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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Elevated free fatty acid concentrations are known to decrease insulin-mediated glucose uptake, glucose oxidation and glycogen synthesis. In order to determine whether free fatty acids inhibit glycogen synthesis at the level of liver cells, the effects of an infusion of lipids on carbohydrate metabolism were investigated in healthy subjects during a two-step (16.7 and 33.4 mumol/(kg.min) 13C-fructose infusion. Fructose infusion dose-dependently stimulated fructose (measured from 13CO2 production) and net carbohydrate oxidation (measured with indirect calorimetry). It also stimulated systemic 13C glucose appearance, indicating a dose-dependent stimulation of gluconeogenesis. Net glucose output (measured with 6,6 2H glucose) was however not altered. Lipid infusion significantly reduced fructose oxidation (measured from 13CO2 production) at both rates of fructose infusion, but did not alter plasma fructose or lactate concentrations, nor plasma 13C glucose appearance or net glucose production. Non oxidative fructose disposal was increased by 31% (p < 0.05) at the lowest, and by 18% (p < 0.01) at the highest infusion rate. Since nonoxidative fructose disposal corresponds mainly to liver glycogen deposition, these results suggest that lipid infusion increased hepatic glycogen synthesis, and hence that hepatic glycogen synthase is not inhibited by fatty acids.
Diabetes Metab 1999 Sep
PMID:Non oxidative fructose disposal is not inhibited by lipids in humans. 1049 92

Diabetic patients have a greater incidence of restenosis, which has been shown to be related to exaggerated intimal hyperplasia. Hyaluronan (HA) has been shown to be closely involved in arterial smooth muscle cell proliferation and migration, which provoke intimal hyperplasia after balloon catheter injury. Our aim was to determine the effect of fructose feeding, which produces certain characteristics of non-insulin-dependent diabetes (ie, insulin resistance, hyperinsulinemia, and hypertriglyceridemia), on production of HA and hyaluronidase and degradation of HA in rat aorta. Treated rats received fructose (25% in tap water) 12 weeks before balloon catheter injury and 14 days afterward. Fructose-fed rats had hyperinsulinemia and hypertriglyceridemia. Injury increased intima-media wet weight (7.5%) and DNA content (20%) in control rats. This increase was significantly greater in fructose-fed rats (22% for wet weight and 34% for DNA content) and was associated with greater HA and hyaluronidase production (123% and 41%, respectively) than in control rats (49% and 7%, respectively). Determination of HA molecular mass showed that balloon catheter injury increased the number of HA fragments in the aorta of control rats. Normal aorta of fructose-fed rats contained more HA fragments than that of control rats. Injury to the aorta of fructose-fed rats increased HA fragments and induced the appearance of a very-high-molecular-mass (>2000 kDa) HA. In conclusion, fructose treatment, which induced hyperinsulinemia and hypertriglyceridemia, increased HA and hyaluronidase production and HA degradation in injured aorta. This finding suggests that HA, which has been shown to play a crucial role in proliferation and migration of arterial smooth muscle cells, may be involved in the promotional effect of long-term fructose feeding on arterial wall reaction to injury.
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PMID:Increased hyaluronan and hyaluronidase production and hyaluronan degradation in injured aorta of insulin-resistant rats. 1084 61

Fructose-2,6-bisphosphate is responsible for mediating glucagon-stimulated gluconeogenesis in the liver. This discovery has led to the realization that this compound plays a significant role in directing carbohydrate fluxes in all eukaryotes. Biophysical studies of the enzyme that both synthesizes and degrades this biofactor have yielded insight into its molecular enzymology. Moreover, the metabolic role of fructose-2,6-bisphosphate has great potential in the treatment of diabetes.
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PMID:PFK-2/FBPase-2: maker and breaker of the essential biofactor fructose-2,6-bisphosphate. 1116 14

