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

The role of oxidative/reductive balance derangement in the pathogenesis of diabetic microangiopathy has often been discussed in the last few years. Therefore, we decided to evaluate the influence of intensive insulin therapy on selected indicators of free radical production. The levels of plasma hydrogen peroxide (H2O2) and serum malonyldialdehyde (MDA) were estimated in 15 patients with Type 1 and 15 with Type 2 diabetes before and after 2 weeks of intensive treatment. The initial H2O2 and MDA levels in all cases were significantly higher than in controls. After 2 weeks of treatment, the values for both estimated parameters were significantly lower; however, they were still higher than in the control group. Our results seem to confirm the previous suggestions concerning the relation between metabolic disturbances and oxidative stress in diabetic patients.
Diabetes Res Clin Pract 1995 Mar
PMID:Metabolic control quality and free radical activity in diabetic patients. 755 1

To establish a new experimental model of chronic pancreatitis (CP) with diabetes, we investigated pancreatic endocrine function, blood flow, and histopathology in CP induced by repetition of cerulein injection plus water immersion stress in rats. CP rats were treated with water immersion stress for 5 hr and two intraperitoneal injections of 20 micrograms/kg body weight of cerulein once a week for 16 weeks. In the CP group, pancreatic contents of protein, amylase, elastase, and lipase significantly decreased to 64, 38, 23, and 68% of the control group, respectively. In oral glucose tolerance test (glucose 2 g/kg body wt), blood glucose level in the CP group was 212.1 +/- 97.8 mg/dl (mean +/- SD) at 30 min and was significantly higher than the control group (126.3 +/- 15.4 mg/dl)(P < 0.05). Two of seven rats in the CP group showed an obvious diabetic insulin in the CP group was 640.1 +/- 148.7 pM, significantly lower than in the control group (1133.4 +/- 242.0 pM)(P < 0.001). However, insulin content in the pancreas was 12.37 nmol/pancreas). In CP rats, winding and dilatation of surface blood vessels and gland atrophy were evident. Marked fibrosis, fatty changes, and destruction of lobular architecture were also demonstrated microscopically, although the structure of each pancreatic islet was preserved and each islet was fully stained with anti-insulin antibody. In the CP group, pancreatic blood flow by the hydrogen gas-clearance method was 197.6 +/- 33.0 ml/min/100 g, which was significantly less than the control group (276.2 +/- 19.1 ml/min/100 g) (P < 0.001). Thus, we conclude that the CP model induced by cerulein plus stress is a new CP model with diabetes in rats, in which the glucose tolerance was impaired without loss of insulin reserve.
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PMID:New chronic pancreatitis model with diabetes induced by cerulein plus stress in rats. 758 14

The present study was designed to determine the possible significance of a therapeutic dose (0.2 mg) of AO-128 on carbohydrate absorption by measuring the breath hydrogen concentration, which is an index of the amount of unabsorbed carbohydrate in the large intestine. Post-prandial hyperglycemia is common among diabetic patients. AO-128, a potent alpha-glucosidase inhibitor, suppressed post-prandial hyperglycemia and hyperinsulinemia in healthy volunteers at a dose of 0.2 mg with each meal. These volunteers increased the breath hydrogen concentration in response to ingestion of non-absorbable lactulose, but decreased only slightly its concentration from the basal level after sucrose ingestion, indicating complete absorption. When AO-128 (0.2 mg) was given with sucrose, hydrogen production increased only slightly compared with placebo, suggesting that the inhibitory effect of AO-128 on sucrose absorption was minimal. Only 5 g of the 100 g of sucrose was not absorbed and this 5% reduction is too small to explain the observed inhibitory effect on the post-prandial rise in plasma glucose. Sucrose loading in rats (about 443 mg) sharply increased blood glucose and was accompanied by the rapid disappearance of sucrose from the upper small intestine. AO-128 (0.03 or 0.1 mg/kg) lessened the elevation of blood glucose after sucrose ingestion. The lower dose (0.03 mg/kg) retarded small intestinal absorption, but did not induce an influx of sucrose into the cecum and large intestine, while the higher dose (0.1 mg/kg) caused an increased influx of sucrose into the large bowel. These results indicated that AO-128 retards the absorption of carbohydrate and reduces post-prandial hyperglycemia.
Diabetes Res Clin Pract 1995 May
PMID:An alpha-glucosidase inhibitor, AO-128, retards carbohydrate absorption in rats and humans. 758 23

