胰岛素增强缺血心肌葡萄糖转运子1基因表达的实验研究

目的:探讨胰岛素刺激低血流缺血心肌增加葡萄糖摄取的机制。方法:采用Northern法分析缺血心肌葡萄糖转运子-1(GLUT1)mRNA和免疫法分析心肌葡萄糖转运子1(GLUT1)多肽水平。结果:胰岛素使局部低血流缺血心肌GLUT1 mRNA和GLUT1多肽表达明显增加。同时伴随缺血心肌葡萄糖摄取明显增多。结论:胰岛素能增强缺血心肌GLUT1 mRNA和GLUT1多肽表达,使GLUT1数增加,进而促进心肌葡萄糖摄取增多,胰岛素增强低血流缺血刺激的心肌GLUT1表达。     

Expression of glucose transporter isoforms and the insulin receptor during hamster preimplantation embryo development

During preimplantation development, embryos of many species are known to express up to five isoforms of the facilitative glucose transporter proteins (GLUT). Development of hamster blastocysts is inhibited by glucose. We therefore investigated GLUT isoform and insulin receptor (IR) expression in hamster preimplantation embryos cultured in glucose-free medium from the 8-cell stage onwards. We show that GLUT1, 3 and 8 mRNA are constitutively expressed from the 8-cell to the blastocyst stage. The IR is expressed from the morula stage onwards. Messenger RNA of the insulin-responsive GLUT4 was not detected at any stage. GLUT1 and 3 were localised by immunocytochemistry. GLUT1 was expressed in both embryoblast and trophoblast, in the latter, mainly in basal and lateral membranes directed towards the blastocoel and embryoblast. GLUT3 was exclusively localised in the apical membrane of trophoblast cells. We show that hamster preimplantation embryos express several GLUT isoforms thus closely resembling embryos of other mammalian species. Despite endogenous IR expression, the insulin-sensitive isoform GLUT4 was not expressed, indicating that the insulin-mediated glucose uptake known from classical insulin target cells may not be relevant for hamster blastocysts.     

Passive stretching produces Akt- and MAPK-dependent augmentations of GLUT4 translocation and glucose uptake in skeletal muscles of mice

Muscle contraction is accompanied by passive stretching or deformation of cells and tissues. The present study aims to clarify whether or not acute passive stretching evokes glucose transporter 4 (GLUT4) translocation and glucose uptake in skeletal muscles of mice. Passive stretching mainly induced GLUT4 translocation from an intracellular membrane-rich fraction (PF5) to a plasma membrane-rich fraction (F2) and accelerated glucose uptake in hindlimb muscles; whereas electrical stimulation, which mimics physical exercise in vivo, and insulin, each induced GLUT4 translocation from an intracellular membrane-rich fraction (PF5) to a fraction rich in plasma membrane (F2), and to one rich in transverse tubules (PF3), along with subsequent glucose uptake. Mechanical stretching increased phosphorylation of Akt and p38 mitogen-activated protein kinase (p38 MAPK), but it had no apparent effect on the activity of AMP-activated protein kinase (AMPK). Electrical stimulation augmented the activity of not only AMPK but also phosphorylation of Akt and p38 MAPK. Our results suggest that passive stretching produces translocation of GLUT4 mainly from the fraction rich in intracellular membrane to that rich in plasma membrane, and that the glucose uptake could be Akt- and p38 MAPK-dependent, but AMPK-independent manners.     

葡萄糖对成骨细胞体外发育和葡萄糖载体1表达的影响

目的 探讨葡萄糖对成骨细胞体外发育和葡萄糖载体1表达的影响.方法 组织块培养法培养新生大鼠颅骨成骨细胞,再将成骨细胞分两组培养:正常浓度组(含5.5 mmol/L葡萄糖培养液)和高浓度组(含25.5 mmol/L葡萄糖培养液).四甲基偶氮唑蓝(MTT)法检测细胞增殖,茜素红S钙染色法检测骨结节形成,反转录(RT)PCR和Western免疫印迹检测成骨细胞葡萄糖载体1 mRNA和蛋白表达情况.结果 与正常浓度葡萄糖相比,高浓度葡萄糖在第3、4、5天显著促进成骨细胞的增殖[ (0.390 0±0.002 4)比(0.320 0±0.012 7),( 0.540 0±0.009 4)比(0.440 0±0.004 6),( 0.720 0±0.001 3)比(0.600 0±0.006 1),均P＜0.05],但抑制其矿化和骨结节形成.正常浓度组形成肉眼可见的钙化结节要早于高浓度组(第9天比第14天).实验最后ld(第32天),高浓度组的骨结节数明显少于正常浓度组(P＜0.05).与正常浓度组相比,高浓度葡萄糖使成骨细胞葡萄糖载体l mRNA和蛋白的表达增加.结论 高浓度葡萄糖刺激成骨细胞增殖但抑制细胞矿化可能直接引起成骨细胞骨形成障碍.高浓度葡萄糖引起成骨细胞葡萄糖载体1表达的改变可能在骨质量变化过程中起重要作用.     

