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

Plasma glucose concentration was measured at 3-h intervals in streptozotocin-induced diabetic rats placed on various insulin replacement regimens using three different kinds of insulin. High insulin dosages produced at least periodic hypoglycemia, even though there were no overt signs of insulin overdose. Low- and single-dose regimens produced periods of hyperglycemia. Both high and low doses of protamine zinc insulin normalized diabetes-induced reductions in 5-hydroxyindole-3-acetic acid [5-HIAA; the principal metabolite of 5-hydroxytryptamine (5-HT)] and 5-HT turnover (5-HIAA/5-HT), despite the failure of the low-dose regimen to normalize plasma glucose. Diabetic rats evidenced continued hyperphagia and hyperdipsia during insulin treatment, and insulin treatment also induced hyperphagia and excessive weight gain in nondiabetic rats. Insulin treatment only partially normalized diabetes-induced adrenal hypertrophy. Adrenal hypertrophy is an indication of a continued stresslike physiological state in diabetes even during insulin therapy. This state may be involved in the enhanced risk in diabetic humans for development of anxiety disorders and clinical depression.
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PMID:Metabolic and neurochemical profiles in insulin-treated diabetic rats. 750 9

(5-(3-Thienyl)tetrazol-1-yl)acetic acid (TAT), a novel potent aldose reductase inhibitor, was administered for 4 weeks to rats with streptozotocin-induced diabetes. Physiological and biochemical studies were subsequently conducted on rat nerve tissue and erythrocyte sorbitol content was estimated. Sciatic nerve blood flow (SNBF) was markedly lower (about 43.4%) in untreated diabetic (DC) rats than in non-diabetic controls (NC). A significant delay in caudal motor nerve conduction velocity (MNCV) and significantly higher glucose, sorbitol and fructose values were observed in the sciatic nerve, accompanied by a markedly higher sorbitol concentration in erythrocytes. In contrast, TAT-treated diabetic groups (DT-10, DT-40 and DT-200) had significantly higher SNBF, MNCV and sciatic nerve myo-inositol values and lower sciatic nerve sorbitol and fructose levels and erythrocyte sorbitol concentration than the DC group. There were good correlations between SNBF and MNCV (r = 0.672, P < 0.001) and between SNBF and erythrocyte sorbitol (r = 0.455, P < 0.003). These findings suggest that both vascular and metabolic factors play an important role in diabetic neuropathy and the effect of aldose reductase inhibitors on diabetic neuropathy may be mediated by at least these two factors.
Diabetes Res Clin Pract 1995 Feb
PMID:Effect of a potent new aldose reductase inhibitor, (5-(3-thienyltetrazol-1-yl)acetic acid (TAT), on diabetic neuropathy in rats. 760 48

The antinociceptive potencies of 2-methyl-4 alpha alpha-(3-hydroxyphenyl)-1,2,3,4,4a,5,12,12 alpha alpha-octahydro-quinolino[2,3,3-g]isoquinoline (TAN-67), a non-peptidic delta-opioid receptor agonist, were examined using the acetic acid abdominal constriction test and the tail-flick test in diabetic mice. TAN-67, at doses of 3-100 mg/kg, s.c. [corrected], produced a marked and dose-dependent inhibition of the number of acetic acid-induced abdominal constrictions in both non-diabetic and diabetic mice. The antinociceptive effect of TAN-67 in the acetic acid abdominal constriction test in diabetic mice was greater than that in non-diabetic mice. Indeed, the ED50 (95% confidence limits) value of TAN-67 for the inhibition of acetic acid-induced abdominal constrictions in diabetic mice (6.0 (3.5-10.5) mg/kg) was significantly lower than that in non-diabetic mice (31.4 (14.2-69.4) mg/kg). The antinociceptive effect of TAN-67 was not antagonized by pretreatment with either beta-funaltrexamine, a selective mu-opioid receptor antagonist, or nor-binaltorphimine, a selective kappa-opioid receptor antagonist. When 7-benzylidenenaltrexone (0.3 mg/kg, s.c.), a selective delta 1-opioid receptor antagonist, was administered 10 min before treatment with TAN-67, the antinociceptive effect of TAN-67 was significantly antagonized. However, naltriben, a selective delta 2-opioid receptor antagonist, had no significant effect on the antinociceptive effect of TAN-67. Furthermore, in the tail-flick test, TAN-67 at doses of 3-30 mg/kg, s.c. [corrected], also produced a marked and dose-dependent antinociceptive effect in diabetic mice, but not in non-diabetic mice. In conclusion, TAN-67 produced an antinociceptive effect through the activation of delta 1-opioid receptors. Furthermore, the results of this study support our hypothesis that mice with diabetes are selectively hyperresponsive to delta 1-opioid receptor-mediated antinociception.
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PMID:Antinociceptive effects of the selective non-peptidic delta-opioid receptor agonist TAN-67 in diabetic mice. 778 82

