Biomedical subjects

U F Machado

Publications and source records attributed to U F Machado.

At least 19 recordsLinked to original sources

PubMed2004

Abnormal subcellular distribution of GLUT4 protein in obese and insulin-treated diabetic female dogs.

The GLUT4 transporter plays a key role in insulin-induced glucose uptake, which is impaired in insulin resistance. The objective of the present study was to investigate the tissue content and the subcellular distribution of GLUT4 protein in 4- to 12-year-old control, obese and insulin-treated diabetic mongrel female dogs (4 animals per group). The parametrial white adipose tissue was sampled and processed to obtain both plasma membrane and microsome subcellular fractions for GLUT4 analysis by Western blotting. There was no significant difference in glycemia and insulinemia between control and obese animals. Diabetic dogs showed hyperglycemia (369.9 +/- 89.9 mg/dl). Compared to control, the plasma membrane GLUT4, reported per g tissue, was reduced by 55% (P < 0.01) in obese dogs, and increased by 30% (P < 0.05) in diabetic dogs, and the microsomal GLUT4 was increased by approximately 45% (P < 0.001) in both obese and diabetic animals. Considering the sum of GLUT4 measured in plasma membrane and microsome as total cellular GLUT4, percent GLUT4 present in plasma membrane was reduced by approximately 65% (P < 0.001) in obese compared to control and diabetic animals. Since insulin stimulates GLUT4 translocation to the plasma membrane, percent GLUT4 in plasma membrane was divided by the insulinemia at the time of tissue removal and was found to be reduced by 75% (P < 0.01) in obese compared to control dogs. We conclude that the insulin-stimulated translocation of GLUT4 to the cell surface is reduced in obese female dogs. This probably contributes to insulin resistance, which plays an important role in glucose homeostasis in dogs.

Adipocytes↗

PubMed2002

Low ethanol consumption increases insulin sensitivity in Wistar rats.

Several human studies suggest that light-to-moderate alcohol consumption is associated with enhanced insulin sensitivity, but these studies are not free of conflicting results. To determine if ethanol-enhanced insulin sensitivity could be demonstrated in an animal model, male Wistar rats were fed a standard chow diet and received drinking water without (control) or with different ethanol concentrations (0.5, 1.5, 3, 4.5 and 7%, v/v) for 4 weeks ad libitum. Then, an intravenous insulin tolerance test (IVITT) was performed to determine insulin sensitivity. Among the ethanol groups, only the 3% ethanol group showed an increase in insulin sensitivity based on the increase of the plasma glucose disappearance rate in the IVITT (30%, P<0.05). In addition, an intravenous glucose tolerance test (IVGTT) was performed in control and 3% ethanol animals. Insulin sensitivity was confirmed in 3% ethanol rats based on the reduction of insulin secretion in the IVGTT (35%, P<0.05), despite the same glucose profile. Additionally, the 3% ethanol treatment did not impair body weight gain or plasma aspartate aminotransferase and alanine aminotransferase activities. Thus, the present study established that 3% ethanol in the drinking water for 4 weeks in normal rats is a model of increased insulin sensitivity, which can be used for further investigations of the mechanisms involved.

Alanine Transaminase↗

PubMed2002

Glucose uptake, glucose transporter GLUT4, and glycolytic enzymes in brown adipose tissue from rats adapted to a high-protein diet.

In vivo rates of glucose uptake, insulin-responsive glucose transporter (GLUT4) content, and activities of glycolytic enzymes were determined in brown adipose tissue (BAT) from rats adapted to a high-protein, carbohydrate-free (HP) diet. Adaptation to the HP diet resulted in marked decreases in BAT glucose uptake and in GLUT4 content. Replacement of the HP diet by a balanced control diet for 24 hours restored BAT glucose uptake to levels above those in rats fed the control diet, with no changes in GLUT4 levels in 4 of 5 animals examined. BAT denervation of rats fed the control diet induced a 50% reduction in glucose uptake, but did not significantly affect the already markedly reduced BAT hexose uptake in HP diet-fed rats. It is suggested that the pronounced decrease in BAT glucose uptake in these animals is due to the combined effects of the HP diet-induced reductions in plasma insulin levels and in BAT sympathetic activity. Adaptation to the HP diet was accompanied by decreased activities of hexokinase, phosphofructo-1-kinase, and pyruvate kinase (PK). The activity of BAT PK in HP diet-fed rats was reduced to about 50% of controls, and approached normal levels 24 hours after diet reversion. BAT denervation induced a small (15%) decrease in BAT PK activity in control rats, but did not affect the activity of the enzyme in HP diet-adapted rats. Also, denervation did not interfere with the restoration of PK activity induced by diet substitution. Treatment with anti-insulin serum resulted in an almost 50% reduction in PK activity in both innervated and denervated BAT from rats fed the control diet, but caused a much smaller ( thick approximate 20%) decrease in BAT from HP diet-fed rats. Furthermore, anti-insulin serum administration completely suppressed the restoration of BAT PK activity induced by diet reversion. These data suggest that, differently from glucose uptake, BAT PK activity is predominantly controlled by hormonal/metabolic factors.

