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

The discovery of a cold-labile cytosolic acetyl-CoA hydrolase of high activity in rat liver by Prass et al. [(1980) J. Biol. Chem. 255, 5215-5223] has questioned the importance of mitochondrial acetyl-CoA hydrolase for the formation of free acetate [Grigat et al. (1979) Biochem. J. 177, 71-79] under physiological conditions. Therefore this problem has been reevaluated by comparing various properties of the two enzymes. Cold-labile cytosolic acetyl-CoA hydrolase bands with an apparent Mr of 68000 during SDS/polyacrylamide gel electrophoresis, while the native enzyme elutes in two peaks with apparent Mr of 136000 and 245000 during gel chromatography in the presence of 2 mM ATP. The mitochondrial enzyme elutes under the same conditions with an apparent Mr of 157000. Under conditions where the cold-labile enzyme binds strongly to DEAE-Bio-Gel and ATP-agarose, the mitochondrial enzyme remains unbound. The cold-labile enzyme can be activated 14-fold by ATP, half-maximal activation occurring already at 40 microM ATP. AdoPP[NH]P, AdoPP[CH2]P and GTP have a similar though weaker effect. ADP as well as GDP can completely inhibit the cold-labile enzyme with 50% inhibition occurring for both nucleotides at about 1.45 microM. The binding of ATP and ADP is competitive. Acetyl phosphate and pyrophosphate have no effect on the activity of the cold-labile enzyme. The mitochondrial acetyl-CoA hydrolase is not affected by these nucleotides. CoASH is a strong product inhibitor (approximately equal to 80% inhibition at 40 microM CoASH) of the cold-labile enzyme, but only a weak inhibitor of the mitochondrial enzyme. Under in vivo conditions the activity of the cold-labile cytosolic acetyl-CoA hydrolase can be no more than 7% of the activity calculated for mitochondrial acetyl-CoA hydrolase under the same conditions. Accordingly the mitochondrial enzyme seems to be mainly responsible for the formation of free acetate by the intact liver, especially in view of the fact that the substrate specificity of the mitochondrial enzyme is much higher (activity ratios acetyl-CoA/butyryl-CoA 4.99 and 1.16 for the mitochondrial and the cold-labile enzyme respectively). Alloxan diabetes neither increased the activity of the cold-labile enzyme nor that of the mitochondrial enzyme. No experimental support has been found yet for the hypothesis that the acetyl-CoA hydrolase activity of the cold-labile enzyme represents the side-activity of an acetyl-transferase.
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PMID:On the regulation of cold-labile cytosolic and of mitochondrial acetyl-CoA hydrolase in rat liver. 285 46

These experiments were carried out to study the effects of acute cold exposure (0-2 degrees C/4 hr) on rectal temperature, blood glucose and plasma free fatty acids (FFA) in alloxan-diabetic rats. Male Wistar rats weighing 170-190 g were used and diabetes was induced by i.v. alloxan injection (40 mg/kg body wt). Cold exposure produced severe hypothermia in diabetic rats. After 4 hr of cold, blood glucose of diabetic rats was reduced from 296 +/- 16 to 86 +/- 12 mg/dl (P less than 0.01), and FFA increased slightly, but was not statistically different (P greater than 0.05) from the initial value. As expected, interscapular brown adipose tissue (IBAT) and retroperitoneal and epididymal white adipose tissues were significantly lower in diabetic than in control rats. Cold exposure reduced total IBAT lipids in control but not in diabetic animals. The results of this experiment suggest that diabetic rats were unable to maintain body temperature in the cold, probably because of a failure to generate an adequate amount of heat by nonshivering thermogenesis in brown adipose tissue.
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PMID:Effects of acute cold exposure on rectal temperature, blood glucose and plasma free fatty acids in alloxan-diabetic rats. 287 21

To investigate the effects of acclimation to a cold environment on the alteration of glucose and fat metabolism in diabetes, the levels of blood glucose, triacylglycerol, nonesterified fatty acid, and immunoreactive insulin were measured before and on the 3rd and 14th days after streptozotocin treatment in cold-acclimated (4 degrees C) and warm-acclimated (24 degrees C; control) rats. The cold-acclimated rats showed no hyperglycemia on the 14th day after streptozotocin treatment, whereas the control diabetic rats maintained high blood glucose levels. Triacylglycerol levels did not increase in the cold-acclimated diabetic rats, whereas the control diabetic rats showed markedly high triacylglycerol levels. Immunoreactive insulin levels remained constantly low in both cold-acclimated and control diabetic rats. It was concluded that acclimation to cold changed some of the metabolic consequences of diabetes caused by streptozotocin in rats.
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PMID:Streptozotocin diabetes in rats after acclimation to cold environment. 295 May 10

