Time Dependence of Insulin Action in Muscle and Adipose Tissue in the Rat In Vivo: An Increasing Response in Adipose Tissue with Time

James, David E.; Burleigh, K. M.; Kraegen, Edward W.

doi:10.2337/diab.34.10.1049

Cited by 46 publications

(20 citation statements)

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“…These results suggest that whole-body glucose tolerance in mice fed KD is impaired by the impairment of insulin signaling in white adipose tissue. However, James et al reported that white adipose tissue accounts for less than 10% of whole-body glucose uptake in rat fed normal chow [22]. Therefore it cannot be assumed that the impairment of glucose uptake in white adipose tissue is solely responsible for whole-body glucose intorelance in mice fed KD.…”

Section: Discussionmentioning

confidence: 99%

Fgf21 Impairs Adipocyte Insulin Sensitivity in Mice Fed a Low-Carbohydrate, High-Fat Ketogenic Diet

et al. 2013

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BackgroundA low-carbohydrate, high-fat ketogenic diet (KD) induces hepatic ketogenesis and is believed to affect energy metabolism in mice. As hepatic Fgf21 expression was markedly induced in mice fed KD, we examined the effects of KD feeding on metabolism and the roles of Fgf21 in metabolism in mice fed KD using Fgf21 knockout mice.Methodology/Principal FindingsWe examined C57BL/6 mice fed KD for 6 or 14 days. Blood β-hydroxybutyrate levels were greatly increased at 6 days, indicating that hepatic ketogenesis was induced effectively by KD feeding for 6 days. KD feeding for 6 and 14 days impaired glucose tolerance and insulin sensitivity, although it did not affect body weight, blood NEFA, and triglyceride levels. Hepatic Fgf21 expression and blood Fgf21 levels were markedly increased in mice fed KD for 6 days. Blood β-hydroxybutyrate levels in the knockout mice fed KD for 6 days were comparable to those in wild-type mice fed KD, indicating that Fgf21 is not required for ketogenesis. However, the impaired glucose tolerance and insulin sensitivity caused by KD feeding were improved in the knockout mice. Insulin-stimulated Akt phosphorylation was significantly decreased in the white adipose tissue in wild-type mice fed KD compared with those fed normal chow, but not in the muscle and liver. Its phosphorylation in the white adipose tissue was significantly increased in the knockout mice fed KD compared with wild-type mice fed KD. In contrast, hepatic gluconeogenic gene expression in Fgf21 knockout mice fed KD was comparable to those in the wild-type mice fed KD.Conclusions/SignificanceThe present findings indicate that KD feeding impairs insulin sensitivity in mice due to insulin resistance in white adipose tissue. In addition, our findings indicate that Fgf21 induced to express by KD is a negative regulator of adipocyte insulin sensitivity in adaptation to a low-carbohydrate malnutritional state.

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Section: Discussionmentioning

confidence: 99%

Fgf21 Impairs Adipocyte Insulin Sensitivity in Mice Fed a Low-Carbohydrate, High-Fat Ketogenic Diet

et al. 2013

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“…Depletion of GLUT4 selectively in the adipose tissue does not result in decreased adipose mass or adipocyte size (41). In addition, WAT accounts for <10% of whole‐body glucose uptake (42). Thus, decreased adipocyte FA uptake may represent a major contributor to the limited adiposity in CD36‐null mice.…”

Section: Discussionmentioning

confidence: 99%

CD36 level and trafficking are determinants of lipolysis in adipocytes

et al. 2012

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CD36 has been linked to the etiology of insulin resistance and inflammation. We explored its function in regulating adipose tissue lipolysis, which influences fat accumulation by liver and muscle and overall metabolism. Knockdown of CD36 in differentiated 3T3-L1 adipocytes decreased lipolysis in response to 10 μM of the β-adrenergic agonist isoproterenol (by 42%), 10 μM of the adenyl cyclase activator forskolin (by 32%), and 500 μM of the phosphodiesterase (PDE) inhibitor isobutylmethylxanthine (by 33%). All three treatments in the knockdown adipocytes were associated with significant decreases of cAMP levels and of the hormone-sensitive lipase (HSL) and perilipin phosphorylation. An important role for PDE was supported by the lack of inhibition of the lipolysis induced by the poorly hydrolyzable dibutyryl cAMP analog. An additional contributory mechanism was diminished activation of the Src-ERK1/2 pathway. Regulation of lipolysis and lipolytic signaling by CD36 was reproduced with adipose tissue from CD36(-/-) mice. The importance of surface CD36 in this regulation was suggested by the finding that the plasma membrane-impermeable CD36 inhibitor sulfo-N-succinimidyl oleate (20 μM) decreased lipolysis. Interestingly, isoproterenol induced CD36 internalization, and this process was blocked by HSL inhibition, suggesting feedback regulation of adipocyte lipolysis via CD36 trafficking.

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“…Although white adipose tissue accounts for less than 20% of whole-body glucose uptake (285), adipose-specific GLUT4 knockout mice are insulin resistant and glucose intolerant (431). As expected, insulin-stimulated (GLUT4-dependent) 2-deoxy-D-glucose uptake into white and brown adipose in vivo is markedly reduced.…”

Section: Kinetics Of Glucose Distribution and Metabolismmentioning

confidence: 99%

Role of Monosaccharide Transport Proteins in Carbohydrate Assimilation, Distribution, Metabolism, and Homeostasis

Cura

Carruthers

2012

Comprehensive Physiology

134

117

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The facilitated diffusion of glucose, galactose, fructose, urate, myoinositol, and dehydroascorbic acid in mammals is catalyzed by a family of 14 monosaccharide transport proteins called GLUTs. These transporters may be divided into three classes according to sequence similarity and function/substrate specificity. GLUT1 appears to be highly expressed in glycolytically active cells and has been coopted in vitamin C auxotrophs to maintain the redox state of the blood through transport of dehydroascorbate. Several GLUTs are definitive glucose/galactose transporters, GLUT2 and GLUT5 are physiologically important fructose transporters, GLUT9 appears to be a urate transporter while GLUT13 is a proton/myoinositol cotransporter. The physiologic substrates of some GLUTs remain to be established. The GLUTs are expressed in a tissue specific manner where affinity, specificity, and capacity for substrate transport are paramount for tissue function. Although great strides have been made in characterizing GLUT‐catalyzed monosaccharide transport and mapping GLUT membrane topography and determinants of substrate specificity, a unifying model for GLUT structure and function remains elusive. The GLUTs play a major role in carbohydrate homeostasis and the redistribution of sugar‐derived carbons among the various organ systems. This is accomplished through a multiplicity of GLUT‐dependent glucose sensing and effector mechanisms that regulate monosaccharide ingestion, absorption, distribution, cellular transport and metabolism, and recovery/retention. Glucose transport and metabolism have coevolved in mammals to support cerebral glucose utilization. © 2012 American Physiological Society. Compr Physiol 2:863‐914, 2012.

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Time Dependence of Insulin Action in Muscle and Adipose Tissue in the Rat In Vivo: An Increasing Response in Adipose Tissue with Time

Cited by 46 publications

References 0 publications

Fgf21 Impairs Adipocyte Insulin Sensitivity in Mice Fed a Low-Carbohydrate, High-Fat Ketogenic Diet

Fgf21 Impairs Adipocyte Insulin Sensitivity in Mice Fed a Low-Carbohydrate, High-Fat Ketogenic Diet

CD36 level and trafficking are determinants of lipolysis in adipocytes

Role of Monosaccharide Transport Proteins in Carbohydrate Assimilation, Distribution, Metabolism, and Homeostasis

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