A gene knockout approach in mice to identify glucose sensors controlling glucose homeostasis

A key aspect of glucose homeostasis is the constant monitoring of blood glucose concentrations by specific glucose sensing units. These sensors, via stimulation of hormone secretion and activation of the autonomic nervous system (ANS), regulate tissue glucose uptake, utilization or production. The best described glucose detection system is that of the pancreatic beta-cells which controls insulin secretion. Secretion of other hormones, in particular glucagon, and activation of the ANS, are regulated by glucose through sensing mechanisms which are much less well characterized. Here I review some of the studies we have performed over the recent years on a mouse model of impaired glucose sensing generated by inactivation of the gene for the glucose transporter GLUT2. This transporter catalyzes glucose uptake by pancreatic beta-cells, the first step in the signaling cascade leading to glucose-stimulated insulin secretion. Inactivation of its gene leads to a loss of glucose sensing and impaired insulin secretion. Transgenic reexpression of the transporter in GLUT2/beta-cells restores their normal secretory function and rescues the mice from early death. As GLUT2 is also expressed in other tissues, these mice were then studied for the presence of other physiological defects due to absence of this transporter. These studies led to the identification of extra-pancreatic, GLUT2-dependent, glucose sensors controlling glucagon secretion and glucose utilization by peripheral tissues, in part through a control of the autonomic nervous system.     

Dissociation of the effects of training on oxidative metabolism,glucose utilisation and GLUT4 levels in skeletal muscle of streptozotocin-diabetic rats

The effects of long-term, moderate physical exercise on in vivo glucose uptake, levels of two glucose transporter proteins (GLUT1 and GLUT4) and activities of various key enzymes of energy metabolism were measured in skeletal muscle from streptozotocin-diabetic rats. Diabetes (12–16 weeks) reduced the in vivo glucose uptake (glucose metabolic index, GMI) in muscle containing mainly type I fibres by 55% but had no effect in muscles containing mainly type IIa and IIb fibres. GMI was increased in the diabetic white skeletal muscle (mainly type IIb fibres) by more than 120%. In contrast to the complex changes in GMI, GLUT4 levels were reduced in all types of skeletal muscle from diabetic rats with no change in GLUT1 levels. Exercise training had no effects on GMI or the glucose transporter levels. Streptozotocin induced diabetes significantly reduced the oxidative capacity of skeletal muscle assayed as the activities of citrate synthase, succinate dehydrogenase and cytochrome c oxidase. Training increased the activities of oxidative enzymes, with this increase being more prominent in the diabetic animals. The present data indicate that long-term streptozotocin-induced diabetes decreases oxidative metabolic capacity and GLUT4 protein levels in skeletal muscle, but that the changes of glucose transport largely depend on the fibre type composition. Moderate training fully reverses the effect of insulinopenia and hyperglycaemia on muscle oxidative metabolism. In contrast to the previous suggestions, the expression of GLUT4 is not correlated with the capacity of oxidative metabolism in skeletal muscle of streptozotocin-diabetic rats.     

Cellular location of insulin-triggered signals and implications for glucose uptake

Insulin stimulation of glucose uptake into muscle and fat cells requires movement of GLUT4-containing vesicles from intracellular compartments to the plasma membrane. Accordingly, insulin-derived signals must arrive at and be recognized by the appropriate intracellular GLUT4 pools. We describe the insulin signals participating in GLUT4 translocation, and review evidence that they are recruited to intracellular membranes in conjunction with cytoskeletal elements. Such segregation may facilitate the encounter between signals and target vesicles. In most animal and cellular models of insulin resistance, insulin-stimulated GLUT4 translocation to the plasma membrane is reduced. Insulin resistance caused by oxidative stress does not affect early insulin signals, rather their intracellular localization is altered. In this and several other insulin-resistant states, insulin-induced actin remodelling is concomitantly diminished. We summarize evidence suggesting that spatial localization of signals is critical for efficient insulin action, and that the cytoskeleton may act as a scaffold to promote efficient translocation of GLUT4 to the cell surface.     

