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

The changes in neuronal Ca2+ homeostasis were studied on dorsal horn neurons from spinal cord rat slices and freshly isolated dorsal root ganglion neurons of mice in control condition and under streptozotocin (STZ)-induced diabetes. The cytoplasmic free Ca2+ concentration ([Ca2+]i) was measured using fura-2 and indo-1 based microfluorimetry. The recovery of depolarization-induced [Ca2+]i increase was delayed in diabetic neurons compared with normal animals. The amplitude of calcium release from caffeine-sensitive endoplasmic reticulum calcium stores became significantly smaller in diabetic neurons. The participation of mitochondria in [Ca2+]i homeostasis was determined by investigation of changes which occurred after addition of mitochondrial protonophore (CCCP) to the extracellular solution. In control cells 10 (M CCCP applied before membrane depolarization induced an increase of the amplitude of depolarization-induced [Ca2+]i transients and disappearance of their delayed recovery, indicating the participation of mitochondria in fast uptake of Ca2+ ions from the cytosol during the peak of the transient and subsequent slow release them back during its decay. In neurons from diabetic animals the increase of the peak transient amplitude under the action of CCCP became diminished, and the delayed elevation of [Ca2+]i disappeared in small size neurons. We conclude that streptozotocin-induced diabetes is associated with prominent changes in the mechanisms responsible for [Ca2+]i regulation in neurones of the nociceptive system, which presumably include a slow down of Ca2+ elimination from the cytoplasm by endoplasmic reticulum and mitochondria.
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PMID:[Changes in calcium signaling in mammalian nociceptive neurons in diabetes mellitus]. 1047 2

Intracellular calcium signalling was studied in the dorsal horn from neurons of rats with streptozotocin-induced diabetes versus control animals. The cytoplasmic Ca2+ concentration ([Ca2+]i) was measured in Fura-2 acetoxymethyl ester-loaded dorsal horn neurons from acutely isolated spinal cord slices using a fluorescence technique. The recovery of depolarization-induced [Ca2+]i increase was delayed in diabetic neurons compared with normal animals. In normal neurons, [Ca2+]i after the end of KCl depolarization recovered to the basal level monoexponentially with a time constant of 8.0+/-0.5 s (n = 23), while diabetic neurons showed two exponentials in the [Ca2+]i recovery. The time constants of these exponentials were 7.2+/-0.5 and 23.0+/-0.6 s (n = 19), respectively. The amplitude of calcium release from caffeine-sensitive endoplasmic reticulum calcium stores became significantly smaller in diabetic neurons. The amplitudes of [Ca2+]i transients evoked by 30 mM caffeine were 268+/-29 nM (n = 13) and 31+/-9 nM (n = 17) in control and diabetic neurons, respectively. We conclude that streptozotocin-induced diabetes is associated with prominent changes in the mechanisms responsible for [Ca2+]i regulation, which presumably include a slowdown of Ca2+ elimination from the cytoplasm by the endoplasmic reticulum.
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PMID:Changes in calcium signalling in dorsal horn neurons in rats with streptozotocin-induced diabetes. 1057 79

Repaglinide is a novel insulin secretagogue developed in response to the need for a fast-acting, oral prandial glucose regulator for the treatment of type 2 (non-insulin-dependent) diabetes mellitus. Repaglinide is metabolized mainly in the liver; its pharmacokinetics may therefore be altered by hepatic dysfunction. This open, parallel-group study compared the pharmacokinetics and tolerability of a single 4 mg dose of repaglinide in healthy subjects (n = 12) and patients with chronic liver disease (CLD) (n = 12). Values for AUC and Cmax were significantly higher in CLD patients compared with healthy subjects, and the MRT was prolonged in CLD patients. Values for tmax did not differ between the groups, but t1/2 was significantly prolonged in CLD patients compared with previously determined values in healthy subjects. AUC was inversely correlated with caffeine clearance in CLD patients but not in healthy subjects. Blood glucose profiles were similar in both groups. Adverse events (principally hypoglycemia) were similar in the two groups; none was serious. Repaglinide clearance is significantly reduced in patients with hepatic impairment; the agent should be used with caution in this group.
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PMID:Single-dose pharmacokinetics of repaglinide in subjects with chronic liver disease. 1066 20