Evidence is accumulating that most of the degenerative diseases that afflict humanity have their origin in deleterious free radical reactions. These diseases include atherosclerosis, cancer, inflammatory joint disease, asthma, diabetes, senile dementia and degenerative eye disease. The process of biological ageing might also have a free radical basis. Most free radical damage to cells involves oxygen free radicals or, more generally, activated oxygen species (AOS) which include non-radical species such as singlet oxygen and hydrogen peroxide as well as free radicals. The AOS can damage genetic material, cause lipid peroxidation in cell membranes, and inactivate membrane-bound enzymes. Humans are well endowed with antioxidant defences against AOS; these antioxidants, or free radical scavengers, include ascorbic acid (vitamin C), alpha-tocopherol (vitamin E), beta-carotene, coenzyme Q10, enzymes such as catalase and superoxide dismutase, and trace elements including selenium and zinc. The eye is an organ with intense AOS activity, and it requires high levels of antioxidants to protect its unsaturated fatty acids. The human species is not genetically adapted to survive past middle age, and it appears that antioxidant supplementation of our diet is needed to ensure a more healthy elderly population.
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PMID:The role of free radicals in disease. 761 52

L-Carnitine metabolism is abnormal in diabetes mellitus, and treatment with acetyl-L-carnitine (ALC) improves the function of cardiac muscle, retina, and peripheral nerve in experimental models. The aim was to compare the effects of ALC and proprionyl-L-carnitine (PLC) on motor and sensory nerve conduction in streptozotocin-diabetic rats and to ascertain whether their action could be mediated by a vascular mechanism. ALC and PLC treatment for 2 months after diabetes induction attenuated the development of sciatic motor nerve conduction velocity (NCV) deficits by 59.4% +/- 4.4% and 46.9% +/- 3.2%, respectively. There was a similar level of protection for sensory saphenous NCV (42.9% +/- 6.6% and 47.8% +/- 6.0%, respectively). Neither ALC nor PLC prevented the development of resistance to hypoxic conduction failure (RHCF) in sciatic nerve from diabetic rats. A 46.5% +/- 3.4% deficit in sciatic endoneurial blood flow, measured by microelectrode polarography and hydrogen clearance, in diabetic rats was partially prevented by both ALC (48.7% +/- 6.4%) and PLC (69.4% +/- 10.1%). ALC had no significant effect on blood flow in nondiabetic rats. Thus, the data show that these L-carnitine derivatives have a similar efficacy in preventing nerve dysfunction, which depends on a neurovascular action.
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PMID:Effects of acetyl- and proprionyl-L-carnitine on peripheral nerve function and vascular supply in experimental diabetes. 766 97

The effects of carvedilol (10 mg kg-1 day-1), a peripheral vasodilator and oxygen free radical scavenger, on nerve conduction and blood flow were examined in streptozotocin-diabetic rats. Rats were treated from induction of diabetes for 1 month in a preventive experiment; effects of treatment in non-diabetic rats were also examined. Diabetes caused a 20.0% (P < 0.001) reduction in sciatic motor conduction and a 14.7% (P < 0.001) deficit in saphenous sensory conduction. Diabetic rats given carvedilol treatment had motor and sensory conduction velocities which did not differ significantly from those of non-diabetic controls, but were greater than for untreated diabetes (P < 0.001). Carvedilol treatment did not significantly alter nerve conduction in non-diabetic rats. The nutritive (capillary) component of sciatic endoneurial blood flow, measured by microelectrode polarography and hydrogen clearance, was 45.8% (P < 0.001) reduced by diabetes. This was completely corrected (P < 0.001) by carvedilol treatment in diabetic rats, flow being in the upper half of the non-diabetic range. In non-diabetic rats, carvedilol caused a 30.6% (P < 0.05) elevation in blood flow. Hydrogen clearance data also revealed a shift away from non-nutritive (arterio-venous anastomotic) towards nutritive flow in treated diabetic rats (P < 0.05). We conclude that the data support a neurovascular hypothesis of diabetic neuropathy. Carvedilol, via vasodilator and anti-oxidant actions, prevents the nutritive blood flow changes that lead to nerve dysfunction.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Neuroprotective effects of carvedilol in diabetic rats: prevention of defective peripheral nerve perfusion and conduction velocity. 767 22

The blood flow volume at the laminar portion of the optic nerve head in alloxan-induced diabetic and normal rabbits was measured employing the hydrogen clearance method. Ten 6-month-old albino rabbits (10 eyes) were rendered diabetic with 10% alloxan monohydrate solution (80 mg/kg, injection into the auricular vein). The rabbits with nonfasting blood glucose levels of more than 200 mg/dl and showing no significant electroretinographic abnormalities during 24 weeks were treated as the diabetic group in this study. At intraocular pressure (IOP) levels from 5 to 15 mmHg, the mean blood flow volume in the diabetic group was almost the same as the volume in the age-matched control group (11 eyes of 11 rabbits). But when the IOP was raised to 25, 35, and 45 mmHg in a stepwise fashion, the mean blood flow volume in the diabetic group significantly decreased, compared with the control group. These findings suggest that blood microcirculation in the optic nerve head may be damaged by ocular hypertension in the early stage of diabetes mellitus without retinopathy.
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PMID:[Optic nerve head circulation in alloxan-induced diabetic rabbits]. 770 86