Protein kinase C-ζ regulation of GLUT4 translocation through actin remodeling in CHO cells

Actin remodeling plays a crucial role in insulin-induced translocation of glucose transporter 4 (GLUT4) from the cytoplasm to the plasma membrane and subsequent glucose transport. Protein kinase C (PKC) zeta has been implicated in this translocation process, although the exact mechanism remains unknown. In this study, we investigated the effect of PKCzeta on actin cytoskeleton and translocation of GLUT4 in CHO-K1 cells expressing myc-tagged GLUT4. Insulin stimulated the phosphorylation of PKCzeta at Thr410 with no apparent effect on its protein expression. Moreover, insulin promoted colocalization of PKCzeta and actin that could be abolished by Latrunculin B. The overexpression of PKCzeta mimicked the insulin-induced change in actin cytoskeleton and translocation of GLUT4. These effects were also completely abrogated by Latrunculin B treatment. Using cell-permeable pseudosubstrate (PS) inhibitor of PKCzeta, the response to insulin could be alleviated. Our results strongly suggest that PKCzeta mediates the stimulatory effect of insulin on GLUT4 translocation through its interaction with actin cytoskeleton.     

Glucose transporter plasticity during memory processing

Various types of learning, including operant conditioning, induce an increase in cellular activation concomitant with an increase in local cerebral glucose utilization (LCGU). This increase is mediated by increased cerebral blood flow or changes in brain capillary density and diameter. Because glucose transporters are ultimately responsible for glucose uptake, we examined their plastic expression in response to cellular activation. In vitro and in vivo studies have demonstrated that cerebral glucose transporter 1 (GLUT1) expression consistently parallels changes in LCGU. The present study is the first to investigate the effect of memory processing on glucose transporters expression. Changes in GLUT expression produced by training in an operant conditioning task were measured in the brain of CD1 mice. Using semi-quantitative immunohistochemistry, Western blot and real time RT-PCR the cerebral GLUT1 and GLUT3 expression was quantified immediately, 220 min and 24 h following training. Relative to sham-trained and naive controls, operant conditioning training induced an immediate increase in GLUT1 immunoreactivity level in the hippocampus CA1 pyramidal cells as well as in the sensorimotor cortex. At longer post-learning delays, GLUT1 immunoreactivity decreased in the sensorimotor cortex and putamen. Parallel to the changes in protein levels, hippocampus GLUT1 mRNA level also increased immediately following learning. No effect of learning was found on hippocampal GLUT3 protein or mRNA expression. Measures of changes in glucose transporters expression present a link between cellular activation and glucose metabolism. The learning-induced localized increases in GLUT1 protein as well as mRNA levels observed in the present study confirm the previous findings that GLUT1 expression is plastic and respond to changes in cellular metabolic demands.     

Opposite Effects of Quercetin, Luteolin, and Epigallocatechin Gallate on Insulin Sensitivity Under Normal and Inflammatory Conditions in Mice

Flavonoids are polyphenolic compounds ubiquitous in plants. Quercetin, luteolin, and epigallocatechin gallate (EGCG) are flavonoids with a number of biochemical and cellular actions relevant to glucose homeostasis, but their regulation of insulin action is still uncertain. This study aims to evaluate the regulation of insulin action by quercetin, luteolin, and EGCG under normal and inflammatory conditions in mice. Oral administration of quercetin, luteolin, and EGCG impaired glucose tolerance and blunted the effect of insulin to low blood glucose. Luteolin and EGCG, but not quercetin, inhibited glucose load-induced insulin receptor substrate-1(IRS-1) tyrosine and Akt phosphorylation in adipose tissue. Meanwhile, insulin-stimulated glucose uptake was also inhibited by these flavonoids. We induced insulin resistance in mice by treatment with activated macrophages-derived conditioned medium (Mac-CM) and observed that quercetin, luteolin, and EGCG reversed glucose intolerance with improving insulin sensitivity. Quercetin, luteolin, and EGCG inhibited inflammation-evoked IKKβ activation and IRS-1 serine phosphorylation in adipose tissue, and thereby effectively restored glucose load-stimulated IRS-1 tyrosine and Akt phosphorylation, leading to an increase in insulin-mediated glucose uptake in adipocytes. The aforementioned results showed opposite effects of quercetin, luteolin, and EGCG on insulin sensitivity in mice. The different modulation of IRS-1 function by phosphorylating modification under normal and inflammatory conditions should be a key controlling for their action in regulation of insulin sensitivity.     