Adipose Tissue, Brown↗

PubMed2001

Changes in sodium or glucose filtration rate modulate expression of glucose transporters in renal proximal tubular cells of rat.

Renal glucose reabsorption is mediated by luminal sodium-glucose cotransporters (SGLTs) and basolateral facilitative glucose transporters (GLUTs). The modulators of these transporters are not known, and their substrates glucose and Na+ are potential candidates. In this study we examined the role of glucose and Na+ filtration rate on gene expression of glucose transporters in renal proximal tubule. SGLT1, SGLT2, GLUT1 and GLUT2 mRNAs were assessed by Northern blotting; and GLUT1 and GLUT2 proteins were assessed by Western blotting. Renal cortex and medulla samples from control rats (C), diabetic rats (D) with glycosuria, and insulin-resistant 15-month old rats (I) without glycosuria; and from normal (NS), low (LS), and high (HS) Na+-diet fed rats were studied. Compared to C and I rats, D rats increased (P < 0.05) gene expression of SGLT2 by approximately 36%, SGLT1 by approximately 20%, and GLUT2 by approximately 100%, and reduced (P < 0.05) gene expression of GLUT1 by more than 50%. Compared to NS rats, HS rats increased (P < 0.05) SGLT2, GLUT2, and GLUT1 expression by approximately 100%, with no change in SGLT1 mRNA expression, and LS rats increased (P < 0.05) GLUT1 gene expression by approximately 150%, with no changes in other transporters. In summary, the results showed that changes in glucose or Na+ filtrated rate modulate the glucose transporters gene expression in epithelial cells of the renal proximal tubule.

Animals↗

PubMed2001

Decreased lipolysis and enhanced glycerol and glucose utilization by adipose tissue prior to development of obesity in monosodium glutamate (MSG) treated-rats.

OBJECTIVE: To determine the metabolic alterations that lead to the neonatal administration of monosodium glutamate (MSG), which results in arrested growth and obesity. ANIMALS AND DESIGN: Wistar rats were injected 5 times, every other day, with 4 g of MSG/kg b.w. or with hyperosmotic saline (controls), within the first 10 days of life, and were studied at the age of 30 days. RESULTS: Body weight was lower, whereas adipocyte lipid content, cell diameter, surface area and volume were higher in MSG rats than in controls. Plasma glucose, insulin, NEFA, glycerol and triglyceride levels, and in vitro production of NEFA by lumbar fat pad pieces incubated under basal conditions or in the presence of epinephrine and epinephrine plus glucose in the media were lower in MSG than in control rats. In the same fat pad pieces, the conversion of 1-14C-glycerol into fatty acids was always enhanced and its conversion into glyceride glycerol was enhanced when incubations were carried out in the presence of epinephrine or glucose. Both the hormone sensitive lipase activity and mRNA expression were lower in adipose tissue from MSG rats. Besides, the number of insulin receptors, lipid synthesis from U14C glucose, 3H-2-deoxy D-glucose uptake and cellular GLUT4 translocation index were higher in adipocytes from MSG rats than from the controls. CONCLUSION: It is proposed that an enhanced insulin sensitivity in 1 month old MSG rats is responsible for the decreased lipolytic activity and enhanced glucose uptake. In addition, the enhanced lipogenesis and glycerol reutilization seen in their adipose tissue, disturbs the normal balance between fat depots breakdown and accumulation in favor of the latter.

Adipose Tissue↗

PubMed2001

Increased renal GLUT1 abundance and urinary TGF-beta 1 in streptozotocin-induced diabetic rats: implications for the development of nephropathy complicating diabetes.