The effects of propionyl-L-carnitine (PCAL) on caudal motor nerve conduction velocity, the coefficient of variation of the R-R interval on the electrocardiogram, and sciatic nerve blood flow were compared with those of [5-(3-thienyl)tetrazol-1-yl] acetic acid monohydrate, an aldose reductase inhibitor, in rats with streptozotocin-induced diabetes. Diabetic control rats showed significantly delayed nerve conduction (P < .05), decreased R-R variability (P < .05) and reduced sciatic nerve blood flow (P < .05). Oral administration of PCAL (0.5 g/kg/day) and [5-(3-thienyl)tetrazol-1-yl] acetic acid monohydrate (0.05% in the diet: 60 mg/kg/day) for 8 weeks significantly improved both nerve conduction (P < .05) and R-R variability (P < .05) in diabetic rats, along with the normalization of sciatic nerve blood flow. PCAL treatment increased the nerve tissue levels of carnitine and myo-inositol and reduced the serum triglyceride level in diabetic rats. Our results suggests that PCAL could have therapeutic potential for the treatment of diabetic neuropathy.
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PMID:Effect of propionyl-L-carnitine on motor nerve conduction, autonomic cardiac function, and nerve blood flow in rats with streptozotocin-induced diabetes: comparison with an aldose reductase inhibitor. 855 55

Although hypoglycemic doses of insulin (0.24-7.5 U/kg s.c.) did not significantly change acetic acid-induced writhing in mice, they dose-dependently attenuated formalin-induced nociceptive responses, and their effects were more potent on the second phase (ID50 = .62 U/kg) than on the first (ID50 > 7.5 U/kg). Intracerebroventricular doses of insulin (250-1000 microU/animal) mimicked the effects of the s.c. dose, but caused little change in blood glucose levels. The antinociceptive activity of insulin (0.75 U/kg, s.c.) in the formalin test was significantly inhibited by naloxone (10 mg/kg i.p., an opiate receptor antagonist), sulpiride (10 mg/kg i.p., a dopamine 2 receptor antagonist), pindolol (1 mg/kg i.p., a 5-hydroxytryptamine 1 receptor antagonist) and ketanserin (1 mg/kg i.p., a 5-hydroxytryptamine 2 receptor antagonist), but not by 3-tropanyl-indole-3-carboxylate (1 mg/kg i.p., a 5-hydroxytryptamine 3 receptor antagonist). Insulin also exerted antinociception in streptozotocin-induced diabetic mice and genetically diabetic db/db mice which, however, were less sensitive (ID50s around 7.5 U/kg) to the of insulin effect than normal mice. The results suggest that insulin attenuates chronic rather than acute pains through a mechanism mediated by dopamine, 5-hydroxytryptamine and opioids. The antinociceptive pathway appears to be deranged by diabetes mellitus.
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PMID:Insulin attenuates formalin-induced nociceptive response in mice through a mechanism that is deranged by diabetes mellitus. 910 12