This study examined the ability of nitrovasodilator treatment with isosorbide dinitrate to prevent the development of reduced nerve conduction velocity and nutritive blood flow in streptozotocin-induced diabetes mellitus in rats. Two month untreated diabetes caused approximately 23% and 13% reductions in sciatic motor and saphenous nerve sensory conduction velocity (P < 0.001). Isosorbide dinitrate treatment provided 64.6 and 67.6% protection for motor and sensory nerves, respectively (P < 0.01). Sciatic endoneurial nutritive blood flow was measured by microelectrode polarography and a hydrogen clearance technique. After 1 month untreated diabetes, flow was reduced by 41.9% (P < 0.001). Isosorbide dinitrate treatment for 1 month in non-diabetic and diabetic rats significantly increased blood flow (P < 0.01). When between-group variations in blood pressure were taken into account, vascular conductance increased by 29% and 31% in non-diabetic and diabetic rats, respectively (P < 0.01). Thus, nitrovasodilator treatment improves nerve perfusion and function in experimental diabetes, probably by compensating for reduced endothelium-derived nitric oxide release or action.
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PMID:Effects of chronic treatment with a nitric oxide donor on nerve conduction abnormalities and endoneurial blood flow in streptozotocin-diabetic rats. 770 82

The effects of glucose concentration on D-glucose oxidation and reduced nicotinamide adenine dinucleotide phosphate (NADPH) supply were studied during exposure of cultured human umbilical vein endothelial cells to hydrogen peroxide (H2O2). The activation of glucose oxidation via the pentose phosphate pathway (PPP), induced by exposure of cells to 200 mumol/l H2O2 for 1 h, was reduced by 50% (P < 0.01) in cells cultured for 5-7 days in 33 mmol/l D-glucose (HG) versus those cultured in 5.5 mmol/l D-glucose without (NG) or with (HR) 27.5 mmol/l D-raffinose. The intracellular NADPH content in HG cells, but not in NG or HR cells, was decreased by 42% (P < 0.01) by exposing cells to 200 mumol/l H2O2. The decrease in NADPH was dependent on D-glucose concentration in the medium and was prevented in glutathione (GSH)-depleted cells. The latter observation suggests that the decrease in NADPH is associated with activation of the GSH redox cycle. In the presence of 200 mumol/l H2O2, lactate release into the medium, NADH/NAD ratio, and phosphofructokinase activity in HG cells were 56, 53, and 68% greater, respectively, than in the NG group, which indicates that inhibition of glycolysis by H2O2 is less marked in the HG group compared with NG group. These results indicate that activation of the PPP was impaired in endothelial cells cultured under conditions of high-glucose and oxidative stress, resulting in a decreased supply of NADPH to various NADPH-dependent pathways, including the GSH redox cycle.
Diabetes 1995 May
PMID:Impaired activation of glucose oxidation and NADPH supply in human endothelial cells exposed to H2O2 in high-glucose medium. 772 9

Microalbuminuria (urinary albumin excretion between 20 and 200 micrograms/min) and abnormalities of red blood cell sodium-hydrogen exchange coexist in essential hypertensive patients. To evaluate how the two phenomena relate, we recruited 10 untreated microalbuminuric male essential hypertensive patients without diabetes to be compared with an equal number of matched essential hypertensive patients excreting albumin in normal amounts as well as 10 healthy control subjects. Sodium-hydrogen exchange values were increased to a comparable extent in microalbuminuric and normoalbuminuric hypertensive patients. Systolic and mean blood pressures were higher in microalbuminuric patients. Fasting insulin was greater and high-density lipoprotein cholesterol lower in patients than control subjects. Urinary albumin excretion correlated positively with both mean blood pressure and left ventricular mass values in the absence of a relationship with circulating lipid and insulin levels. In contrast with microalbuminuria, sodium-hydrogen exchange covaried only with high-density lipoprotein cholesterol and insulin levels. Thus, microalbuminuria and an abnormal sodium-hydrogen exchange are unrelated phenomena in essential hypertensive patients. Microalbuminuria appears to be a hemodynamically driven biological variable, while an accelerated sodium-hydrogen exchange seems primarily conditioned by the metabolic abnormalities of hypertension, possibly in the context of an insulin-resistant syndrome.
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PMID:Microalbuminuria and erythrocyte sodium-hydrogen exchange in essential hypertension. 773 37


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