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

Increase in content of glucose in aorta as well as in reducing properties of NAD and NADP coenzymes and alteration in content of cofactor of the sorbitol pathway led to accumulation of sorbitol in streptozotocin-diabetic rats. Administration of nicotinamide into diabetic animals induced an increase in the ratios of NAD+/NADH and NADP+/NADPH, accompanied by a decrease in sorbitol formation occurring in the reaction catalyzed by aldose reductase and stimulation of the sugar oxidation in the reaction catalyzed by sorbitol dehydrogenase. Possible use of nicotinamide for prevention and treatment of vascular lesions in diabetes is discussed.
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PMID:[Nicotinamide coenzyme regulation of the sorbitol pathway of glucose metabolism in the aorta of rats with streptozotocin diabetes]. 315 51

It was found that in the livers of db/db mice with hyperinsulinemia, obesity and non-insulin-dependent diabetes the rates of cholesterol biosynthesis from pyruvate and, to a lesser extent, from acetate and mevalonate as well as of cholesterol ester biosynthesis from pyruvate (but not from acetate and mevalonate) are increased. Presumably, the observed changes are mediated by structural alterations in the CoA reserves, i.e., increase of free CoA to short-chain acyl-CoA and free CoA to long-chain fatty acyl-CoA indices, and of the ratio between enzymatic activities of generation and utilization of NADPH. Treatment of db/db mice with phosphopantothenate, besides eliciting changes in the CoA reserves structure towards normalization and inhibition of NADP-dependent dehydrogenases and pyruvate and 2-oxoglutarate dehydrogenase complexes, causes the diminution of cholesterol and its ester levels in the liver in the absence of any conspicuous changes in the rates of their biosynthesis from pyruvate.
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PMID:[Effect of phosphopantothenate on the biosynthesis of cholesterol and its esters from various precursors in the liver of db/db mice]. 325 47

Sand rats (Psammomys obesus) maintained on a diet providing a free choice between laboratory chow and salt bush (Atriplex halimus) were classified into four groups differing in extent of the diabetic syndrome: A, normoglycemic-normoinsulinemic; B, normoglycemic-hyperinsulinemic; C, hyperglycemic-hyperinsulinemic; or D, hyperglycemic with reduced insulin levels. The metabolic pattern of these groups was characterized by measuring the uptake of fatty acid-labeled, very-low-density lipoprotein-borne triglycerides (VLDL-TG) and [3H]-2-deoxyglucose (2-DOG) into muscle and adipose tissues; incorporation of [14C]alanine into glycogen in vivo; gluconeogenesis from lactate, pyruvate, and alanine in hepatocytes; the effect of insulin on glycogen synthesis from glucose; the oxidation of albumin-bound [1-14C]palmitate and [14C]glucose in strips of soleus muscle; activities of muscle and adipose tissue lipoprotein lipase; and activities of rate-limiting enzymes of glycolysis, gluconeogenesis, and fatty acid synthesis in liver. In group A, uptake of VLDL-TG and activity of lipoprotein lipase were higher in adipose tissue and lower in muscle than in albino rats. In the liver, gluconeogenesis and the activity of phosphoenolpyruvate carboxykinase, as well as lipid synthesis and the activity of NADP-malate dehydrogenase, were higher than in albino rats, whereas activity of pyruvate kinase was lower. In group B, uptake of VLDL-TG by adipose tissue and muscle and lipoprotein lipase activity were similar or higher than in group A. Uptake of 2-DOG by muscle and adipose tissue and activity of liver phosphoenolpyruvate carboxykinase were lower than in group A. In groups C and D, uptake of VLDL-TG and lipoprotein lipase activity in muscle were further increased.(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes 1986 Jun
PMID:Characterization of stages in development of obesity-diabetes syndrome in sand rat (Psammomys obesus). 351 25