Nonenzymatic glycosylation (glycation) of proteins, often referred to as the Maillard reaction, has been proposed to play a role in age and diabetes-related processes by forming protein and DNA adducts and cross-links. These cross-links may contribute to erectile dysfunction by scavenging nitric oxide, which is needed for erection. As the basis for a possible role of the advanced Maillard reaction in age-related erectile dysfunction, we investigated the presence of the specific advanced glycation endproduct (AGE) pentosidine in penile corpus cavernosum tissue and penile tunica albuginea tissue as a function of age. A total of 23 penile tissue specimens were obtained at autopsy, from which 19 samples of tunica albuginea and 21 samples of corpus cavernosum were derived. In addition, 13 penile corporal and tunical specimens were procured at the time of insertion of a penile prosthesis, from which 12 tunica albugineal specimens and 10 samples of corpus cavernosum were derived. Collagen was extracted with acetic acid and pepsin digestion, and the final insoluble collagen product was acid-hydrolyzed with 6 N HCL for 24 h at 110 degrees C. Pentosidine was quantified by high-performance liquid chromatography using a reverse-phase column. The level of pentosidine (expressed in picomoles per milligram of insoluble collagen) was found to increase with age in cadaver as well as living penile corporal and tunical albugineal tissues. Best-fit analysis revealed an exponential increase in both types of cadaver penile tissue, with regression equations of y = 15.29 x 10(9.9e-3x), R2 = 0.79, being obtained in the tunica and y = 13.2 x 10(7.63e-3x), R2 = 0.56, in the corpora. These correspond to 6- and 4-fold increases in pentosidine levels from puberty to the age of 100 years (P < 0.05), respectively. Mean pentosidine levels were higher in the tunica than in the corpora. Comparison of pentosidine levels in the tunica versus the corpora revealed a weakly linear correlation (y = 24.88 + 1.08x, R2 = 0.32). Levels in the tunical and corporal specimens from the living human specimens fell with the predicted confidence intervals of the cadaveric tissue. Tunical specimens from patients who underwent repair or revision of a previously inserted penile prosthesis had very low levels of pentosidine. The exponential age-related increase in pentosidine observed in both types of penile tissue suggests an impairment of collagen turnover, which could be related to the advanced glycation reaction in aging. It is not known whether pentosidine itself is directly associated with erectile dysfunction, but its formation is usually accompanied by extensive tissue modification. Formation of advanced Maillard reaction products, which is greatly accelerated in aging, diabetes, and uremia, could contribute to erectile dysfunction in these syndromes.
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PMID:Age-related increase in an advanced glycation end product in penile tissue. 911 57

The effect of an aldose reductase inhibitor, [5-(3-thienyl) tetrazol-1-yl] acetic acid (TAT), on the electroretinogram was determined in rats with streptozotocin-induced diabetes. Laboratory chow containing 0.05% TAT was given to rats for 2 months, while other diabetic rats were untreated. Groups of TAT-treated and untreated normal rats were also studied. Treatment with TAT produced significant improvement of the electroretinogram. TAT shortened the peak latencies of the b-wave oscillatory potentials, which were significantly prolonged in untreated diabetic rats (P < 0.0001 vs. untreated normal rats). This was accompanied by a significant decrease in the retinal sorbitol and fructose concentrations (by 46.5% and 25.7%, respectively). TAT treatment of diabetic rats also markedly reduced ADP-induced platelet aggregation and significantly increased the red blood cell 2,3-diphosphoglycerate level, accompanied by a marked reduction in sorbitol and fructose concentrations of platelet and red blood cells. There were significant correlations between the summed b-wave peak latencies and platelet aggregation or the 2,3-diphosphoglycerate level in diabetic rats. These findings suggest that an aldose reductase inhibitor, TAT, has therapeutic value for diabetic retinopathy.
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PMID:Effect of an aldose reductase inhibitor on abnormalities of electroretinogram and vascular factors in diabetic rats. 917 54