Increased expression of transforming growth factor beta-1 (TGF-beta 1) and glucose transporter (GLUT1) has been implicated in the genesis of diabetic nephropathy. The aim of this study was to evaluate GLUT1 protein levels in the renal cortex of a rat model of diabetes as well as its relationship to urinary albumin and TGF-beta1. Streptozotocin-injected rats (n = 13) and controls (n = 13) were compared for their urinary albumin, and TGF-beta 1 and for renal cortical and medullar GLUT1 protein abundance. GLUT1 protein content was determined by optical densitometry after Western blotting using an anti-GLUT1 antibody; urinary albumin was measured using electroimmunoassay, urinary TGF-beta 1 using ELISA. Forty-five days of diabetes resulted in increased albuminuria (p < 0.05), urinary TGF-beta 1 (p < 0.05) and GLUT1 protein abundance (p < 0.05). There was a positive correlation between urinary TGF-beta 1 and plasma glucose levels (r = 0.65, p < 0.05) and albuminuria (r = 0.72, p < 0.05). We concluded that 45 days of diabetes result in incipient diabetic nephropathy and increased cortical GLUT1 protein abundance. We speculate that the higher cortical GLUT1 protein levels in diabetes may amplify the effects of hyperglycemia in determining higher intracellular glucose in mesangial cells, thereby contributing to diabetes-related kidney damage.

Albuminuria↗

PubMed2001

GLUT4 protein expression in obese and lean 12-month-old rats: insights from different types of data analysis.

GLUT4 protein expression in white adipose tissue (WAT) and skeletal muscle (SM) was investigated in 2-month-old, 12-month-old spontaneously obese or 12-month-old calorie-restricted lean Wistar rats, by considering different parameters of analysis, such as tissue and body weight, and total protein yield of the tissue. In WAT, an approximately 70% decrease was observed in plasma membrane and microsomal GLUT4 protein, expressed as microg protein or g tissue, in both 12-month-old obese and 12-month-old lean rats compared to 2-month-old rats. However, when plasma membrane and microsomal GLUT4 tissue contents were expressed as g body weight, they were the same. In SM, GLUT4 protein content, expressed as microg protein, was similar in 2-month-old and 12-month-old obese rats, whereas it was reduced in 12-month-old obese rats, when expressed as g tissue or g body weight, which may play an important role in insulin resistance. Weight loss did not change the SM GLUT4 content. These results show that altered insulin sensitivity is accompanied by modulation of GLUT4 protein expression. However, the true role of WAT and SM GLUT4 contents in whole-body or tissue insulin sensitivity should be determined considering not only GLUT4 protein expression, but also the strong morphostructural changes in these tissues, which require different types of data analysis.

Adipose Tissue↗

PubMed2000

High- or low-salt diet from weaning to adulthood: effect on insulin sensitivity in Wistar rats.

Because of conflicting results in the literature, further studies are needed to confirm an association between the degree of salt consumption and insulin sensitivity. The aim of this study was to measure insulin sensitivity in rats fed from weaning to adulthood with a low (LSD), normal (NSD), or high (HSD) salt diet. Body weight, carcass lipid content, blood glucose, nonesterified fatty acids, plasma insulin, plasma renin activity, and a glucose transporter (GLUT4) were measured. A euglycemic hyperinsulinemic clamp was used in 52 anesthetized rats. Body weight was higher in rats on LSD than in those on NSD (P<0.05) or HSD (P<0.001). Percentage fat carcass content was higher (P<0.05) in rats on LSD than in those on NSD. Basal plasma insulin and glucose levels were not altered (P>0.05) by salt consumption. Nonesterified fatty acids were lower in rats on HSD than in those on LSD (P<0.05) or NSD (P<0.01). Glucose uptake was lower in rats on LSD than in those on NSD (P<0.05) or HSD (P<0. 001). When a euglycemic hyperinsulinemic clamp was used on pair-weight rats, similar results were obtained, which suggests that the effect of LSD on insulin sensitivity was not due to higher body weight. GLUT4 in insulin-sensitive tissues was increased in rats on HSD except in the cardiac muscle. Captopril treatment partially reversed low insulin sensitivity in LSD rats, whereas losartan did not change it, which indicates that the effect of LSD on insulin sensitivity is angiotensin independent. In conclusion, the present results demonstrate that chronic dietary salt restriction induces a decrease in insulin sensitivity not associated with renin-angiotensin system activity or body weight changes.

Aging↗

PubMed1998

Soybean- and olive-oils-enriched diets increase insulin secretion to glucose stimulus in isolated pancreatic rat islets.