In healthy persons, glucose homeostasis maintains blood glucose levels between 70 and 130 mg/dl despite perturbations by meals, fasting, and exercise. Long-term follow-up of diabetic patients has suggested that "good control" of blood sugar levels minimizes the long-term complications of diabetes, such as retinopathy, nephropathy, and atherosclerosis. It now seems likely the products of insulin-independent metabolic pathways in epithelial and endothelial cells leading to polyol formation and protein glycosylation may be factors in the genesis of retinopathy, neuropathy, nephropathy, and premature atherosclerosis of diabetic patients. Dietary complex carbohydrates of various type, including those rich in dietary fiber, which are the cell walls of fruits, vegetables, and cereals, may slow the rate of absorption of glucose from those diets and contribute to a lowering of the postprandial glucose peak. Glycemic responses to various foods compared to glucose have been studied and show a large variation, which is dependent upon gastric emptying, overall effects on rate of hydrolysis and absorption of glucose from food mixtures. Dietary sucrose seems to cause a degree of insulin resistance. The active part of the disaccharide is fructose, which does not elicit an acute insulin response, but appears indirectly to increase insulin levels in both animals and man. Sucrose in animals appears to promote obesity more than glucose because of its lack of stimulation of thermogenesis. Xylitol has been used as a sweetener and as a sugar substitute in total parenteral nutrition. It is a paradox that the most physiological of sugars (glucose) can be a menace at high concentrations. The use of nonphysiological sugars or their derivatives in diabetics and patients with special needs, such as TPN, requires much more investigation to develop a sound rationale in nutrition management.
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PMID:Monosaccharides in health and disease. 352 17

D-Glucose increased the cytosolic NADH/NAD+ ratio (but not the cytosolic NADPH/NADP+ ratio), augmented O2 uptake, raised the ATP/ADP ratio, decreased 86Rb outflow, and stimulated insulin release in tumoral insulin-producing cells of the RINm5F line. L-Leucine and 4-methyl-2-oxopentanoate also stimulated insulin secretion. In the RINm5F cells, as in normal islet cells, the nonmetabolized analogue of L-leucine, 2-aminobicyclo[2,2,1]heptane-2-carboxylic acid (BCH), activated glutamate dehydrogenase, augmented L-[U-14C]glutamine oxidation, and induced a more reduced state of cytosolic redox couples. However, in sharp contrast to either its effect in normal islet cells or that of D-glucose in the tumoral cells, BCH severely decreased O2 uptake, lowered the ATP/ADP ratio, increased 86Rb outflow, and inhibited insulin release in the RINm5F cells. These findings are interpreted to support the concept that the rate of ATP generation represents an essential determinant of the secretory response of insulin-producing cells to nutrient secretagogues.
Diabetes 1987 Feb
PMID:Opposite effects of D-glucose and a nonmetabolized analogue of L-leucine on respiration and secretion in insulin-producing tumoral cells (RINm5F). 354 45

The authors report 5 cases of Total Pancreatectomy (T.P.) treated with Total Parenteral Nutrition (T.P.N.) in which the non-protein calorie supply consisted of lipids and carbohydrates ("dual energy system"). This form of nutrition, which provided a high energy supply with a reduced glucose intake, prevented the problems associated with hypertonic glucose solutions in the unstable diabetes which follows total pancreatectomy. The authors compared these cases with an earlier series of 11 cases of Total pancreatectomy who were not treated with Total Parenteral Nutrition and observed that the patients treated with TPN had a better recovery, a better glucose homeostasis, a reduction in the complications and mortality and a decreased length of stay in hospital.
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PMID:[Value of total parenteral nutrition after total pancreatectomy]. 392 98

With increasing muscle size, incubated or fresh-frozen leg muscles showed a more reduced redox state and slower proteolysis. The ln of these data gave a linear correlation showing faster proteolysis under more oxidized conditions. In incubated diaphragms, the inhibitory effects of insulin and catecholamines on proteolysis were associated with a more reduced state. Fasting, trauma or cortisol treatment led to accelerated proteolysis and a more oxidized state. Long term fasting and refeeding supported this relationship, as did streptozotocin diabetes. Like the NAD+ and NADP+ redox couples, the glutathione couple seemed to fit this relationship. Use of proteinase inhibitors showed that the redox state probably mediated the effects of the various factors on proteolysis rather than vice versa. Muscle contains thioltransferase which catalyzes the formation of glutathione-protein mixed disulfides. We propose that increased formation of oxidized glutathione and its interaction with muscle proteins may act as a signal for the initiation of proteolysis.
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PMID:Relationship of the redox state to muscle protein degradation. 403 47

