Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In order to obtain some information about the role of cAMP in the regulation of cell turnover of the intestinal mucosa it was interesting to investigate whether chronic pharmacologically induced changes in the cellular cAMP levels could cause alterations in mucosal growth in the case of a well defined animal modell, involving increased cell proliferation rate, such as chronic experimental diabetes mellitus of the rat. Since it has been suggested that cAMP levels on the one hand are low in cell division and increased cAMP levels on the other hand inhibit cell division, the aim of the study was to induce a suppression of the cell proliferation rate in the intestinal mucosa by chronic theophyllin application, a well known PDE-inhibitor. The following results could be obtained: Chronic theophyllin application induces a hyperplastic alteration of the small intestinal mucosa of the rat, which is similar to that observed in diabetes mellitus. In diabetic animals theophyllin causes a further increase in hyperplasia. The morphological alterations of the intestinal mucosa are more pronounced than the functional changes. In experimental diabetes mellitus the radioimmunologically determined cAMP level in the intestinal mucosa is rather low. Chronic theophyllin application alone or in combination with experimental diabetes mellitus was unable to increase the cAMP-level continuously. This could be a result of an adaptive change of the cAMP regulating enzyme system. Therefore theophyllin induced mucosal alterations are probably due to systemic effects of this drug.
 ...
PMID:[The effect of theophyllin on small intestinal structure and function of the diabetic rat (author's transl)]. 22 97

To gain information on the manner in which insulin suppresses lipolysis in man, isolated adipocytes, prepared from subcutaneous adipose tissue, were incubated with insulin (100 microunits/ml) alone and in combination with isoproterenol (10(-7) M or 10(-8) M). Cyclic AMP concentration was measured at 60 min; glycerol release, used as an index of lipolysis, was determined at 45 and 75 min. Insulin consistently reduced both basal and stimulated cyclic AMP and glycerol release: the degree of suppression of each was comparable. In subsequent experiments, the ability of insulin to suppress glycerol release stimulated by isoproterenol, theophylline, and dibutyryl cyclic AMP (dbcAMP), respectively, was compared. Insulin substantially reduced the raised levels of cyclic AMP and glycerol release prompted by isoproterenol and theophylline, but it had little effect on increases caused by dbcAMP. These findings support the view that reduction in cyclic AMP is an important component in the regulation of fat mobilization by insulin.
Diabetes 1979 Nov
PMID:Insulin inhibition of lipolysis of human adipocytes: the role of cyclic adenosine monophosphate. 22 42

Currently used methods for plasma cAMP measurements are either tedious (chromatographic preparation of sample) or potentially inaccurate (direct assay of plasma samples). A rapid, simple, and accurate competitive binding assay for plasma cAMP, which does not require chromatographic preparation of the sample, has been developed. This procedure prevents destruction of plasma cAMP by utilizing both theophylline and EDTA in the collection of the blood sample. Human plasma contains variable amounts of cAMP-binding activity which interfere with the measurement of cAMP by the standard competitive binding assay. Our assay procedure removes this binding activity by precipitation of plasma proteins with perchloric acid. The normal fasting value (+/- SD) of plasma cAMP using this technique is 17.6 +/- 4.3 pmol/ml, which is identical to values obtained by methods utilizing chromatographic purification of samples (18.3 +/- 3.0). The fasting plasma cAMP of patients with hyperparathyroidism is normal (16.2 +/- 3.4), but patients with maturity-onset diabetes mellitus have fasting values significantly below normal (12.3 +/- 2.4).
 ...
PMID:Measurement of plasma adenosine 3',5'-monophosphate. 23 35

Obesity in the Zucker rat is accompanied by hyperlipemia, hyperinsulinism, insulin resistance, pancreatic hyperplasia, and islet hypertrophy. This study correlates the morphologic heterogeneity of isolated pancreatic islets with secretion of insulin and glucagon in the perifusion system. Islet size was arbitrarily defined as large (greater than 0.45 mm) or small (smaller than 0.12 mm). Protein content and volume (V = 4/3pir3) were calculated for groups and individual islets, respectively. Islets from obese rats secreted more insulin in response to glucose and aminophylline than islets from lean rats (peak 7.8 +/- 2.4 vs. 1.5 +/- 0.37 microU/islet/min, P less than 0.005). Insulin release was related directly to islet size and protein content. Small islets from lean and obese animals produced less insulin per islet than large islets (P less than 0.005). In terms of islet volume, however, large islets were inefficient insulin releasers as compared to small islets (P less than 0.005). Stimulation with Br-cAMP released glucagon from islets of lean but not from large islets of obese animals (peak 11 +/- 3.3 vs. 4.1 +/- 0.3 pg/microgram protein per minute, P less than 0.05). Arginine produced the same effect on glucagon release (P less than 0.05) as stimulation with Br-cAMP. The observed increased insulin release rates and the blunted glucagon response are related to islet size in the pancreas of the Zucker rat.
Diabetes 1979 Jun
PMID:Correlation between morphology and function in isolated islets of the Zucker rat. 37 79