We have compared left ventricular function in 40 insulin-dependent diabetic patients (30 male, 10 female) aged 16-30 years (mean 23 years) with duration of diabetes 3 months to 25 years (mean 10 years) with 19 healthy age and sex-matched controls using radionuclide ventriculography at rest, during cold-pressor stimulation, isometric exercise, and dynamic exercise. There were no differences in exercise or smoking habits in the two groups. All subjects had a normal resting electrocardiogram and a normal electrocardiographic response to dynamic exercise using the Bruce protocol on the Marquette Computer Assisted System of Exercise. Left ventricular ejection fraction was similar at rest and fell in diabetics and controls, respectively, by 2.3 +/- 1.0% and 3.0 +/- 0.08% (NS) and by 2.4 +/- 0.8% and 2.2 +/- 0.8% (NS) during isometric exercise, and cold pressor testing. During supine dynamic exercise on a bicycle ergometer ejection fraction rose in both groups by 13.9 +/- 1.7% and 13.7 +/- 1.6%, respectively (NS). No statistically significant differences were found in peak ventricular filling and emptying rates and abnormalities of regional wall motion did not develop. Two female patients with diabetes for more than 10 years had an abnormal response to dynamic exercise manifested by a fall in ejection fraction. In comparison to the higher frequency of abnormalities reported in diabetics using echocardiography and the measurement of systolic time intervals, abnormal left ventricular function assessed by radionuclide ventriculography is uncommon in young patients.
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PMID:Cardiac function and insulin-dependent diabetes: radionuclide ventriculography in young diabetics. 295 Oct 77

In diabetes mellitus, polyneuropathy is an important complication and should be diagnosed as early as possible in order to prevent damage to the patient. Determination of warm, cold, and heat pain thresholds enables one to judge small nerve fiber sensitivity. This investigation was carried out to determine which parameters best predict such alterations. Using a "Marstock" Thermostimulator, 26 diabetics and 32 healthy subjects were stimulated behind both medial malleoli. At three different rates of temperature rise, repeated warm, cold, and heat pain threshold determinations were performed. The variability of intraindividual threshold ranges was noted. While heat pain determinations were not useful, determination of cold perception, at a moderate rate of temperature change, proved to be the most reliable indicator of small fiber lesions. Cold thresholds as well as their intraindividual ranges were most often impaired. The importance of this clinical investigatory method is discussed with respect to the importance of early prophylaxis of complications such as trophic lesions.
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PMID:Early diagnosis of diabetic small fiber neuropathy by disturbed cold perception. 296 56

Platelet and clotting abnormalities have been described in diabetes, but little is known about their relationship to daily stresses. In order to evaluate whether states of abnormal carbohydrate metabolism modify the hemostatic response to stress, 12 subjects with type I diabetes mellitus, 9 with type II, 7 with impaired glucose tolerance and 10 healthy controls were exposed to a cold pressor test. Plasma concentrations of beta-thromboglobulin (index of platelet activation) and of fibrinopeptide A (index of thrombin formation) were measured before and 15 minutes after forearm immersion in melting ice. Basal levels of both proteins were significantly elevated (p less than 0.02) in the combined group of patients with diabetes and impaired glucose tolerance. While in healthy controls cold exposure failed to modify plasma concentration of either protein, obvious changes occurred in the diabetic and impaired glucose tolerance groups. In the combined patients group, beta-thromboglobulin levels decreased from 1.37 +/- 0.44 nmol/l to 1.03 +/- 0.39 (mean +/- SD, p less than 0.01), after the cold test, possibly in consequence of enhanced vascular permeability; while fibrinopeptide A levels increased from 1.52 +/- 1.03 nmol/l to 3.45 +/- 4.19 (p less than 0.02). The degree and pattern of abnormalities observed in basal as well as stimulated levels of fibrinopeptide A differed somewhat among the three groups of patients. These studies indicate that, in the basal state, patients with diabetes or simple carbohydrate intolerance are more susceptible than controls to platelet activation and that after stress thrombin formation can occur although some variability exists among and within groups of patients. The consequences of such increased thrombotic activity may have a bearing on the pathogenesis of large vessel disease, a complication common to diabetes and impaired glucose tolerance.
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PMID:Platelet and clotting activities after cold stress in diabetic patients. 297 Jun 90