The activity of hepatic fructokinase increased about 2-fold in desert-derived spiny mice (Acomys cahirinus) and laboratory bred albino mice and rats, maintained on a 50% sucrose diet for 3 months. The role of fructose as the specific inducer was apparent, as 25% fructose diet produced activity increases similar to those of sucrose in contrast to 25% glucose diet. The activity of hexokinase was not affected by the sucrose diet, that of glucokinase rose marginally but those of pyruvate kinase and NADP-malate dehydrogenase rose pronouncedly, especially in the spiny mice. Fructokinase activity increased significantly only after 2 weeks on the diet and continued to rise gradually. The activities of other gycolytic enzymes rose markedly already after 3 days and peaked at about 14 days. Fasting for 48 hr did not influence fructokinase activity while markedly reducing that of glucokinase, pyruvate kinase and NADP-malate dehydrogenase. Streptozotocin diabetes in rats resulted in a 40% reduction in fructokinase activity after 14 days which was restored after 6 days of insulin treatment. The activity increases of other glycolytic enzymes were more marked. However, the fructokinase induction on the sucrose diet was evident also in diabetic rats, suggesting that the insulin and substrate effects are independent. The preference of fructose over glucose phosphorylation capacity was clearly demonstrable in the non-diabetic and diabetic rats and became enhanced on sucrose feeding. The activity of triokinase also increased on the sucrose diet in the 3 rodent species, suggesting a coordinative substrate effect on the induction of these two rate-limiting fructolysis enzymes.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Response of hepatic fructokinase to long-term sucrose diets and diabetes in spiny mice, albino mice and rats. 608 70

L-Asparagine (2-10 mM) failed to affect insulin secretion from rat pancreatic islets incubated in the absence of exogenous nutrient or presence of D-glucose, but caused a dose-related and progressive enhancement of insulin release evoked by L-leucine, 2-aminobicyclo[2,2,1]heptane-2-carboxylate, or 2-ketoisocaproate. The secretory response to the combination of L-asparagine and L-leucine was augmented by theophylline and inhibited in the absence of extracellular Ca2+ or presence of either menadione or methylamine. L-Asparagine augmented leucine-stimulated 45Ca net uptake. The ATP content, rate of O2 uptake, and malate/pyruvate ratio were not significantly different in islets exposed to L-leucine alone or to both L-asparagine and L-leucine, respectively. In the sole presence of L-asparagine, however, the malate/oxalacetate ratio was decreased and the malate/pyruvate ratio increased, relative to basal values. It is proposed that the enhancing action of L-asparagine upon insulin release evoked by L-leucine might be due to an accelerated generation rate of cytosolic NADPH, rather than to any sizable increase in either islet respiration or steady-state cytosolic NADPH/NADP+ ratio.
Diabetes 1984 May
PMID:The stimulus-secretion coupling of amino acid-induced insulin release. Secretory and oxidative response of pancreatic islets to L-asparagine. 637 56

This study examined the effect of an aldose reductase inhibitor (Sorbinil, CP 45634, Pfizer, Sandwich, Kent, United Kingdom) on the metabolite profile of the lens during the first week after induction of diabetes with alloxan. The lens content of sorbitol, fructose, glycerol 3-phosphate, and glucose 6-phosphate was, respectively, 0.33 +/- 0.03, 0.55 +/- 0.05, 0.10 +/- 0.01, and 0.074 +/- 0.006 mumol/g (means +/- SEM) in the control group rising to 12.2 +/- 0.52, 3.20 +/- 0.10, 0.76 +/- 0.10, and 0.200 +/- 0.009 in lenses from alloxan-diabetic rats. Sorbinil treatment (40 mg/kg) decreased the lens content of sorbitol to 0.60 +/- 0.06, fructose to 0.85 +/- 0.08, and glycerol 3-phosphate to 0.36 +/- 0.03 mumol/g; glucose 6-phosphate remained unchanged. Significantly, the lens content of glutathione was decreased to 60% of the normal value in the diabetic group, but was sustained at normal levels with Sorbinil treatment. The ATP content of the lens was not altered by diabetes or Sorbinil treatment at this time interval. Sorbinil has no significant effect on the above metabolites in the normal rat lens. The effect of Sorbinil in restoring normal levels of glutathione and glycerol 3-phosphate may be a potentially important facet of the action of this drug. The interlocking of metabolic pathways by the redox state of NAD+/NADH and NADP+/NADPH, their derangement in diabetes, and the wider effects of Sorbinil on the network of reactions in the lens are discussed.
Diabetes 1983 May
PMID:The effect of an aldose reductase inhibitor (Sorbinil) on the level of metabolites in lenses of diabetic rats. 640 81


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