Islets isolated from rats fed a lipid-enriched diet have shown an impairment of insulin secretion, but there is no available data comparing the effect of diet containing different dietary fat. This may be important in preventing or facilitating the establishment of diabetes. In this study, the effect of diets enriched (10%) with different fatty acids on insulin secretion by isolated pancreatic islets was investigated. The sources of the fatty acids tested were: saturated long chain from animal fat (AF), polyunsaturated from soybean oil (SO), and monounsaturated from olive oil (OL). The results were compared with those from rats receiving a diet enriched (10%) with a balanced mixture of fatty acids (the same proportion of AF, SO, and OL). The effect of fat-rich diets on insulin release was tested in vivo by giving a glucose load (glucose tolerance test-GTT) and in vitro in perfused islets. The mechanism involved was also examined by measuring 45Ca2+ and 86Rb+ fluxes, GLUT-2 content, and glucose oxidation in isolated islets. A significant increase of insulin secretion and glucose oxidation without any alteration of the ionic movements were detected in islets from SO and OL rats. GLUT-2 content was increased in islets of the OL group but diminished in AF rats. The results led us to postulate that soybean and olive oils may increase the response of insulin secretion to glucose stimulus in pancreatic islets.

Animals↗

PubMed1998

Pinealectomy causes glucose intolerance and decreases adipose cell responsiveness to insulin in rats.

Although the pineal gland influences several physiological systems, only a few studies have investigated its role in the intermediary metabolism. In the present study, male Wistar rats, pinealectomized or sham-operated 6 wk before the experiment, were submitted to both intravenous glucose tolerance tests (IVGTT) and insulin binding as well as glucose transport assays in isolated adipocytes. The insulin receptor tyrosine kinase activity was assessed in liver and muscle. The insulin secretory response during the IVGTT was impaired, particularly in the afternoon, and the glucose transport responsiveness was 33% lower in pinealectomized rats. However, no difference was observed in the insulin receptor number of adipocytes between groups as well as in insulin-stimulated tyrosine kinase activity, indicating that the initial steps in the insulin signaling were well conserved. Conversely, a 40% reduction in adipose tissue GLUT-4 content was detected. In conclusion, pinealectomy is responsible for both impaired insulin secretion and action, emphasizing the influence of the pineal gland on glucose metabolism.

Adipose Tissue↗

PubMed1997

Loss of weight restores GLUT 4 content in insulin-sensitive tissues of monosodium glutamate-treated obese mice.

OBJECTIVE: To investigate the effect of weight loss on GLUT 4 content of insulin sensitive tissues of obese mice. SUBJECTS: Mice were made obese by neonatal treatment with monosodium glutamate (MSG). In addition, one group of obese animals was submitted to a caloric restriction to promote 20% weight loss (MSG-L). Both groups were compared to age-matched control mice. MEASUREMENTS: Anthropometric data, glycaemia and insulinaemia were measured. The GLUT 4 protein was assessed by Western blotting analysis in white (WAT) and brown (BAT) adipose tissue, and skeletal (SM) and cardiac (CM) muscles. RESULTS: The MSG mice were very obese according to their morphometric analysis, showing moderate hyperglycaemia with severe hyperinsulinaemia, and reduced (P < 0.001) glucose/insulin (G/I) ratio. The procedure for weight loss promoted a significant (P < 0.001) reduction of both glycaemic and insulinaemic levels, and an increase in G/I ratio. Compared to control animals, the GLUT 4 content in obese MSG mice, was decreased by 30% (P < 0.05) in SM and CM, by 80% (P < 0.001) in BAT and in different subcellular membrane fractions of WAT. On the other hand, transporter protein content was restored to normal levels in MSG-L animals. CONCLUSION: The reduced GLUT 4 content of insulin sensitive tissues from MSG-treated obese mice is recovered by a 20% loss in weight. This mechanism can be involved in the observed increase of insulin sensitivity.

Adipose Tissue↗

PubMed1997

Baroreflex and chemoreflex dysfunction in streptozotocin-diabetic rats.

