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

Phosphofructokinase activity was measured in the sciatic nerve of streptozotocin-induced diabetic and nondiabetic rats. Average steady-state phosphofructokinase activity was obtained from three consecutive segments of the mid-femoral region in the left sciatic nerve in both diabetic (4 and 24 weeks) and nondiabetic, age-matched animals. Over time, phosphofructokinase activity significantly decreased (p less than 0.05) with diabetes, with no effect demonstrated within similar age-groups. The accumulation of phosphofructokinase activity was accomplished by ligating the mid-femoral region of the right sciatic nerve for 24 h. Anterograde and retrograde axonal transport of phosphofructokinase was measured in the 3-mm segment proximal and distal to the ligature, respectively. There was a trend (p = 0.0627) towards a decline in net proximal accumulation (mean proximal minus mean background) with age. Net distal (mean distal minus mean background) activity declined by 80% (p less than 0.05) in the control group between 4 and 24 weeks of the diabetic state. However, diabetic animals did not experience the same age-related decline in retrograde transport. The findings suggest that diabetes affects the age-associated evolution of retrograde transport, presumably a reflection of the neuropathy occurring in the distal axon branches, without altering anterograde transport to any appreciable extent.
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PMID:Diabetes affects retrograde but not anterograde transport of sciatic nerve phosphofructokinase in Sprague-Dawley rats. 170 40

The fate of D-[2-3H] glucose and D-[5-3H] glucose in pancreatic islets was simulated in models with or without enzyme-to-enzyme tunnelling of hexose 6-phosphates in the glycolytic cascade. Satisfactory values for the recovery of phosphoglucoisomerase activity, for the ratio between unlabelled D-glucose 6-phosphate and D-fructose 6-phosphate, and for the time course of both 3HOH production from D-[2-3H] glucose and tritiated D-fructose 1,6-bisphosphate generation from D-[5-3H] glucose were only reached in models with enzyme-to-enzyme tunnelling, with emphasis on the coupling between phosphoglucoisomerase and phosphofructokinase.
Diabetes Res 1991 Jan
PMID:Hexose metabolism in pancreatic islets (time course of 3HOH production from tritiated D-glucose in models with and without enzyme-to-enzyme tunnelling). 181 93

Euglycemic (approximately 5.5 mM) hyperinsulinemic clamps were performed on normoglycemic insulin-sensitive (NIS) men and men who were normoglycemic but insulin resistant (NIR) and hyperglycemic and insulin resistant (HIR) (i.e., noninsulin-dependent diabetes mellitus). Insulin was infused at successive rates of 40 and 400 mU.m-2.min-1, and biopsies were obtained from the quadriceps femoris muscles before and after insulin and analyzed for regulators of phosphofructokinase, a rate-limiting enzyme for glycolysis. Glucose disposal and whole body carbohydrate oxidation were markedly lower in NIR and HIR vs. NIS (P less than 0.001 for disposal and oxidation). The alpha-D-glucose 1,6-bisphosphate (G-1,6-P2) content increased almost twofold during the 40-mU insulin infusion (P less than 0.001) without any further change during the 400-mU infusion in NIS men. The increase in G-1,6-P2 in NIR and HIR was only approximately 25 and 50% of the increase observed in NIS during the 40- and 400-mU infusions, respectively. The mean content of G-1,6-P2 was strongly related to the mean rate of carbohydrate oxidation (r = 0.99; P less than 0.001). Because during euglycemic hyperinsulinemia approximately 90% of the glucose utilization is accounted for by skeletal muscle (J. Clin. Invest. 76: 149, 1985), it is likely that whole body carbohydrate oxidation is proportional to carbohydrate oxidation and glycolysis in muscle. The different rates of carbohydrate oxidation between NIS and insulin-resistant men could not be associated with differences in fructose 6-phosphate, fructose 1,6-bisphosphate, fructose 2,6-bisphosphate, Pi, free ADP and free AMP (activators of phosphofructokinase), or ATP and citrate (inhibitors of phosphofructokinase).
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PMID:Relationship between carbohydrate oxidation and G-1,6-P2 in human skeletal muscle during euglycemic hyperinsulinemia. 182 56

Measurements were made of the levels of metabolic intermediates and activities of enzymes of the glycolytic route, pentose phosphate pathway, and polyol pathway in livers and kidneys of NOD mice. A 34% decrease in UDP-glucose, a 40% decrease in glucose-6-phosphate (G6P) and fructose-6-phosphate, and a 75% decrease in fructose-2,6-bisphosphate (F2,6P) were found in the livers of NOD mice. The fall in the level of F2,6P (the important regulator of glycolysis) is accompanied by a 20% reduction in the activity of phosphofructokinase. These changes are in agreement with previously reported liver depletion of glycogen and reduced synthesis of proteins and nucleic acids in the diabetic state. In the kidney, the increase in hexokinase activity is consistent with increased levels of G6P and glycogen content of kidney in diabetes. The decreased level of phosphoribosyl pyrophosphate was reported to be a regulator of kidney growth in the initial period of diabetes but can still be found in NOD mice 6 wk after development of hyperglycemia. The reported changes are similar to those seen in alloxan- or streptozocin-induced diabetic animals, but certain changes are more marked in NOD mice, especially those directed to increase nucleic acid and protein synthesis in the diabetic kidney.
Diabetes 1991 Nov
PMID:Regulation of glucose metabolism in livers and kidneys of NOD mice. 183 2