Fructose has been shown to have a catalytic effect on glucokinase activity in vitro; however, its effects on hepatic glycogen metabolism in humans is unknown. To address this question, we used (13)C nuclear magnetic resonance (NMR) spectroscopy to noninvasively assess rates of hepatic glycogen synthesis and glycogenolysis under euglycemic (approximately 5 mmol/l) hyperinsulinemic conditions (approximately 400 pmol/l) with and without a low-dose infusion of fructose (approximately 3.5 micromol. kg(-1). min(-1)). Six healthy overnight-fasted subjects were infused for 4 h with somatostatin (0.1 micromol. kg(-1). min(-1)) and insulin (240 pmol. m(-2). min(-1)). During the initial 120 min, [1-(13)C]glucose was infused to assess glycogen synthase flux followed by an approximately 120-min infusion of unlabeled glucose to assess rates of glycogen phosphorylase flux. Acetaminophen was given to assess the percent contribution of the direct and indirect (gluconeogenic) pathways of glycogen synthesis by the (13)C enrichment of plasma UDP-glucuronide and C-1 of glucose. In the control studies, the flux through glycogen synthase and glycogen phosphorylase was 0.31 +/- 0.06 and 0.17 +/- 0.04 mmol/l per min, respectively, and the rate of net hepatic glycogen synthesis was 0.14 +/- 0.05 mmol/l per min. In the fructose studies, the glycogen synthase flux increased 2.5-fold to 0.79 +/- 0.16 mmol/l per min (P = 0.018 vs. control), whereas glycogen phosphorylase flux remained unchanged (0.24 +/- 0.06; P = 0.16 vs. control). The infusion of fructose resulted in a threefold increase in rates of net hepatic glycogen synthesis (0.54 +/- 0.12 mmol/l per min; P = 0.008 vs. control) without affecting the pathways of hepatic glycogen synthesis (direct pathway approximately 60% in both groups). We conclude that during euglycemic hyperinsulinemia, a low-dose fructose infusion causes a threefold increase in net hepatic glycogen synthesis exclusively through stimulation of glycogen synthase flux. Because net hepatic glycogen synthesis has been shown to be diminished in patients with poorly controlled type 1 and type 2 diabetes, stimulation of hepatic glycogen synthesis by this mechanism may be of potential therapeutic value.
Diabetes 2001 Jun
PMID:Stimulating effects of low-dose fructose on insulin-stimulated hepatic glycogen synthesis in humans. 1137 25

Glucokinase (GK) is required for cellular glucose sensing, although there is a paucity of data regarding its role in the counterregulatory response to hypoglycemia in humans. Because fructose has been shown to modulate GK activity, we examined the effects of an acute infusion of fructose on hypoglycemia counterregulation in seven lean nondiabetic subjects. Using stepped hypoglycemia clamp studies (5.0, 4.4, 3.9, and 3.3 mmol/l target plasma glucose steps, 50 min each), subjects were studied on two separate occasions, without (control) or with co-infusion of fructose (1.2 mg.kg(-1).min(-1)). Fructose induced a resetting of the glycemic thresholds for secretion of epinephrine (3.8 +/- 0.1 mmol/l) and glucagon (3.9 +/- 0.2 mmol/l) to higher plasma glucose concentrations (4.0 +/- 0.1 mmol/l [P = 0.006] and 4.1 +/- 0.1 mmol/l [P = 0.03], respectively). In addition, the magnitude of increase in epinephrine and glucagon concentrations was higher after administration of fructose (48 and 39%, respectively, P < 0.05 for both). The amplification of these hormonal responses was specific because plasma norepinephrine, growth hormone, and cortisol were comparable in both sets of studies. Endogenous glucose production, measured with [3-(3)H]glucose, increased by 47% (P < 0.05) in the fructose infusion studies compared with 14% (P = NS) in the control studies. In addition, glucose uptake was more suppressed with fructose infusion (by 33%, P < 0.05). In concert with these effects of fructose on glucose kinetics, average glucose infusion rate was markedly reduced in the fructose infusion studies during the 3.9-mmol/l glucose step (4.6 +/- 0.9 vs. 7.4 +/- 1.1 micromol.kg(-1).min(-1), respectively, P = 0.03) and during the 3.3-mmol/l glucose step (0.5 +/- 0.1 vs. 5.2 +/- 1.2 micromol.kg(-1).min(-1), respectively, P < 0.001), suggesting more potent glucose counterregulation and improved recovery from hypoglycemia with fructose infusion. We conclude that infusion of a catalytic dose of fructose amplifies the counterregulatory response to hypoglycemia by both increases in hormonal activation and augmentation of glucose counterregulation in humans.
Diabetes 2002 Apr
PMID:Fructose amplifies counterregulatory responses to hypoglycemia in humans. 1191 4