Several investigators have demonstrated that streptozotocin (STZ) diabetes induces changes in the autonomic control of the cardiovascular system. Changes in cardiovascular function may be related to peripheral neuropathy. The aim of the present study was to analyze changes in heart rate (HR) and arterial pressure (AP) as well as baroreflex and chemoreflex sensitivity in STZ-induced diabetic male Wistar rats (STZ, 50 mg/kg, i.v., 15 days). Intra-arterial blood pressure signals were obtained for control and diabetic rats (N = 9, each group). Data were processed in a data acquisition system (CODAS, 1 kHz). Baroreflex sensitivity was evaluated by measuring heart rate changes induced by arterial pressure variation produced by phenylephrine and sodium nitroprusside injection. Increasing doses of potassium cyanide (KCN) were used to evaluate bradycardic and pressor responses evoked by chemoreflex activation. STZ induced hyperglycemia (447 +/- 49 vs 126 +/- 3 mg/dl), and a reduction in AP (99 +/- 3 vs 118 +/- 2 mmHg), resting HR (296 +/- 11 vs 355 +/- 16 bpm) and plasma insulin levels (16 +/- 1 vs 57 +/- 11 microU/ml). We also observed that the reflex bradycardia (-16.8 +/- 0.1 vs -12.5 +/- 0.1 bpm/mmHg, in the diabetic group) and tachycardia (-3.68 +/- 0.5 vs -1.75 +/- 0.3 bpm/mmHg, in the diabetic group) produced by vasopressor and depressor agents were impaired in the diabetic group. Bradycardia evoked by chemoreflex activation was attenuated in diabetic rats (control: -17 +/- 1, -86 +/- 19, -185 +/- 18, -208 +/- 17 vs diabetic: -7 +/- 1, -23 +/- 5, -95 +/- 13, -140 +/- 13 bpm), as also was the pressor response (control: 6 +/- 1, 30 +/- 7, 54 +/- 4, 59 +/- 5 vs diabetic: 6 +/- 1, 8 +/- 2, 33 +/- 4, 42 +/- 5 mmHg). In conclusion, the cardiovascular response evoked by baroreflex and chemoreflex activation are impaired in diabetic rats. The alterations of cardiovascular responses may be secondary to the autonomic dysfunction of cardiovascular control.

Animals↗

PubMed1996

Insulin treatment can abolish changes in glucose and glutamine metabolism of lymphocytes and macrophages caused by the implantation of the Walker 256 tumour.

Activation of lymphocytes and macrophages by the implantation of tumour cells (10(7) cells per rat) into the left flank of rats increased the conversion of glucose to lactate and of glutamine to glutamate and aspartate and the decarboxylation of [U-14C]-glucose and [U-14C]-glutamine in incubated cells. In addition, the amount of GLUT1 was increased in macrophages. The effect of insulin treatment on glucose and glutamine metabolism of lymphocytes and macrophages activated by Walker 256 tumour implantation was also examined. For this purpose, insulin was injected subcutaneously (4 U/100 g b.w. daily) after the fourth day of tumour implantation and the rats were killed 10 days afterwards. Insulin treatment fully reverted the changes due to tumour implantation in the metabolism of glucose and glutamine in lymphocytes and of glucose in macrophages.

Animals↗

PubMed1996

Modulation of insulin secretion by feeding behavior and physical activity: possible beneficial effects on obese and aged rats.

The high occurrence of diabetes in aged subjects is well known. In fact, the aging process is accompanied by obesity and presenting increased insulin release and lower peripheral responsiveness to this hormone. A recent study has shown that the changes in glucose utilization and insulin secretion during aging are abolished when obesity is somehow avoided. This fact justifies the effort to define new strategies to avoid the development of obesity during aging. In this review, beneficial effects of balanced diets, high frequency food intake and moderate exercise training on insulin secretion and its effect in rats are presented.

Aging↗

PubMed1994

Reduced content and preserved translocation of glucose transporter (GLUT 4) in white adipose tissue of obese mice.

We investigated glucose transporters (GLUT 1 and GLUT 4) in subcellular membrane fractions of white adipose tissue (WAT) of insulin-resistant obese aurothioglucose (AuTG)- or monosodium glutamate (MSG)-treated mice. In vivo insulin stimulation (0.75 U/kg, EV) promoted, 10 min later, no significant change on glycemia of both AuTG and MSG obese mice, but control mice showed a decrease of 30% (p < 0.001). Basal GLUT 4 content in WAT of obese mice was reduced by 40% (p < 0.001) when compared to that of nonobese mice. Insulin-stimulated GLUT 4 content was significantly (p < 0.01) higher in plasma membrane fraction and lower in microsomal fraction when compared to respective basal values, in all groups. Although the absolute values of GLUT 4 were lower in membrane fractions of obese mice, the relative changes stimulated by insulin were similar among the groups. No effect of obesity or insulin stimulation was observed upon GLUT 1 content. We conclude that WAT of insulin-resistant obese AuTG- and MSG-treated mice has a decreased GLUT 4, but not GLUT 1, content, and the in vivo insulin-stimulated GLUT 4 translocation is preserved.

