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

Noradrenaline levels in the superior cervical ganglion and sciatic nerve were significantly reduced in chronic streptozotocin-induced diabetes in rats. Sciatic nerve sheath in vitro biosynthesis of 6-keto prostaglandin F1 alpha (6KPGF1 alpha; the stable metabolite of prostacyclin) was significantly reduced but not in acute experimental diabetes. Nerves with reduced 6KPGF1 alpha had an excessive response to arachidonic acid stimulation. We suggest that the reduced endogenous biosynthesis of prostacyclin is due to reduced substrate availability, possibly due to the reduced noradrenaline. The implications of these findings on the pathogenesis of diabetic neuropathy are discussed. Neuropathy was found to involve all fibre populations studied (motor, sensory and sympathetic) and progressed with duration of diabetes.
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PMID:Prostacyclin and noradrenaline in peripheral nerve of chronic experimental diabetes in rats. 252 6

Retention of one-trial passive avoidance training was compared in diabetic and nondiabetic rats. Also compared were corticosterone concentrations associated with both training and retention testing, catecholamine excretion related to training, and regional brain catecholamine concentrations accompanying retention testing. Diabetic rats showed significantly better retention for the task than did nondiabetic rats. Associated with retention differences, diabetic rats had higher epinephrine excretion and nondiabetic rats had lower excretion after footshock training relative to baseline measures. Norepinephrine excretion was elevated in diabetics both in baseline measurement and during the 24 hr following footshock training. No differences were found in baseline or stimulated corticosterone concentration between diabetic and nondiabetic rats. Diabetic rats had higher concentrations of norepinephrine (NE) and dopamine (DA) and lower 3,4-dihydroxyphenylacetic acid/dopamine (DOPAC/DA) ratios in hypothalamus and higher NE in brain stem and amygdala than did nondiabetics, although both diabetic and nondiabetic rats had reduced DA and NE following retention testing. The results indicate that there are biochemical alterations in diabetes that may have important behavioral impact.
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PMID:Stress and behavior in streptozotocin diabetic rats: biochemical correlates of passive avoidance learning. 252 5

The effects of streptozotocin-induced (STZ) diabetes on neuroendocrine and sexual function were evaluated in adult male rats. Adult male rats were injected with STZ (50 mg/kg) or vehicle and tested for copulatory behavior 7, 14, and 21 days later. The rats were killed 1 month after STZ or vehicle treatment for measurement of plasma hormone levels, hypothalamic catecholamine turnover, LHRH content, and in vitro pituitary function. The STZ rats showed significant deficits in mount, intromission, and ejaculatory behaviors. Plasma levels of testosterone, LH, FSH, and PRL were all significantly reduced in the STZ compared to the control rats, but in vitro LH secretion was enhanced after STZ treatment. In vitro PRL secretion and the inhibitory response to dopamine did not differ between the two groups. The levels of LHRH were reduced in the medial basal hypothalamus (MBH), but LHRH levels in the median eminence (ME) and anterior hypothalamus (AH) were unchanged after STZ treatment. Norepinephrine turnover was reduced in the ME, MBH, and AH of the STZ rats, while dopamine turnover was unchanged in the ME, increased in the MBH, and reduced in the AH of the STZ rats compared to those in the vehicle-treated controls. These results suggest that changes in pituitary and testicular function in rats made diabetic by STZ treatment are secondary to changes in hypothalamic catecholamine metabolism. Changes in copulatory behavior could be due to both reductions in plasma testosterone levels as well as changes in central neurotransmitter metabolism.
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PMID:Streptozotocin-induced deficits in sex behavior and neuroendocrine function in male rats. 252 88

The influence of alloxan-induced diabetes on the adrenergic constriction of the rat cerebral vasculature was investigated in the in situ perfused brain preparation. The preparation was perfused with an artificial medium at a constant flow rate and the change in perfusion pressure was measured. Norepinephrine (NE) and serotonin produced a dose-dependent increase in the perfusion pressure, but only the effect of NE was significantly enhanced in the diabetic rats. Such an enhancement of NE-induced vasoconstriction was not observed in the perfused hindquarter preparations from the diabetic rats. Propranolol (1 microM) potentiated the cerebrovascular constriction by NE and abolished the difference between diabetic and control rats at low doses of NE. However, vasoconstriction by the higher doses of NE in the diabetic rats was still enhanced even in the presence of propranolol. The cerebrovascular constriction by phenylephrine was also enhanced in the diabetic rats, while the vasoconstricting effects of clonidine, xylazine and oxymetazoline were not affected by diabetes. These results suggest that the enhanced cerebrovascular constriction by NE may be due to either the reduced response through beta-adrenoceptors or the enhanced response through alpha 1-adrenoceptors. The enhanced adrenergic constriction of the cerebral vasculature might be concerned with the high incidence of neurological deficit in stroke patients with diabetes.
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PMID:Enhanced adrenergic response of the cerebral vasculature in alloxan-induced diabetic rats. 263 66