Fructose 2,6-bisphosphate (Fru-2,6-P2) plays an important role in the regulation of major carbohydrate fluxes as both allosteric activator and inhibitor of target enzymes. To examine the role of Fru-2,6-P2 in the regulation of hepatic carbohydrate metabolism in vivo, Fru-2,6-P2 levels were elevated in ADM mice with adenovirus-mediated overexpression of a double mutant bifunctional enzyme, 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase (n = 6), in comparison to normal control mice (control, n = 6). The rates of hepatic glycogen synthesis in the ADM and control mouse liver in vivo were measured using new advances in 13C NMR including 3D localization in conjunction with [1-13C]glucose infusion. In addition to glycogen C1, the C6 and C2-C5 signals were measured simultaneously for the first time in vivo, which provide the basis for the estimation of direct and indirect synthesis of glycogen in the liver. The rate of label incorporation into glycogen C1 was not different between the control and ADM group, whereas the rate of label incorporation into glycogen C6 signals was in the ADM group 5.6 +/- 0.5 micro mol.g-1.h-1, which was higher than that of the control group of 3.7 +/- 0.5 micro mol.g-1.h-1 (P < 0.02). The rates of net glycogen synthesis, determined by the glycogen C2-C5 signal changes, were twofold higher in the ADM group (P = 0.04). The results provide direct in vivo evidence that the effects of elevated Fru-2,6-P2 levels in the liver include increased glycogen storage through indirect synthesis of glycogen. These observations provide a key to understanding the mechanisms by which elevated hepatic Fru-2,6-P2 levels promote reduced hepatic glucose production and lower blood glucose in diabetes mellitus.
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PMID:Elucidation of the role of fructose 2,6-bisphosphate in the regulation of glucose fluxes in mice using in vivo (13)C NMR measurements of hepatic carbohydrate metabolism. 1223 May 53

The aim of the present study was to investigate the association of fructose on microangiopathy in patients with diabetes. Postprandial plasma fructose concentrations and postprandial plasma glucose concentrations were simultaneously measured 3 times within a 24-hour period (2 hours after each meal) in 38 patients with type 2 diabetes that had been admitted to the hospital. The mean postprandial plasma fructose concentrations (MPPF) and the mean postprandial plasma glucose concentrations (MPPG) were calculated. Fructose was measured by gas chromatography-mass spectrometry (GCMS). Based solely on MPPF, we were able to divide the patients into three groups: the high MPPF (31.9 +/- 6.5 micromol/L) group (n = 12), the middle MPPF (21.2 +/- 1.8 micromol/L) group (n = 13), and the low MPPF (15.2 +/- 2.4 micromol/L) group (n = 13). Prevalence and degree of retinopathy and nephropathy were then evaluated in the 3 different groups. A significant correlation was observed in the prevalence of proliferative diabetic retinopathy (PDR) among the 3 MPPF groups (P =.024). The prevalence of PDR was higher in the high MPPF group (75.0%) than in the middle and low MPPF groups (23.1% and 38.5%, respectively). Although not significantly different statistically, the prevalence of all degrees of retinopathy showed a tendency to be higher in the high MPPF group (83.3%) than in the middle and low MPPF groups (46.2% and 46.2%, respectively) (P =.081). Nephropathy prevalence also showed a tendency to be higher in the high MPPF group (66.7%) than in the middle and low MPPF groups (38.5% and 30.8%, respectively), although the differences were not significant. The prevalence of clinical albuminuria was not significantly different among the 3 groups, but there was a tendency for it to be higher in the low MPPF group (30.8%) than in the high and middle MPPF groups (16.7% and 0%, respectively). No significant differences in glycemic indicators and mean duration of diabetes were observed among the 3 groups. The increased prevalence of retinopathy in the high MPPF group suggests that fructose is associated with retinopathy in patients with type 2 diabetes.
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PMID:Postprandial plasma fructose level is associated with retinopathy in patients with type 2 diabetes. 1513 61

