response via phosphatidylinositol 3-kinase pathway.

    abstract::To elucidate the direct effect of rosiglitazone (RSG), a new thiazolidinedione antihyperglycemic agent, on pancreatic insulin secretion, an in situ investigation by rat pancreatic perfusion was performed. At a basal glucose concentration of 6 mmol/l, RSG (0.045-4.5 micromol/l) stimulated insulin release in a dose-depe...


    pub_type: 杂志文章


    authors: Yang C,Chang TJ,Chang JC,Liu MW,Tai TY,Hsu WH,Chuang LM

    更新日期:2001-11-01 00:00:00

  • Excitatory GABAergic Action and Increased Vasopressin Synthesis in Hypothalamic Magnocellular Neurosecretory Cells Underlie the High Plasma Level of Vasopressin in Diabetic Rats.

    abstract::Diabetes mellitus (DM) is associated with increased plasma levels of arginine-vasopressin (AVP), which may aggravate hyperglycemia and nephropathy. However, the mechanisms by which DM may cause the increased AVP levels are not known. Electrophysiological recordings in supraoptic nucleus (SON) slices from streptozotoci...


    pub_type: 杂志文章


    authors: Kim YB,Kim WB,Jung WW,Jin X,Kim YS,Kim B,Han HC,Block GD,Colwell CS,Kim YI

    更新日期:2018-03-01 00:00:00

  • Effect of coxsackievirus B4 infection in mice on expression of 64,000-Mr autoantigen and glucose sensitivity of islets before development of hyperglycemia.

    abstract::Diabetogenic strains of Coxsackievirus B4 (CB4) produce a diabetes syndrome in susceptible mice that resembles insulin-dependent diabetes mellitus. To assess the possible role of autoimmunity, the expression of a 64,000-Mr islet antigen in SJL/J and CD1 mice infected with a diabetogenic strain of CB4 was monitored in ...


    pub_type: 杂志文章


    authors: Gerling I,Nejman C,Chatterjee NK

    更新日期:1988-10-01 00:00:00

  • Evidence for a circadian rhythm of insulin sensitivity in patients with NIDDM caused by cyclic changes in hepatic glucose production.

    abstract::Diurnal variation in insulin sensitivity in patients with NIDDM has long been suspected but has been difficult to document mainly because of the interdependence of changes in glucose and insulin. Stable serum insulin levels during hyperglycemic clamping in patients with NIDDM in the present study provided the opportun...


    pub_type: 杂志文章


    authors: Boden G,Chen X,Urbain JL

    更新日期:1996-08-01 00:00:00

  • Immunoreactivity of human insulin of recombinant DNA origin.

    abstract::To evaluate possible advantages of human insulin of recombinant DNA origin (HI) in the treatment of diabetic patients, we compared cellular and humoral immunoreactivities of HI and porcine insulin (PI). Anti-insulin IgE bound equal amounts of 125I-HI and 125I-PI. There was no difference between HI- and PI-stimulated l...


    pub_type: 杂志文章


    authors: Kumar D,Alexander CM,Zeidler A,Rhodes JJ,Boarman CC,Hoopes MT

    更新日期:1983-06-01 00:00:00

  • DLL1- and DLL4-Mediated Notch Signaling Is Essential for Adult Pancreatic Islet Homeostasis.

    abstract::Genes of the Notch signaling pathway are expressed in different cell types and organs at different time points during embryonic development and adulthood. The Notch ligand Delta-like 1 (DLL1) controls the decision between endocrine and exocrine fates of multipotent progenitors in the developing pancreas, and loss of D...


    pub_type: 杂志文章


    authors: Rubey M,Chhabra NF,Gradinger D,Sanz-Moreno A,Lickert H,Przemeck GKH,Hrabě de Angelis M

    更新日期:2020-05-01 00:00:00

  • Women with mitochondrial haplogroup N9a are protected against metabolic syndrome.

    abstract::To identify mitochondrial haplogroups that confer resistance against or susceptibility to metabolic syndrome, we performed a large-scale association study on 1,337 unrelated Japanese individuals, including 871 subjects with metabolic syndrome and 466 control subjects. Metabolic syndrome was diagnosed according to modi...


    pub_type: 杂志文章


    authors: Tanaka M,Fuku N,Nishigaki Y,Matsuo H,Segawa T,Watanabe S,Kato K,Yokoi K,Ito M,Nozawa Y,Yamada Y

    更新日期:2007-02-01 00:00:00

  • Report of the American Diabetes Association's Task Force on standardization of the insulin assay.