Adipose Tissue↗

PubMed1994

Modulation of insulin secretion and 45Ca2+ efflux by dopamine in glucose-stimulated pancreatic islets.

1. The effect of dopamine on calcium efflux and insulin secretion is examined in the present study. For this purpose, islets isolated from adult Wistar rats were perfused or incubated at 37 degrees C for 60 min. 2. The results obtained from perfused islets indicate that 100 microM dopamine, in the presence of 5.6 mM glucose, increases insulin secretion and causes a modest elevation of 45Ca2+ efflux. However, glucose stimuli (from 5.6 to 16.7 mM) provoked an unexpected reduction of insulin release, with no alteration in calcium efflux, when 100 microM dopamine was present in the perfusion medium. 3. Similar findings were obtained in incubated islets when the prolonged effect of dopamine was investigated. 4. The observations described above led us to conclude that bioactive amines might play an important role in the modulation of the glucose-induced insulin secretion.

Animals↗

PubMed1993

Decreased glucose transporter (GLUT 4) content in insulin-sensitive tissues of obese aurothioglucose- and monosodium glutamate-treated mice.

We assessed the content of two isoforms of glucose transporter (GLUT 1 and GLUT 4) in insulin-sensitive tissues of hypothalamic obese mice treated with either aurothioglucose (AuTG) or monosodium glutamate (MSG). The animals were studied when obesity had reached a plateau, and they were clearly insulin resistant. We studied different membrane fractions from white adipose tissue (WAT), such as fat-free extract (FFE), plasma membrane (PM) and microsomal (M) fractions. GLUT 4 expressed per protein content displayed a decrease of 50% (p < 0.001) in all membrane fractions of AuTG- and MSG-treated mice. The PM GLUT 4 content, expressed per cell surface area, was reduced by 70% (p < 0.001) in obese mice, and the total FFE GLUT 4, expressed per total fat mass, was 5 times reduced in obese mice. Compared to control mice, obese mice showed a reduction (p < 0.01) of the GLUT 4 amount by 30% (AuTG) and by 40% (MSG) in total membrane fraction (TM) of skeletal and cardiac muscles. Similarly, a reduction of the GLUT 4 amount by 40% (AuTG) and by 45% (MSG) in FFE of brown adipose tissue was observed. The GLUT 1 content in FFE of WAT and TM of skeletal muscle showed no significant difference among the different animal groups. These results confirm a decreased expression of GLUT 4, but not of GLUT 1, in insulin-sensitive tissues, which may contribute to the impaired glucose utilization in these obese animals.

Adipose Tissue↗

PubMed1993

Increased expression of glucose transporter GLUT-4 in brown adipose tissue of fasted rats after cold exposure.

Cold exposure has been shown to increase glucose uptake specifically in brown adipose tissue (BAT), the major site for sympathetically controlled metabolic heat production. In this study, the relationship between glucose uptake and glucose transporters (GLUT) was examined in rats exposed to cold for various periods. To minimize the stimulatory effect of circulating insulin, all animals were starved for 20-24 h before the measurements. Acute (4 h) cold exposure had no effect on protein and mRNA levels of GLUT-4, the predominant isoform of GLUT in BAT, despite a significant increase in cellular glucose uptake. Prolonged (1-10 days) cold exposure produced a parallel increase in GLUT-4 expression and glucose uptake in BAT. In contrast, cold exposure had no noticeable effect on GLUT-1, another isoform of GLUT in BAT, and on GLUT-4 in other insulin-sensitive tissues such as white adipose tissue and muscles. The increased glucose uptake and GLUT-4 expression were completely abolished after surgical sympathetic denervation. These findings suggest that cold exposure increases glucose uptake in BAT by at least two distinct mechanisms, both of which are dependent on sympathetic nerve: 1) an increase in the amount of GLUT-4 due to the stimulation of its de novo synthesis, and 2) an increase without stimulation of GLUT synthesis, probably due to the change in the transport activity of GLUT-4 and/or its translocation from an intracellular pool to the plasma membrane.

Adipose Tissue↗