Restless legs syndrome (RLS) is a perplexing, debilitating, and fairly common condition that can be challenging to manage. Hallmark symptoms include an increase in the severity of sensations during rest and an irresistible urge to move the affected limbs. RLS often occurs concomitantly with periodic limb movement disorder. There are no known causes of RLS, but likely triggers include heredity, iron and vitamin deficiencies, caffeine, and alcohol. Chronic conditions such as diabetes, peripheral neuropathy, and Parkinson's disease can worsen and prolong RLS symptoms. Symptom management begins by establishing proper nutrition intake and improved sleep hygiene. If these fail, conservative pharmacologic treatment is appropriate, with regimens chosen from dopaminergic agents, benzodiazepines, opioids, and anticonvulsants.
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PMID:Restless legs syndrome. How to provide symptom relief with drug and nondrug therapies. 1077 1

We examined the involvement of cytosolic calcium in the modulation of the formalin-induced nociceptive response by diabetes. Injection of formalin into the hindpaw of mice produced a biphasic nociceptive response consisting of immediate (first phase) and tonic (second phase) components. Although the duration of the first-phase response was significantly longer in diabetic mice than in non-diabetic mice, the second phase was significantly shorter in diabetic mice. The first-phase response was dose-dependently and significantly reduced by pretreatment with ryanodine, which blocks Ca(2+) release from Ca(2+)/caffeine-sensitive microsomal pools. The second-phase response was also significantly increased when diabetic mice were pretreated with ryanodine. However, ryanodine had no significant effect on either the first-phase or second-phase response in non-diabetic mice. On the other hand, pretreatment with thapsigargin, which inhibits Ca(2+) uptake into the inositol-1,4, 5-trisphosphate-sensitive microsomal Ca(2+) pool, significantly enhanced the first-phase response in non-diabetic mice. Furthermore, thapsigargin significantly and dose-dependently reduced the second phase of the formalin-induced nociceptive response in non-diabetic mice. Thapsigargin administered i.t. did not significantly affect either the first- or the second-phase response in diabetic mice. These results suggest that the change in the formalin-induced nociceptive response in diabetic mice may be due, at least in part, to the modification of nociceptive transmission in the spinal cord by intracellular calcium.
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PMID:Modulation of the formalin-induced nociceptive response by diabetes: possible involvement of intracellular calcium. 1079 95

The effects of 1,4-dideoxy-1,4-imino-d-arabinitol (DAB) were investigated on preparations of glycogen phosphorylase (GP) and in C57BL6J (ob/ob) mice by (13)C NMR in vivo. Independent of the phosphorylation state or the mammalian species or tissue from which GP was derived, DAB inhibited GP with K(i)-values of approximately 400 nM. The mode of inhibition was uncompetitive or noncompetitive, with respect to glycogen and P(i), respectively. The effects of glucose and caffeine on the inhibitory effect of DAB were investigated. Taken together, these data suggest that DAB defines a novel mechanism of action. Intraperitoneal treatment with DAB (a total of 105 mg/kg in seven doses) for 210 min inhibited glucagon-stimulated glycogenolysis in obese and lean mice. Thus, liver glycogen levels were 361 +/- 19 and 228 +/- 19 micromol glucosyl units/g with DAB plus glucagon in lean and obese mice, respectively, compared to 115 +/- 24 and 37 +/- 8 micromol glucosyl units/g liver with glucagon only. Moreover, with glucagon only end-point blood glucose levels were at 29 +/- 2 and 17.5 +/- 2 mM in obese and lean mice, respectively, compared to 17.5 +/- 1 and 12 +/- 1 mM with glucagon plus DAB. In conclusion, DAB is a novel and potent inhibitor of GP with an apparently distinct mechanism of action. Further, DAB inhibited the hepatic glycogen breakdown in vivo and displayed an accompanying anti-hyperglycemic effect, which was most pronounced in obese mice. The data suggest that inhibition of GP may offer a therapeutic principle in Type 2 diabetes.
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PMID:Kinetic and functional characterization of 1,4-dideoxy-1, 4-imino-d-arabinitol: a potent inhibitor of glycogen phosphorylase with anti-hyperglyceamic effect in ob/ob mice. 1093 82

