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

In islets from adult rats injected with streptozocin during the neonatal period, the oxidative and secretory responses to D-glucose are more severely affected than those evoked by L-leucine. A possible explanation for such a preferential defect was sought by comparing the rate of aerobic glycolysis, taken as the sum of D-[3,4-14C]glucose conversion to labeled CO2, pyruvate, and amino acid, with the total glycolytic flux, as judged from the conversion of D-[5-3H]glucose to 3H2O. A preferential impairment of aerobic relative to total glycolysis was found in islets from diabetic rats incubated at either low or high D-glucose concentration. This coincided in islet mitochondria of diabetic rats with a severe decrease in both the basal (no-Ca2+) generation of 3H2O from L-[2-3H]glycerol-3-phosphate and the Ca2(+)-induced increment in [3H]glycerophosphate detritiation. The mitochondria of diabetic rats were also less efficient than those of control animals in generating 14CO2 from [1-14C]-2-ketoglutarate. The diabetes-induced alteration of 2-ketoglutarate dehydrogenase in islet mitochondria was less marked, however, than that of the FAD-linked glycerophosphate dehydrogenase and was not associated with any change in responsiveness to Ca2+. Sonicated islet mitochondria of diabetic rats displayed normal to slightly elevated glutamate dehydrogenase activity. We propose, therefore, that the preferential impairment of the oxidative and secretory responses of islet cells to D-glucose in this experimental model of diabetes may be at least partly attributable to an altered transfer of reducing equivalents into the mitochondria as mediated by the glycerol phosphate shuttle.
Diabetes 1991 Feb
PMID:Impairment of glycerol phosphate shuttle in islets from rats with diabetes induced by neonatal streptozocin. 182 72

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

The influence of nicotinamide and oxythiamine on the activity of NADPH-producing dehydrogenases of glucoso-6-phosphate, 6-phosphogluconate, malate, isocitrate, as well as concentration and synthesis rate of fatty acids in fatty tissue were studied in experiments on mice with genetically conditioned non-insulin-dependent diabetes and hyperinsulinemia. It has been established that in these diseases the synthesis of fatty acids and their inclusion into lipids are activated without increasing the above enzymes activity. It is shown that nicotinamide and oxythiamine inhibit inclusion of C from glucose into free fatty acids, antivitamin intensifies lipolysis in the fatty tissue of the diseased animals.
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PMID:[Effects of nicotinamide and oxythiamine on the lipogenic parameters of the adipose tissue of mice with non-insulin-dependent type of experimental diabetes mellitus and hyperinsulinemia]. 183 Jul 11

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

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

Biochemical alterations in the hearts of non-diabetic and 5 weeks of streptozotocin-induced diabetic rats following isoproterenol (ISO) administration were compared. Serum lactate dehydrogenase (LDH) and myocardial adenosine triphosphate (ATP), creatine phosphate (CP), lactate and glycogen were used as indices of myocardial injury. Hearts from diabetic rats (blood glucose greater than 350 mg/dl), before ISO administration, had normal lactate levels but significantly low high-energy phosphate (HEP) levels and high glycogen levels in comparison to non-diabetic rats. No difference was observed in serum LDH levels between these two groups. ISO administration to non-diabetic rats caused myocardial necrosis as evidenced by a significant depletion of myocardial glycogen and HEPs along with significant myocardial lactate accumulation and an increase in serum LDH. However, the hearts from diabetic rats failed to show any significant HEP depletion, accumulation of lactate and leakage of LDH into serum following ISO-administration, though myocardial glycogen level was significantly lowered. These observations, in conjunction with earlier reports, point to the hypothesis that, in diabetes, there are certain alterations in the sarcolemma which hamper the process by which ISO causes myocardial necrosis.
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PMID:Isoproterenol fails to produce myocardial necrosis in streptozotocin-induced diabetic rats. 183 21