Hyperosmotic shock induces both activation and translocation of glucose transporters in mammalian cells

The effect of osmotic stress on sugar transport was investigated in Clone 9 epithelial cells, which express the glucose uniporter GLUT1, and in 3T3-L1 adipocytes, which express both GLUT1 and GLUT4. An acute hyperosmotic shock increased the uptake of sugars in both cell types. In Clone 9 cells, this was followed by a regulatory volume increase (RVI) response. Stimulation of transport was rapid and reversible, with half-lives (t 1/2) for stimulation of 2-deoxy-D-glucose uptake of 5.6 +/- 0.9 (n=6) and 22.7 +/- 1.5 (n=4) min for Clone 9 cells and adipocytes respectively. The effect was dose dependent, reaching a maximum at 1.1 osM of 2.9 +/- 0.1-fold (n=3) for Clone 9 cells and 8.2 +/- 0.8-fold (n=3) for adipocytes. In the latter, this stimulation correlated with translocation of the glucose transporter isoform GLUT4 to the cell surface and was not significantly different from that elicited by 160 nM insulin (7.6 +/- 1.2-fold, n=3). The effect of osmotic shock was not, however, influenced by inhibitors of either phosphoinositide 3-kinase (PI 3-kinase) (wortmannin, 250 nM) or of p38 mitogen-activated protein kinase (p38 MAP kinase) (SB203580, 20 microM), which reportedly prevent GLUT4 translocation and/or activation by insulin respectively. These inhibitors also had no effect on the stimulation of transport by osmotic shock in Clone 9 cells. However, in contrast to adipocytes, the effect of osmotic shock on glucose transport in Clone 9 cells reflected primarily a change in the intrinsic activity of cell surface transporters and there was only a minor change in their subcellular distribution as assessed by cell immunostaining or no change as assessed by surface biotinylation. These results indicate that the response of cells to osmotic shock can involve changes both in transporter activity and location. The signal transduction pathways involved include neither PI 3-kinase nor the classical, osmotically-activated component, p38 MAP kinase.     

Treadmill exercise training fails to reverse defects in glucose, insulin and muscle GLUT4 content in the db/db mouse model of diabetes

OBJECTIVE: Regular exercise is recommended for the treatment of type 2 diabetes because of the benefits on body weight and glycemic control. The present study was designed to compare the impact of voluntary wheel and forced treadmill running on the metabolic state in the db/db mouse model of type 2 diabetes. Our hypothesis is that voluntary exercise training reduces body weight, blood glucose and insulin levels and restores GLUT4 levels in skeletal muscle, whereas forced exercise training produces a greater effect. STUDY DESIGN: Male diabetic db/db mice were assigned to sedentary (DS), voluntary wheel running (DV), and forced treadmill running (DT) groups for 12 weeks. Nondiabetic heterozygote littermates served as control (CN). RESULTS: Over the 12-week period, DV and DT mice ran a total of 4.24+/-0.18km and 11.8km, respectively. At week 12, fasting plasma glucose was decreased in DV mice compared to DS mice and occurred in the absence weight loss. In DT mice, body weight and fasting plasma glucose were not improved with exercise when compared to DS mice and were actually higher compared to DV mice. After training, fasting plasma insulin was increased in DS mice compared to CN mice and training failed to normalize plasma insulin levels. Gastrocnemius GLUT4 content was reduced in DS mice compared to CN mice and training had no effect in preventing this depression from occurring. CONCLUSION: The results of this study indicate that while voluntary exercise improved only blood glucose, forced treadmill exercise training failed to restore body weight, blood glucose and insulin, and muscle GLUT4 content.     