We have cloned a full-length cDNA for rat-liver-type phosphofructokinase. The similarities of the rat liver-type phosphofructokinase mRNA to the human and mouse counterparts were 94% and 99% in their amino acid sequences and 88% and 94% in the nucleotide sequences of their coding regions, respectively. Rat liver-type phosphofructokinase mRNA was expressed in all tissues examined, but its level was regulated tissue-specifically. The nutritional and hormonal regulations of the mRNA in the liver were examined in comparison with those of two other key glycolytic enzymes, glucokinase and L-type pyruvate kinase. The level of liver-type phosphofructokinase mRNA was essentially unchanged by starvation (72 h) or diabetes. The mRNA level also did not change significantly on refeeding starved rats on a high carbohydrate diet, or treating diabetic ones with insulin. These results suggested that rat liver-type phosphofructokinase mRNA in the liver was not under control of diet or insulin, in contrast to glucokinase and L-type pyruvate kinase.
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PMID:Rat-liver-type phosphofructokinase mRNA. Structure, tissue distribution and regulation. 183 95

Changes in the activities of 6-phosphofructo-1-kinase (PFK, EC 2.7.1.11) in the placenta and jejunal mucosa of pregnant rats during the onset of experimental diabetes induced by streptozotocin were investigated. The concentrations of fructose 2,6-bisphosphate were significantly decreased in the placenta and small intestine of the streptozotocin-induced diabetic rats. The total activities and the activity ratios (activity at 0.5 mM fructose 6-phosphate at pH 7.0/activity at pH 8.0 (v0.5/V] of placental and jejunal PFK of diabetic pregnant and virgin rats were markedly diminished as compared to normal control rats. Also the susceptibility of jejunal and placental PFK to inhibition by ATP was increased in the diabetic virgin and pregnant rats. Administration of insulin in vivo completely reversed the effects of diabetes on the regulatory properties and on the total activities of placental and jejunal PFK. It is suggested that the diminished activity of PFK in the placenta and small intestine of streptozotocin-induced diabetic rats could be the result of the decreased concentrations of fructose 2,6-bisphosphate as well as the effect of insulin on the activity of PFK.
Diabetes Res Clin Pract 1991 Aug
PMID:Regulation of 6-phosphofructo-1-kinase in the placenta and small intestine of pregnant streptozotocin-induced diabetic rats. 183 74

Increased nonesterified fatty acid (NEFA) levels may be important in causing insulin resistance in skeletal muscles in patients with non-insulin-dependent diabetes mellitus (NIDDM). The acute effect of the antilipolytic nicotinic acid analogue Acipimox (2 X 250 mg) on basal and insulin-stimulated (3 h, 40 mU/m2 per min) glucose metabolism was therefore studied in 12 patients with NIDDM. Whole-body glucose metabolism was assessed using [3-3H]glucose and indirect calorimetry. Biopsies were taken from the vastus lateralis muscle during basal and insulin-stimulated steady-state periods. Acipimox reduced NEFA in the basal state and during insulin stimulation. Lipid oxidation was inhibited by Acipimox in all patients in the basal state (20 +/- 2 vs. 33 +/- 3 mg/m2 per min, P less than 0.01) and during insulin infusion (8 +/- 2 vs. 17 +/- 2 mg/m2 per min, P less than 0.01). Acipimox increased the insulin-stimulated glucose disposal rate (369 +/- 49 vs. 262 +/- 31 mg/m2 per min, P less than 0.01), whereas the glucose disposal rate was unaffected by Acipimox in the basal state. Acipimox increased glucose oxidation in the basal state (76 +/- 4 vs. 50 +/- 4 mg/m2 per min, P less than 0.01). During insulin infusion Acipimox increased both glucose oxidation (121 +/- 7 vs. 95 +/- 4 mg/m2 per min, P less than 0.01) and nonoxidative glucose disposal (248 +/- 47 vs. 167 +/- 29 mg/m2 per min, P less than 0.01). Acipimox enhanced basal and insulin-stimulated muscle fractional glycogen synthase activities (32 +/- 2 vs. 25 +/- 3%, P less than 0.05, and 50 +/- 5 vs. 41 +/- 4%, P less than 0.05). Activities of muscle pyruvate dehydrogenase and phosphofructokinase were unaffected by Acipimox. In conclusion, Acipimox acutely improved insulin action in patients with NIDDM by increasing both glucose oxidation and nonoxidative glucose disposal. This supports the hypothesis that elevated NEFA concentrations may be important for the insulin resistance in NIDDM. The mechanism responsible for the increased insulin-stimulated nonoxidative glucose disposal may be a stimulatory effect of Acipimox on glycogen synthase activity in skeletal muscles.
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PMID:Effect of the antilipolytic nicotinic acid analogue acipimox on whole-body and skeletal muscle glucose metabolism in patients with non-insulin-dependent diabetes mellitus. 191 78