Low-protein diets in nondiabetic renal failure may slow the progressive loss of renal function in some patients, but few studies have detailed the nutritional consequences of these diets in patients with diabetic nephropathy. We studied 7 patients with insulin-dependent diabetes mellitus and chronic renal insufficiency [mean +/- SEM creatinine clearance (S, U): 28.3 +/- 6.5 ml/min (0.47 +/- 0.11 ml/s x 1.73/A)] for 15 weeks who were prescribed a diet of 0.6 g protein/kg ideal body weight. Midarm muscle circumference (24.1 +/- 1.8 at onset vs. 24.5 +/- 1.5 cm at completion), triceps skinfold thickness (21.6 +/- 3.1 vs. 21.0 +/- 1.5 mm), body weight (71.8 +/- 4.1 vs. 71.2 +/- 4.6 kg), and serum albumin [3.0 +/- 0.1 vs. 3.2 +/- 0.1 g/dl (30 +/- 1 vs. 32 +/- 1 g/l)] remained stable. Based on urinary nitrogen excretion, diet diaries overestimated the degree of dietary protein restriction; there was good adherence to the diet as evidenced by a reduction in urinary urea nitrogen (average 32%). Blood glucose control was maintained despite increased carbohydrate intake. On average, creatinine clearance did not change significantly, but proteinuria diminished slightly (1.8 +/- 0.2 vs. 1.5 +/- 0.6 g/day). These results indicate that 0.6 g/kg/day protein diets did not cause protein depletion in insulin-dependent diabetic patients. Longer-term studies are indicated to assess more fully the efficacy of these dietary regimens in reducing proteinuria or benefiting diabetic nephropathy.
Nephron 1989
PMID:Protein-restricted diets in diabetic nephropathy. 271 Feb 67

The etiology of autonomic neuropathy in insulin-dependent diabetes mellitus (IDDM) is unknown. Previous studies have noted the presence of anti-adrenal medullary antibodies in IDDM. Recently, we have also demonstrated the presence of anti-sympathetic ganglia antibodies in IDDM. We initiated a study to evaluate whether subjects with complement-fixing anti-adrenal medullary (CF-ADM) and anti-sympathetic ganglia (CF-SG) antibodies have a decreased catecholamine response to change in posture. Seven IDDM subjects aged 19-41 yr with duration of disease 5-21 yr at the time of the posture study were evaluated. Serums collected longitudinally were evaluated for the presence of CF-ADM and CF-SG antibodies. Three IDDM subjects were CF-ADM- and CF-SG- at all testing intervals (Ab- group). Four IDDM subjects were CF-ADM+ and/or CF-SG+ on at least one testing date (Ab+ group). Baseline mean norepinephrine and epinephrine levels were not significantly different in Ab+ and Ab- subjects. Norepinephrine levels 5 min after standing were mean +/- SD 227 +/- 16 and 419 +/- 48 pg/ml for Ab+ and Ab- subjects, respectively (P less than .03). The means of the 5-min minus basal norepinephrine levels were 88 +/- 42 (Ab+) and 207 +/- 26 (Ab-) pg/ml (P less than .03). Mean epinephrine levels after 5 min of standing were 35 +/- 16 (Ab+) and 101 +/- 44 (Ab-) pg/ml (P less than .03). The means of the 5-min minus basal epinephrine levels were 1 +/- 5 (Ab+) and 43 +/- 38 (Ab-) pg/ml (P less than .03).(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes 1989 Jul
PMID:Anti-sympathetic nervous system autoantibodies. Diminished catecholamines with orthostasis. 273 66

From 1978 through 1984, the incidence of treated end-stage renal disease (ESRD) secondary to diabetic nephropathy increased from 3 to 19 per million population among the membership of the Kaiser Permanente Medical Care Program in Northern California. Forty-eight percent had type II diabetes. Among 66 type II diabetics retinopathy was less severe and hypertension was more frequent than among 50 type I diabetics. Blacks were represented in a higher proportion than expected from their proportion of the health plan membership. Among type II diabetics who developed ESRD, once proteinuria occurred, nephropathy progressed at the same rate observed in type I diabetics. This observation suggests that the clinical progression of diabetic nephropathy may be similar for both types of diabetes after the development of proteinuria, but requires prospectively collected data for confirmation.
Nephron 1989
PMID:Comparison of type II and type I diabetics treated for end-stage renal disease in a large prepaid health plan population. 273 29