GLUT3阳性神经细胞在大鼠脑中的分布及其与脑内葡萄糖监控系统的关系

本文利用抗ＧＬＵＴ３ Ｃ－末端部分合成肽的抗血清对大鼠脑中ＧＬＵＴ３ 阳性神经细胞的分布进行了免疫组织化学研究。结果表明,除在大脑皮层的广泛区域和海马ＣＡ 区存在大量的ＧＬＵＴ３ 阳性神经元外,皮层下的某些核团和区域的神经元以及第三脑室腹侧部的ｔａｎｙｃｙｔｅ 也表达丰富的ＧＬＵＴ３ 蛋白。有趣的是,这些核团的大部分参与构成脑内葡萄糖监控系统的神经网络,有些阳性细胞（如下丘脑外侧区,黑质的神经元和ｔａｎｙｃｙｔｅ ）是这一网络中对血液和脑脊液中葡萄糖浓度发生反应的化学敏感细胞。这一新发现提示ＧＬＵＴ３ 可能与血糖浓度的神经调控有关。     

Expression of the insulin-responsive glucose transporter isoform 4 in blastocysts of C57/BL6 mice

Glucose is the most important energy substrate for mammalian blastocysts. In preimplantation embryos glucose uptake is mainly mediated by facilitative glucose transporter molecules (GLUT). Employing RT-PCR in 3.5-day-old mouse blastocysts of strain C57/BL6 we have investigated the expression of the GLUT isoforms 1–4 and 8. We could not only detect GLUT 1, 3 and 8 but, in contrast to earlier studies, also the insulin-responsive isoform 4. GLUT2 was not expressed. The specificity for GLUT4 amplification was verified by sequence analysis. GLUT4 protein was localized by immunohistochemistry with two GLUT4 antibodies. It was found in ICM and trophoblast cells in the cytoplasmic compartment with a strong perinuclear staining. This is the first report on the expression of the insulin-sensitive GLUT4 isoform in mouse preimplantation embryos.Abbreviations GLUT Glucose transporter - ICM Inner cell mass - TE Trophectoderm     

胰岛素促进犬在体心肌细胞葡萄糖转运子4基因表达

目的 探索胰岛素促进心肌细胞葡萄糖摄取增强的机制。方法 采用Northern法分析心肌LGUT4mRNA和免疫法分析心肌GLUT4多肽。结果 胰岛素刺激心肌GLUT4mRNA和GLUT4多肽表达增加1-1.2倍,同时伴随心肌葡萄糖摄取增多。结论 胰岛素能刺激GLUT4mRNA和GLUT4多肽表达,使GLUT4数增加,进而促进心采购员葡萄糖摄取增多,胰岛素刺激心肌细胞GLUT4表达,可能是心肌增加葡萄糖摄取的重要分子学机制之一。     

Facilitated glucose transporters play a crucial role throughout mouse preimplantation embryo development

The role of glucose fluctuates during preimplantation mouse embryo development, indicating that a specific interplay exists between glucose metabolism and uptake. In this study, attempts were made to characterize the role of the Na(+)-coupled active and the facilitated glucose transporters (GLUT) during preimplantation development by using specific glucose analogues and transport inhibitors and by examining the expression of GLUT1. One-cell outbred mouse embryos were cultured in medium M16 (5.5 mmol/l glucose), M16 without glucose (M16-G), M16-G + 2-deoxyglucose, M16-G + 3-O-methylglucose, M16 + phlorizin and M16 + phloretin and development to the blastocyst stage assessed. The absence of glucose, or the presence of 3-O-methylglucose, which is taken up but not metabolized, did not inhibit blastocyst development. 2-Deoxyglucose, which is phosphorylated but not metabolized, inhibited blastocyst development. Culture in M16 supplemented with phlorizin, an inhibitor of Na(+)-coupled active glucose transport did not inhibit blastocyst formation. Phloretin had no effect on the cleavage of two-cell embryos to the four-cell stage, but inhibited the morula/blastocyst transition. Both phloretin and phlorizin inhibited glucose uptake in two-cell embryos. Finally, GLUT1 expression was 10-fold less in blastocysts cultured in M16 compared to in-vivo blastocysts and those cultured in M16-G. The results show that both types of glucose transporters influence preimplantation embryo development and that the embryo has an innate ability to control the uptake of glucose by regulating the expression of GLUT1.     