This study examined the effect of experimental diabetes on the anterograde and retrograde axonal transport of phosphofructokinase activity. Rats with streptozotocin-induced diabetes of 4 weeks duration showed phosphofructokinase activity accumulation deficits both proximal (53% and 65% in two separate experiments) and distal (80% and 70%) to 24-h sciatic nerve constrictions. There was no significant effect of diabetes on the phosphofructokinase activity per unit length in unconstricted sciatic nerve. Treatment of a group of diabetic rats with the aldose reductase inhibitor, sorbinil, profoundly reduced the concentrations of polyol pathway metabolites (sorbitol and fructose) in sciatic nerve. This effective inhibition of aldose reductase did not alter the accumulation deficits of phosphofructokinase activity on either side of sciatic nerve constrictions. We conclude that short-term experimental diabetes causes impaired axonal transport of phosphofructokinase activity by mechanisms unrelated to aldose reductase.
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PMID:Defects of axonal transport in experimental diabetes that are unrelated to the sorbitol pathway. 243 70

This study examined anterograde and retrograde accumulation of axonally transported 6-phosphofructokinase activity, proximal and distal to sciatic nerve constrictions, in rats with streptozotocin-induced diabetes of 4 weeks' duration. There were deficits in accumulation on both sides of the constriction in untreated diabetic rats (proximal accumulation 66% of controls, p less than 0.05; distal accumulation 32% of controls, p less than 0.01). There was also a reduction in the phosphofructokinase activity per unit length unconstricted sciatic nerve in the untreated diabetic rats (87% of controls, p less than 0.05). Treatment of an age-matched group of diabetic rats with twice-daily insulin prevented all the above changes. There were significant increases, over untreated diabetic rats, in phosphofructokinase activity accumulated at constrictions (p less than 0.01 for both proximal and distal) and in unconstricted nerve (p less than 0.05). Indeed the activities measured in insulin-treated diabetic rats were virtually identical to those of controls. Treatment of a third group of diabetic rats with the aldose reductase inhibitor 'Statil' prevented or attenuated accumulations of polyol pathway metabolites and prevented depletion of myo-inositol in the sciatic nerve. In spite of these indications of effective aldose reductase inhibition, the drug was without effect on the deficits in accumulation of activity at ligatures or unconstricted nerve levels of phosphofructokinase activity. We conclude that short-term experimental diabetes in rats induced defects in both anterograde and retrograde axonal transport of 6-phosphofructokinase activity. These defects were prevented by intensive insulin treatment but were resistant to an effective aldose reductase inhibitor, indicating a lack of involvement of polyol pathway flux in their pathogenesis.
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PMID:Reduced anterograde and retrograde accumulation of axonally transported phosphofructokinase in streptozotocin-diabetic rats: effects of insulin and the aldose reductase inhibitor 'Statil'. 243 2

This study measured axonal transport of 6-phosphofructokinase (PFK) and aldolase activities in the sciatic nerves of rats with short-term streptozotocin-induced diabetes. The diabetic rats showed deficits in anterograde (69% of controls; p less than 0.001) and retrograde (33% of controls; p less than 0.01) accumulations of PFK activity as well as its content per unit length of unconstricted sciatic nerve (86% of controls; p less than 0.05). There were no accumulation deficits in aldolase activity in the nerves of the diabetic rats, although the activity per unit length of unconstricted nerve was deficient (81% of controls; p less than 0.05). Treatment of diabetic rats with mixed bovine brain gangliosides (10 mg/kg of body weight/day, i.p.) did not affect the deficit in PFK activity in unconstricted nerve (84% of ganglioside-treated controls; p less than 0.01), but all the other defects in enzyme activities were prevented completely. The diabetic rats also showed a reduction of 7% (p less than 0.01) in sciatic nerve dry weight per unit length, which was prevented by ganglioside treatment. In contrast, the reduced motor nerve conduction velocity, accumulation of polyol pathway metabolites, and depletion of myo-inositol, characteristic of untreated short-term diabetes, were unaffected by ganglioside treatment.
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PMID:Ganglioside treatment of streptozotocin-diabetic rats prevents defective axonal transport of 6-phosphofructokinase activity. 245 37


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