    abstract::Recent large-scale epidemiological studies demonstrate that blood concentrations of immunoreactive insulin predict the development of NIDDM and IDDM and are associated with the risk of several degenerative diseases, such as coronary and peripheral vessel atherosclerosis, hypertension, and dyslipidemia. The reliability...


    pub_type: 杂志文章


    authors: Robbins DC,Andersen L,Bowsher R,Chance R,Dinesen B,Frank B,Gingerich R,Goldstein D,Widemeyer HM,Haffner S,Hales CN,Jarett L,Polonsky K,Porte D,Skyler J,Webb G,Gallagher K

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  • Mitogen-activated protein kinase p38 mediates reduced nerve conduction velocity in experimental diabetic neuropathy: interactions with aldose reductase.

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    pub_type: 杂志文章


    authors: Price SA,Agthong S,Middlemas AB,Tomlinson DR

    更新日期:2004-07-01 00:00:00

  • Otopetrin 1 protects mice from obesity-associated metabolic dysfunction through attenuating adipose tissue inflammation.

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    pub_type: 杂志文章


    authors: Wang GX,Cho KW,Uhm M,Hu CR,Li S,Cozacov Z,Xu AE,Cheng JX,Saltiel AR,Lumeng CN,Lin JD

    更新日期:2014-04-01 00:00:00

  • Reactivity to human islets and fetal pig proislets by peripheral blood mononuclear cells from subjects with preclinical and clinical insulin-dependent diabetes.

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    pub_type: 杂志文章


    authors: Harrison LC,De Aizpurua H,Loudovaris T,Campbell IL,Cebon JS,Tait BD,Colman PG

    更新日期:1991-09-01 00:00:00

  • Higher proinsulin and specific insulin are both associated with a parental history of diabetes in nondiabetic Mexican-American subjects.

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    pub_type: 杂志文章


    authors: Haffner SM,Stern MP,Miettinen H,Gingerich R,Bowsher RR

    更新日期:1995-10-01 00:00:00

  • Hepatocyte nuclear factor-4alpha P2 promoter haplotypes are associated with type 2 diabetes in the Japanese population.

    abstract::Hepatocyte nuclear factor (HNF)-4alpha is a transcription factor known as a key molecule in the development and functions of the beta-cells. In a previously performed genome-wide scan of Japanese type 2 diabetic sibpairs, we observed linkage of type 2 diabetes to chromosome 20q12-q13, a region in which the HNF4A gene ...


    pub_type: 杂志文章


    authors: Hara K,Horikoshi M,Kitazato H,Ito C,Noda M,Ohashi J,Froguel P,Tokunaga K,Tobe K,Nagai R,Kadowaki T

    更新日期:2006-05-01 00:00:00

  • Muscle glycogen synthesis and disposition of infused glucose in humans with reduced rates of insulin-mediated carbohydrate storage.

    abstract::Six men with a low rate of insulin-stimulated, non-oxidative carbohydrate disposal (storage) and six with a high storage rate were recruited for study of the fate of insulin-stimulated glucose uptake. [3-3H]glucose was infused before and during a 4-h hyperinsulinemic euglycemic clamp procedure in a dosage regimen desi...


    pub_type: 杂志文章


    authors: Young AA,Bogardus C,Wolfe-Lopez D,Mott DM

    更新日期:1988-03-01 00:00:00

  • Adiponectin Deficiency Impairs Maternal Metabolic Adaptation to Pregnancy in Mice.

    abstract::Hypoadiponectinemia has been widely observed in patients with gestational diabetes mellitus (GDM). To investigate the causal role of hypoadiponectinemia in GDM, adiponectin gene knockout (Adipoq-/- ) and wild-type (WT) mice were crossed to produce pregnant mouse models with or without adiponectin deficiency. Adenovira...


    pub_type: 杂志文章


    authors: Qiao L,Wattez JS,Lee S,Nguyen A,Schaack J,Hay WW Jr,Shao J

    更新日期:2017-05-01 00:00:00

  • β-Cell-specific protein kinase A activation enhances the efficiency of glucose control by increasing acute-phase insulin secretion.

    abstract::Acute insulin secretion determines the efficiency of glucose clearance. Moreover, impaired acute insulin release is characteristic of reduced glucose control in the prediabetic state. Incretin hormones, which increase β-cell cAMP, restore acute-phase insulin secretion and improve glucose control. To determine the phys...


    pub_type: 杂志文章


    authors: Kaihara KA,Dickson LM,Jacobson DA,Tamarina N,Roe MW,Philipson LH,Wicksteed B

    更新日期:2013-05-01 00:00:00