Caffeine and theophylline block insulin-stimulated glucose uptake and PKB phosphorylation in rat skeletal muscles

Aim: Caffeine and theophylline inhibit phosphatidylinositol 3-kinase (PI3-kinase) activity and insulin-stimulated protein kinase B (PKB) phosphorylation. Insulin-stimulated glucose uptake involves PI3-kinase/PKB, and the aim of the present study was to test the hypothesis that caffeine and theophylline inhibit insulin-stimulated glucose uptake in skeletal muscles. Methods: Rat epitrochlearis muscles and soleus strips were incubated with insulin and different concentrations of caffeine and theophylline for measurement of glucose uptake, force development and PKB phosphorylation. The effect of caffeine was also investigated in muscles stimulated electrically. Results: Caffeine and theophylline completely blocked insulin-stimulated glucose uptake in both soleus and epitrochlearis muscles at 10 mm . Furthermore, insulin-stimulated PKB Ser⁴⁷³ and Thr³⁰⁸ and GSK-3β Ser⁹ phosphorylation were blocked by caffeine and theophylline. Caffeine reduced and theophylline blocked insulin-stimulated glycogen synthase activation. Caffeine stimulates Ca²⁺ release and force development increased rapidly to 10–20% of maximal tetanic contraction. Dantrolene (25 μm ), a well-known inhibitor of Ca²⁺-release, prevented caffeine-induced force development, but caffeine inhibited insulin-stimulated glucose uptake in the presence of dantrolene. Contraction, like insulin, stimulates glucose uptake via translocation of glucose transporter-4 (GLUT4). Caffeine and theophylline reduced contraction-stimulated glucose uptake by about 50%, whereas contraction-stimulated glycogen breakdown was normal. Conclusion: Caffeine and theophylline block insulin-stimulated glucose uptake independently of Ca²⁺ release, and the likely mechanism is via blockade of insulin-stimulated PI3-kinase/PKB activation. Caffeine and theophylline also reduced contraction-stimulated glucose uptake, which occurs independently of PI3-kinase/PKB, and we hypothesize that caffeine and theophylline also inhibit glucose uptake in skeletal muscles via an additional and hitherto unknown molecule involved in GLUT4 translocation.     

Intracellular signals involved in glucose control

Many proteins are involved in glucose control. The first step for glucose uptake is insulin receptor-binding. Stimulation of the insulin receptor results in rapid autophosphorylation and conformational changes in the beta chain and the subsequent phosphorylation of the insulin receptor substrate. This results in the docking of several SH2 domain proteins, including PI 3-kinase and other adapters. The final event is glucose transporter (GLUT) translocation to the cell surface. GLUT is in the cytosol but after insulin stimulation, several proteins are activated either in the GLUT vesicles or in the inner membrane. The role of the cytoskeleton is not well known, but it apparently participates in membrane fusion and vesicle mobilization. After glucose uptake, several hexokines metabolize the glucose to generate energy, convert the glucose in glycogen and store it. Type 2 diabetes is characterized by high glucose levels and insulin resistance. The insulin receptor is diminished on the cell surface membrane, tyrosine phosphorylation is decreased, serine and threonine phosphorylation is augmented. Apparently, the main problem with GLUT protein is in its translocation to the cell surface. At present, we know the role of many proteins involved in glucose control. However, we do not understand the significance of insulin resistance at the molecular level with type 2 diabetes.     

Feeding a polyunsaturated fatty acid diet prevents the age-associated decline in glucose uptake observed in rats fed a saturated diet

The ability of the intestine to adapt to changes in environmental stimuli may be compromised with aging. Young animals fed saturated fatty acids (SFA) versus polyunsaturated fatty acids (PUFA) have an increased intestinal uptake of glucose. The objectives of this study were to determine (1) the effects of age on glucose uptake in rats; (2) the influence of feeding SFA versus PUFA; and (3) the mechanisms of these age- and diet-associated changes. Male Fischer 344 rats aged 1, 9 and 24 months received semi-purified isocaloric diets enriched with either SFA or PUFA. The uptake of 14C-labelled D-glucose was determined in vitro using the intestinal sheet method. Northern blotting, Western blotting and immunohistochemistry were used to determine the effects of age and diet on SGLT1, GLUT2 and Na(+)K(+)-ATPase. The mucosal surface area of the jejunum was reduced in 9 and 24 as compared with 1-month-old rats fed SFA. PUFA delayed this age-associated reduction in surface area. In SFA, the ileal uptake of glucose fell with age when expressed on the basis of intestinal or mucosal weight. Feeding PUFA prevented this decline. Alterations in glucose uptake were not paralleled by the changes in SGLT1, GLUT2 or Na(+)K(+)-ATPase abundance.