Cold stress produced a significant reduction in the concentration of immunoreactive beta-endorphin (IR-BE) in the anterior pituitary of diabetic female rats. IR-BE levels in the anterior pituitary of non-diabetic female rats were not affected by exposure to the cold. The effects of cold stress on IR-BE levels in the neurointermediate lobe of the pituitary and the hypothalamus were attenuated in diabetic as compared to control animals. These data suggest that in female rats, eight weeks of diabetes produced alterations in the neuroendocrine mechanisms which modulate IR-BE levels in the pituitary and hypothalamus in response to cold stress.
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PMID:Eight weeks of streptozotocin-induced diabetes influences the effects of cold stress on immunoreactive beta-endorphin levels in female rats. 297 9

Disturbed upper limb skin blood flow has been described in insulin-dependent (Type 1) diabetes mellitus, but the pathophysiological mechanism remains unclear. Hand skin blood flow was therefore measured at room temperature and following immersion of hands in cold and warm water in 13 healthy control subjects, in 10 patients with Type 1 diabetes mellitus and cardiovascular autonomic neuropathy, and a further 10 Type 1 diabetic patients with normal cardiovascular autonomic tone. Following cold challenge there was failure of digital artery clampdown in all diabetic patients in comparison with healthy control subjects (p less than 0.005), and the index finger temperature fell less (p less than 0.05). Laser Doppler flow was reduced at the palms at room temperature or following the warm challenge (p less than 0.008), as well as on the dorsum at room temperature (p less than 0.05), in all diabetic patients. In addition laser Doppler flow in the diabetic patients was reduced at the palms and dorsum immediately following cold water challenge (p less than 0.004) and this reduction persisted 15 min (p less than 0.05) and 30 min (p less than 0.01) into the recovery phase. In comparison to those diabetic patients with normal cardiovascular tone, those with cardiovascular autonomic neuropathy had reduced laser Doppler flow at the pulp 15 min after cold water immersion (p less than 0.05), at the nailbed immediately after cold water immersion (p less than 0.01), and at the palms immediately after warm water challenge (p less than 0.01).
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PMID:Altered hand skin blood flow in type 1 (insulin-dependent) diabetes mellitus. 297 48

Long-term cafeteria feeding, cold exposure, and the combination of treatments increased energy intake in female Wistar rats by 25%, 113%, and 150%, respectively, in comparison with controls (P less than 0.01). Although cafeteria feeding at room temperature markedly increased the insulin response to an intravenous glucose tolerance test (IVGTT), glucose tolerance was deteriorated (P less than 0.01). In contrast, cold exposure significantly improved glucose tolerance in the presence of a reduced insulin response in Purina- and cafeteria-fed animals. Moreover, cold exposure also decreased body weight gain and increased brown adipose tissue mass, total cytochrome-oxidase activity, and cellularity by approximately 600-800%. The results suggest that cold exposure enhances insulin sensitivity of peripheral tissues, whereas hyperphagia on a high-fat, low-protein diet leads to insulin resistance. In addition, the results demonstrate that prolonged stimulation of energy expenditure by cold exposure not only reverses the diabetogenic effects of cafeteria feeding but also improves glucose tolerance. This phenomenon could result from a combination of two factors: (1) a cold-induced prevention of obesity; and (2) an enhanced disposal of circulating glucose into peripheral tissues, including brown adipose tissue.
Diabetes 1986 Mar
PMID:Cold exposure reverses the diabetogenic effects of high-fat feeding. 300 94

Although whole-body leucine flux is widely measured to study body protein turnover in humans, the contribution of specific tissues to the total-body measurement remains unknown. By combining the organ-balance technique with the systemic infusion of L-[1-14C]leucine, we quantitated leucine production and disposal by splanchnic and leg tissues and by the whole body, simultaneously, in six normal men before and during amino acid infusion. At steady state, disposal of arterial leucine by splanchnic and leg tissues was calculated from the percent extraction (E) of L-[1-14C]leucine counts: uptake = E x [Leu]a x flow. Tissue release of cold leucine (from protein turnover) into vein was calculated as the difference between leucine uptake and the net tissue leucine balance. In the postabsorptive state, despite substantial (P less than .01) extraction of L-[1-14C]leucine by splanchnic (23 +/- 1%) and leg (18 +/- 2%) tissues, net leucine balance across both tissue beds was small, indicating active simultaneous disposal and production of leucine at nearly equivalent rates. Splanchnic tissues accounted for approximately 50% of the measured total-body leucine flux. During amino acid infusion, the net leucine balance across splanchnic and leg tissues became positive, reflecting not only an increase in leucine uptake but also a marked suppression (by approximately 50%, P less than .02) of cold leucine release. This reduction in splanchnic and leg leucine release was indicated by a sharp decline in whole-body endogenous leucine flux.(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes 1988 Oct
PMID:Measurement of L-[1-14C]leucine kinetics in splanchnic and leg tissues in humans. Effect of amino acid infusion. 304 68


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