This study was designed to determine if the known decrease in slow axonal transport of proteins in the sciatic nerve of experimentally diabetic rats is related to altered phosphorylation of neurofilament proteins (NFPs). Rats were rendered diabetic with 50 mg/kg of streptozotocin, i.p. At 3 and 6 weeks later, NFPs were prepared from spinal cord. The in vivo phosphorylation state of NFPs was examined by using phosphate-dependent (RT97) and -independent (RMd09) antibodies against high-molecular-mass NFPs on Western blots. Neurofilament-associated kinase activity was also measured in vitro by incubation of NFPs with [32P]ATP. Phosphorylation of all three NFPs (high, medium, and low molecular mass) occurred, as confirmed by gel electrophoresis and autoradiography. At 30 min of incubation, protein-bound radioactivity in NFPs from diabetic animals was reduced to 86.7 +/- 3.4 and 54.3 +/- 19.6% of that in nondiabetic animals at 3 and 6 weeks of diabetes, respectively (p less than 0.001 and p less than 0.05, respectively). NFPs were also incubated with acid phosphatase and rephosphorylated. Results showed that the increased in vivo phosphorylation contributed to the decreased in vitro phosphorylation. Extraction of protein kinases and addition back to the NFPs revealed, in addition, a reduced activity in the diabetic animals of the protein kinases measured in vitro.
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PMID:Neurofilament protein phosphorylation in spinal cord of experimentally diabetic rats. 184 79

In 1930 adenosine triphosphate appeared in the literature from W. A. Engelhardt's work on avian erythrocytes. This was an early example of oxidative phosphorylation in intact cells, and it required methylene blue and oxygen. Both Belitser and I realized that the use of Warburg manometers for aeration was critical in order to generate oxidative phosphorylation of glucose in tissue preparations. Test tube techniques did not work. In 1956 we were able to describe a human type of diabetes called "galactose diabetes," in which consumption of human or cows' milk provokes mental retardation. Replacement of human or cows' milk products with "vegetable milk" formula in early infancy can prevent retardation. We determined that the disease results from a defect of galactose-one-phosphate uridylyl-transferase, a hereditary enzyme. This type of enzyme defect, if discovered and treated in early infancy, is a benign molecular disease. Regulation of transport systems in mammalian cell cultures are frequently complex energized systems. Perhaps my greatest surprise in this regard was the mere fact that an all-cis "odd" hexose-D-allose turned out to be a highly intense down-regulator of the hexose transport system. Additions of inhibitors of oxidative phosphorylation (such as oligomycin or di-nitrophenol) arrested the allose-mediated down-regulation. We have reason to suspect that the strong down-regulator is a phosphorylated form of D-allose. Thus ends my story about oxidative energized biological phosphorylation systems.
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PMID:50 years of biological research--from oxidative phosphorylation to energy requiring transport regulation. 188 94

We studied the effect of pyridoxal-5'-phosphate (PAL-P) on protein glycosylation and diabetic nephropathy in NSY mice. In experiment 1, an in vitro model of the browning phenomenon involving the incubation of lysine and glucose was inhibited by PAL-P. In experiment 2, administration of PAL-P to congenitally diabetic NSY mice markedly reduced the thickening of the glomerular basement membrane. These results suggest that PAL-P has the potential to be used for reducing the nephrotic complications of diabetes mellitus.
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PMID:The in vitro and in vivo inhibition of protein glycosylation and diabetic vascular basement membrane thickening by pyridoxal-5'-phosphate. 191 2

Changes in high-energy phosphate content and cardiac contractile function of isolated rat hearts as well as changes in Ca2+ sensitivity and mitochondrial respiration of myocardial skinned fibers were assessed in hereditary cardiomyopathies and in cardiomyopathies induced by chronic treatment with adriamycin or norepinephrine, by autoimmunization, by diabetes, or by creatine deficiency. The sum of ATP and phosphocreatine contents as well as cardiac output at standard load conditions was substantially lower in almost all groups. The common features of cardiac pump failure were mild bradycardia, elevated left ventricular (LV) diastolic pressure, and stiffness that limited cardiac contractile adaptation to volume or resistance loads. The LV diastolic stiffness at maximal functional load was inversely correlated with high-energy phosphate content. Increased myofibrillar sensitivity to Ca2+ and defective function of mitochondrial creatine kinase were found in skinned myocardial fibers. These results suggested that both increased myofibrillar Ca2+ sensitivity and energy deficiency within myofibrils may contribute to increased myocardial stiffness. Increased stiffness limits LV filling but facilitates pressure development, which partly compensates for decreased contractility of cardiomyopathic hearts.
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PMID:Energy-linked functional alterations in experimental cardiomyopathies. 192 52


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