1. Regulation of gluconeogenic substrate supply and modulation of the gluconeogenic pathway in the liver are both important in the control of gluconeogenesis by glucocorticoids. 2. Adrenal deficiency decreases the release of gluconeogenic and other amino acids from skeletal muscle during starvation. The effect is reversed by glucocorticoid replacement. The changes in amino acid release are accompanied by similar alterations in tissue amino acid levels and are not explained by alterations in net protein breakdown. Glucocorticoids do not alter protein catabolism and cause a small inhibition of protein synthesis. The biochemical alterations underlying the changes in amino acid metabolism induced by these steroids remain to be elucidated. Glucocorticoids may also regulate the supply of gluconeogenic substrates through permissive effects on the lipolytic action of catecholamines and other hormones in adipose tissue and on the glycogenolytic action of catecholamines on skeletal muscle. 3. Glucocorticoids are required for the increases in gluconeogenesis in starvation and diabetes. Part of their action is exerted directly on the liver and appears to involve modulation of P-enlopyruvate carboxykinase levels. Glucocorticoids increase the synthesis of this enzyme apparently through effects at the level of transcription. 4. Glucocorticoids exert permissive effects on the stimulation of gluconeogenesis in the liver by glucagon and epinephrine. The steroids are not required for cAMP generation or protein kinase activation by these hormones, but appear to act by maintaining the responsiveness of certain enzymes to the effects of the cAMP and alpha-adrenergic systems. It is proposed that this involves the maintenance of a normal intracellular ionic environment.
 ...
PMID:Regulation of gluconeogenesis by glucocorticoids. 38 91

The infrequency of diabetes mellitus and asthma in the same individual is re-examined. The antagonism between epinephrine and insulin, as suggested by Konig in 1935, is indeed accurate. The assays done by the Eli Lilly Research Department revealed no in vitro effect of insulin on the CAMP and GMP level of mast cells as occurs in liver cells. It is felt that this effect is probably an in vivo effect produced via the vagus nerve and alpha-adrenergic receptor system stimulation. This would explain the mechanism of aggravation of asthma by excess insulin. Dr. Petersen's studies, the negative intradermal skin tests to insulin and the absence of change on either beef or pork insulin usage by our patient all point to a nonatopic factor in the aggravation of the asthma of this patient. In the uncommon occurrence of asthma and diabetes in the same patient, insulin dosage should be considered as a factor in all such asthmatics who do not respond well to conventional therapy. Two additional asthmatics who also have diabetes did improve with cessation of nocturnal asthma by a reduction of their evening dose of insulin. A high fat, low carbohydrate diet, as suggested by Abrahamson to avoid dietary hyperinsulinism, is certainly worth considering in patients with nocturnal asthma. If patients cannot be made to follow a diet requiring frequent feedings high in protein and fats and low in carbohydrates, another approach suggests itself. Abrahamson was able to relieve the patients who developed nocturnal asthma with hypoglycemia by having them drink a glass of milk. Assuming other causes have been eliminated and a patient awakens each day at 3:00 a.m., an alarm clock could be set at 2:00 a.m. Milk or a milk substitute in milk sensitive patients could be taken at 2:00 a.m. to raise the blood sugar and hopefully prevent the asthma associated with hypoglycemia. Also to be noted is the ubiquitous use of tartrazine in so many drugs, including those used to relieve asthmatic symptoms. Inasmuch as tartrazine so frequently aggravates the aspirin sensitive asthmatic, it would be wise for pharmaceutical companies to become cognizant of this fact and delete tartrazine from their antiasthmatic preparations.
 ...
PMID:Diabetes mellitus and insulin in an aspirin sensitive asthmatic. 125 4