A 67-year-old man, complicated with liver cirrhosis, diabetes mellitus, and ischemic heart disease, was scheduled for gastrectomy. He had been taking an over-the-counter (OTC) analgesic containing acetaminophen, ethenzamid and caffeine for 20 years, and refused to stop taking it preoperatively. He received general anesthesia with isoflurane, supplemented with fentanyl and midazolam. Muscle relaxation was obtained with vecuronium. Isosorbide was infused continuously to prevent myocardial ischemia. The anesthetic course was uneventful. Postoperatively, the patient experienced no difficulty in abstaining from taking the OTC analgesic. The patient's perioperative course indicates that he was not dependent on this OTC drug, but he needed this medication only to ameliorate his preoperative anxiety or depressive mood.
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PMID:[Perioperative management of a patient with a history of over-the-counter analgesic abuse for 20 years]. 1099 90

In reviewing the epidemiology of recurrent abortion (RAB), we believe it is necessary to consider the epidemiology of spontaneous abortion (SAB) as well, since it is clear that even a single pregnancy loss increases the risk for a subsequent abortion. In addition, any attempt to identify epidemiologic risk factors for SAB or RAB must deal with the fact that at least 50% of SABs are associated with genetic abnormalities. Given that most epidemiologic studies have not distinguished karyotypically abnormal abortuses, risk factors are likely to be underestimated. Nevertheless, there is fair agreement that a variety of factors may increase risk for SAB or RAB, including advanced maternal age, single gene mutations such as PKU or G6PD deficiency, structural abnormalities of the uterus, poorly controlled diabetes, antiphospholipid syndrome, and smoking. More controversial is the role of luteal phase defect or hyperandrogenism, alloimmune factors, genital infections, caffeine or alcohol use, and trace element or chemical exposure from tap water or in the workplace. Besides better designed epidemiologic studies to detect modifiable risk factors for SAB or RAB, there is a clear need for clinical trials of therapy for RAB which meet minimum epidemiologic standards including randomization, double-blinded (when possible), and placebo-controlled (when ethical).
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PMID:The epidemiology of recurrent pregnancy loss. 1135 91

Caffeine, 1,3,7trimethylxanthine, is used by 80% of the adult population of the world in its various forms. Even the simple pleasure of consuming this socially acceptable drug has implications for the person with diabetes mellitus. Caffeine may increase an individual's sensitivity to hypoglycemia through the combined effects of reducing substrate delivery to the brain via constriction of the cerebral arteries, whilst simultaneously increasing brain glucose metabolism and augmenting catecholamine production. This article summarizes the evidence supporting the hypothesis that caffeine influences the perception of and physiological response to hypoglycemia. Under laboratory conditions, acute ingestion of caffeine markedly enhances the symptomatic and sympathoadrenal responses to hypoglycemia in both healthy volunteers and patients with type 1 diabetes. Recently a study of free-living people with type 1 diabetes showed that caffeine consumption increased the awareness of hypoglycemia. Caffeine has been associated with a number of negative effects and addiction. Most serious of these associations are ischemic heart disease and hypertension, the relationships have not been clearly established and the evidence to date is controversial. Thus we conclude that in modest doses, caffeine may be a useful adjuvant therapy for patients with hypoglycemia unawareness. For once here is a therapy which is inexpensive, safe, and remarkably popular with its consumers.
Diabetes Technol Ther 1999
PMID:The best defense against hypoglycemia is to recognize it: is caffeine useful? 1147 92

Foetal and neonatal brain is under the influence of environmental factors from maternal and extra-maternal origin. Based on the available data, these environmental factors can be classified into three arbitrary groups: (i) factors and maternal status with a demonstrated deleterious effect on the foetal brain (i.e. ethanol, cocaine, some drugs including anticonvulsants, some viral infections, maternal diabetes, untreated maternal phenylketonuria); (ii) factors highly suspected to interfere with foetal brain development (i.e. lead and other heavy metals, some drugs like benzodiazepines, nicotine); (iii) factors which have been shown to be safe for the developing brain in the available studies (i.e. low to moderate doses of caffeine, methadone). However, most of these studies do not address the potential risk of environmental factors on minimal to moderate cognitive and behavioural disturbances. Finally, the impact of the neonatal environment on brain development in very pre-term infants is probably underestimated.
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PMID:Environmental factors and disturbances of brain development. 1148 23


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