The chronic hyperglycemia in diabetes mellitus enhances the nonenzymic glycation of structural proteins possibly increasing the formation of highly reactive advanced glycation end products (AGE). These protein changes might be involved in tissue-damaging mechanisms leading to diabetic complications, including diabetic nephropathy. To simulate these events, an in vitro model, based on isolated human glomerular basement membrane (hGBM), has been developed. In this study we have investigated the extent of AGE formation and the binding changes induced by the nonenzymic glycation of hGBM. An enriched fraction of hGBM was isolated from normal human kidneys and glycated in vitro by incubation with glucose (500 mmol/l) at 37 degrees C for 10 days. The presence of AGE was investigated by two methods - spectrofluorescence and the diazonium salt reaction - both specific for this type of chemical entity. The binding capacity of glycated hGBM was tested by a 10-day incubation with human insulin, albumin, immunoglobulin G and fibrinogen. Higher relative spectrofluorescence values at 440 nm emission (20.0 +/- 2.0 vs. 12.5 +/- 5.0) and higher absorbance values at 492 nm (0.798 +/- 0.063 vs. 0.429 +/- 0.228) indicated the presence of increased levels of AGE in glycated vs. native hGBM. Insulin and the three proteins were bound to hGBM in increased amounts after its glycation (p less than 0.05). The results obtained in this in vitro model confirm that enhanced nonenzymic glycation of hGBM induces the formation of AGE and possibly, through these compounds, alters its physicochemical and binding properties. This reaction might contribute to the mechanisms eventually leading to diabetic nephropathy.
Nephron 1989
PMID:Nonenzymic glycation of isolated human glomerular basement membrane changes its physicochemical characteristics and binding properties. 273 62

The purpose of this investigation was to study in a group of diabetics with varying degrees of renal failure, the relationship of renal size to the degree of renal function. A literature search of the past 25 years has failed to document a precise relationship between structure and function in this setting. Patients were admitted, and sex, age, race, serum creatinine levels, renal size and mean blood pressure were ascertained. Patients with polycystic kidney disease were, obviously, excluded. The group consisted of 26 diabetics, divided into two groups based on previous (prior to onset of uremia) insulin and ketone status. Interestingly, there was no significant difference between groups with insulin-dependent diabetes mellitus (IDDM) and non-insulin-dependent diabetes mellitus (NIDDM) as regards mean blood pressure (106.5 +/- 15.3 mm Hg vs. 108.9 +/- 17.64 mm Hg; t = 0.3607892, p = 0.9). Mean kidney length was inversely related to serum creatinine level (r = 0.3980, n = 26, p less than 0.05). There was no correlation between mean renal length and mean blood pressure (r = 0.189, p greater than 0.05). However, there was a significantly higher proportion of larger kidneys (11 cm or more) in the IDDM group than in the NIDDM group (Fischer's exact test; p less than 0.0001) which was related neither to age nor blood pressure. In this paper, we show an inverse correlation between kidney length and serum creatinine.(ABSTRACT TRUNCATED AT 250 WORDS)
Nephron 1989
PMID:Renal size and function in diabetic nephropathy. 273 65

Recent studies in man demonstrated a marked ketogenic effect of increased plasma norepinephrine concentrations as observed in diabetic ketoacidosis. Since this effect may have been due either to increased substrate supply for ketogenesis (lipolysis) or to direct hepatic activation of ketogenesis, the latter mechanism was examined in isolated rat hepatocytes. Incubation of hepatocytes with norepinephrine (10(-7) to 10(-4) M) resulted in a dose-dependent increase in conversion of the long-chain fatty acid [1-14C]palmitate into ketone bodies and CO2. Norepinephrine decreased [1-14C]palmitate conversion into triglycerides without affecting fatty acid uptake. Norepinephrine enhanced ketogenesis from [1-14C]palmitate in a physiologic range of fatty acid concentrations (0.5-2.5 mM), but failed to affect fatty acid esterification to phospholipids or mono- and diglycerides. In contrast to long-chain fatty acids, oxidation of the medium-chain fatty acid [1-14C]octanoate to ketone bodies was not enhanced by norepinephrine, whereas CO2 production increased. The effect of norepinephrine on [1-14C]fatty acid oxidation was blocked by the alpha 1 receptor blocker prazosin. The results demonstrate that norepinephrine diverts long-chain fatty acids into the pathways of oxidation and ketogenesis away from esterification, suggesting enhanced carnitine-dependent mitochondrial fatty acid uptake. The studies using octanoate indicated that norepinephrine also enhanced fatty acid oxidation by increasing the flux of acetyl-CoA through the Krebs cycle. The data suggest that stress-associated sympathetic activation and norepinephrine discharge, as observed in diabetic ketoacidosis, result in direct activation of ketogenesis in the liver.
Diabetes 1985 Aug
PMID:Effect of norepinephrine on ketogenesis, fatty acid oxidation, and esterification in isolated rat hepatocytes. 286 86


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