Fructose is a major dietary sugar, which is elevated in the serum of diabetic humans, and is associated with metabolic syndromes important in the pathogenesis of diabetic complications. The facilitative fructose transporter, GLUT5, is expressed in insulin-sensitive tissues (skeletal muscle and adipocytes) of humans and rodents, where it mediates the uptake of substantial quantities of dietary fructose, but little is known about its regulation. We found that GLUT5 abundance and activity were compromised severely during obesity and insulin resistance in Zucker rat adipocytes. Adipocytes from young obese (fa/fa), highly insulin-responsive Zucker rats contained considerably more plasma membrane GLUT5 than those from their lean counterparts (1.8-fold per microgram membrane protein), and consequently exhibited higher fructose transport (fivefold) and metabolism (threefold) rates. Lactate production was the preferred route for fructose metabolism in these cells. As the rats aged and become more obese and insulin-resistant, adipocyte GLUT5 surface density (12-fold) and fructose transport (10-fold) and utilisation rates (threefold) fell markedly. The GLUT5 loss was more dramatic in adipocytes from obese animals, which developed a more marked insulin resistance than lean counterparts. The decline of GLUT5 levels in adipocytes from older, obese animals was not a generalised effect, and was not observed in kidney, nor was this expression pattern shared by the alpha1 subunit of the Na+/K+ ATPase. Our findings suggest that plasma membrane GLUT5 levels and thus fructose utilisation rates in adipocytes are dependent upon cellular insulin sensitivity, inferring a possible role for GLUT5 in the elevated circulating fructose observed during diabetes, and associated pathological complications.
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PMID:Fructose transport and metabolism in adipose tissue of Zucker rats: diminished GLUT5 activity during obesity and insulin resistance. 1536 82

Chronic feeding of fructose to normal rats causes impaired glucose tolerance, loss of tissue sensitivity to insulin, hyperinsulinemia and hypertension. alpha-Lipoic acid (LA), a co-enzyme known for its potent antioxidant effects, stimulates insulin-mediated glucose uptake in clinical and experimental diabetes. The purpose of this study was to examine whether LA can mitigate fructose-induced insulin resistance and associated abnormalities. Male Wistar rats of body weights 150-170 g were divided into 4 groups containing 12 rats each. Control rats received a control diet containing starch and water ad libitum. Fructose rats received a fructose-enriched diet (>60% of total calories). Fructose + LA rats received a fructose diet and LA (35 mg/kg b.w.) intraperitoneally. Control + LA rats received a normal diet and LA (35 mg/kg b.w.) intraperitoneally. After the treatment period of 20 days, blood pressure (BP) was measured. Oral glucose-tolerance test, insulin-sensitivity index, urea and creatinine clearance tests, and plasma and urinary sodium and potassium levels were analysed. Kallikrein activity and nitrite content were assayed. Additionally, the activities of RBC-membrane Na(+)/K(+) ATPase and Ca(2+) ATPase enzymes were assayed. Fructose rats showed increased BP, decreased glucose tolerance, decreased insulin sensitivity and altered sodium and potassium levels and renal clearance. LA supplementation mitigated these alterations. The increase in BP was attenuated and the levels of biochemical parameters were brought close to normal. The BP-lowering effect of LA in fructose rats may be related to improvement in insulin sensitivity.
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PMID:Lipoic acid attenuates hypertension and improves insulin sensitivity, kallikrein activity and nitrite levels in high fructose-fed rats. 1556 49

With the prevalence of obesity increasing in the U.S. and elsewhere, the place of carbohydrates in the diet has recently been under closer examination. This has led to the development of methods for analyzing the effects of dietary carbohydrate. Primary among these methods is the glycemic index, a measure of a food's effect on blood glucose levels, which was initially designed as a method for determining suitable carbohydrates for people with diabetes. However, the glycemic index does not address other metabolic issues related to excess sugar consumption. Prominent among these issues is the use of low glycemic index sweeteners, particularly fructose, which is increasingly present in processed food. Fructose is associated with increased adiposity, which may result from its effects on hormones associated with satiety. Other methods of determining "good" carbohydrates have also been developed. The common theme among them is increased nonstarchy vegetables and higher-fiber legumes.
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PMID:Carbohydrates and increases in obesity: does the type of carbohydrate make a difference? 1560 60


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