We estimated the glomerular filtration rate in 33 patients from our diabetic clinic using three methods: the creatinine clearance measured from a timed urine sample and a serum creatinine; the creatinine clearance calculated from the serum creatinine according to the formula of Cockcroft and Gault; and, the plasma clearance of ethylenediaminetetra-acetic acid (EDTA) labeled with 51Cr ([51Cr]EDTA). We repeated the measurements in seven subjects. The measured creatinine clearance was not reproducible. The other two methods were correlated, but not according to the formula y = x. The calculated creatinine clearance significantly underestimated the [51Cr]EDTA clearance particularly at higher [51Cr]EDTA clearance rates. [51Cr]EDTA clearance has been shown by others to parallel, but underestimate, inulin clearance, the optimal method of estimating glomerular filtration rate but difficult to perform in routine practice. Accurately measuring renal function in routine clinical practice is difficult, and this must be borne in mind when making clinical decisions based on current measurements.
J Diabetes Complications
PMID:Measuring renal function in patients with diabetes mellitus. 920 99

In order to clarify the effect of exogenous corticotropin-releasing factor (CRF) on catecholaminergic and serotoninergic system activity in the mediobasal hypothalamus-median eminence (MBH-ME) of ewes the changes in extracellular levels of noradrenaline (NA) and serotonin (5HT), and main metabolites of monoamines, 4-hydroxy-3-methoxyphenylglycol (MHPG), 3,4-dihydroxy-phenylacetic acid (DOPAC), homovanilic acid (HVA), and 5-hydroxy-indolo-3-acetic acid (5-HIAA) were quantified in the perfusates collected from MBH-ME. NA, 5-HT and monoamine metabolites in the perfusates were analyzed using high performance liquid chromatography with electrochemical detection. CRF induced a rise in extracellular concentration of NA and 5-HT only in the estrous ewes prior to a preovulatory LH surge. CRF treatment caused a heterogenous effect on extra-cellular concentrations of 5-HT in ewes during the preovulatory LH surge. Except for DOPAC and HVA in some estrous ewes during the preovulatory LH surge, CRF caused an increase in monoamine metabolites levels in the MBH-ME in anestrous and estrous animals. These results indicate that CRF facilities NA release in the MBH-ME during the presurge LH period in ewes, and that CRF increases metabolic activities of the monoaminergic systems in this structure in the anestrous and estrous ewes, except dopaminergic system in the ewes during the preovulatory LH surge. It is suggested that: 1) the responses of monoaminergic systems activity in the MBH-ME to CRF in large degree is dependent upon physiological state of ewes and 2) in some endocrinological phases CRF may affect LHRH and other hypothalamic hormone secretion indirectly by altering monoaminergic system activity in the MBH-ME.
Exp Clin Endocrinol Diabetes 1997
PMID:Extracellular monoamines and their metabolites in the mediobasal hypothalamus--median eminence of anestrous and estrous ewes during CRF treatment. 922 15

To investigate the role of increased polyol pathway activity and hemodynamic deficits in the pathogenesis of diabetic retinopathy in non-insulin-dependent diabetes mellitus (NIDDM), Otsuka Long-Evans Tokushima fatty (OLETF) rats, an animal model of human NIDDM, were given water with or without 30% sucrose and some of them were fed laboratory chow containing 0.03% cilostazol, an anticoagulant, or 0.05% [5-(3-thienyl)tetrazol-1-yl] acetic acid monohydrate (TAT), an aldose reductase inhibitor, for 8 wk. Long-Evans Tokushima Otsuka (LETO) rats were used as nondiabetic controls. The peak latencies of oscillatory potentials of the electroretinogram in sucrose-fed OLETF rats were significantly prolonged compared with those in OLETF rats without sucrose feeding and LETO rats. There was a marked increase in platelet aggregability and a significant decrease in erythrocyte 2,3-diphosphoglycerate in sucrose-fed OLETF rats. Cilostazol significantly improved these parameters without changes in retinal levels of sorbitol and fructose. TAT, however, ameliorated all of these parameters. These findings confirm that the sucrose-fed OLETF rat is a useful animal model of retinopathy in human NIDDM and suggest that cilostazol improved diabetic retinopathy by modifying vascular factors, not by altering polyol pathway activity.
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PMID:Electroretinogram in sucrose-fed diabetic rats treated with an aldose reductase inhibitor or an anticoagulant. 937 83


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