PGE1 has been found to improve the symptoms of diabetic neuropathy. We considered that a PGI2 derivative may also have a similar action and therefore studied its effect in diabetic rats. Iloprost was administered intraperitoneally to streptozotocin-induced diabetic rats at a dose of 10 micrograms/kg/day for a month. The changes in nerve conduction velocity (NCV) were measured in the tail. One day after the last dose of iloprost, both sciatic nerves were removed from each rat, homogenized, and extracted with 6% TCA. The sorbitol and myo-inositol concentrations were determined by a combination of HPLC and an enzymatic method. Cyclic AMP (cAMP) levels were determined by RIA, and Na+, K+ ATPase activity was assessed by the enzyme cycling method of Greene and Lattimer. Iloprost was found to improve the NCV in the diabetic rats. The sorbitol content was not affected by iloprost, but the myo-inositol content was higher in the iloprost group than in the untreated group, although the difference was not statistically significant. The Na+, K+ ATPase activity and cAMP content were significantly higher in the iloprost group than in the untreated group. These findings suggest the possibility that the cAMP-dependent protein kinase (A-kinase) system has an important influence on improvement in Na+, K+ ATPase activity.
Diabetes Res Clin Pract 1992 Nov
PMID:Effect of a prostaglandin I2 derivative (iloprost) on peripheral neuropathy of diabetic rats. 128 52

Magnesium is an essential cofactor for many enzymatic reactions, especially those involved in energy metabolism. Deficits of magnesium are prevalent due to inadequate intake or malabsorption and due to the renal loss of magnesium that occurs in certain disease states (alcoholism, diabetes) and with drug therapy (diuretics, aminoglycosides, cisplatin, digoxin, cyclosporin, amphotericin B). Protracted deficits of magnesium in humans and animals result in neurological disturbances, including hyperexcitability, convulsions and various psychiatric symptoms ranging from apathy to psychosis, some of which can be reversed with magnesium supplementation, others requiring correction of the dysregulation mechanism. Although the role of magnesium in neuronal function is not completely understood, a lowering of CSF or brain magnesium can induce epileptiform activity and there is an association between decreased CSF magnesium and the development of seizures. CSF concentrations of magnesium are normally higher than magnesium plasma ultrafiltrate (diffusible) concentrations due to the active transport of magnesium across the blood-brain barrier. Under conditions of magnesium deficiency, CSF concentrations decline, although this decline lags behind and is less pronounced than the changes observed in plasma magnesium concentrations. Decreases in CSF magnesium concentrations correlate with the alterations observed in extracellular brain magnesium concentrations in animals following the dietary deprivation of magnesium. CSF magnesium concentrations can readily be repleted following magnesium supplementation, although high dose magnesium therapy, such as that used in the treatment of convulsions in eclampsia, will only increase CSF magnesium concentrations to a very limited degree (approximately 11-18 per cent) above physiological concentrations. Greater increases in CSF magnesium may occur in neonates since neonatal swine, following treatment with magnesium, have CSF magnesium concentrations that are similar to their plasma concentrations. There has been a recent resurgence of interest in magnesium deficiency and its neurological consequences due to the finding that magnesium, at physiological concentrations, blocks N-methyl-D-aspartate (NMDA) receptors in neurones. NMDA receptors are normally activated by glutamate and/or aspartate which represent the principal neurotransmitters for excitatory synaptic transmission in vertebrate CNS. Magnesium deficiency produces epileptiform activity in the CNS which can be blocked by NMDA receptor antagonists. Other mechanisms, including alterations in Na+/K(+)-ATPase activity, cAMP/cGMP concentrations and calcium currents in pre- and postsynaptic membranes, may also be at least partially responsible for the neuronal effects associated with low brain magnesium. Further studies are necessary to increase our understanding of the neurological implications of magnesium deficit in the central nervous system.
 ...
PMID:Brain and CSF magnesium concentrations during magnesium deficit in animals and humans: neurological symptoms. 129 67

The purpose of the study was to determine the physiological actions of amylin, a novel 37-amino acid peptide isolated from pancreatic islet amyloid deposits. Our results showed that an infusion of amylin reduced fasting plasma insulin levels and impaired glucose tolerance in mice. Amylin significantly reduced insulin secretion in rat insulinoma cell lines (Rin m5F cells) that were stimulated by either isoproterenol and forskolin, but it did not affect insulin secretion stimulated by isobutyl-methylxanthine (IBMX) or dibutyryl cyclic-adenosine monophosphate (db-cAMP). Amylin also reduced cAMP levels in Rin m5F cells in response to isoproterenol, but did not affect cAMP levels in cells pretreated with pertussis toxin. These results suggest that the reduction of cAMP by amylin may be mediated through pertussis toxin-sensitive Gi proteins. Amylin significantly reduced basal and insulin-stimulated glycogen synthesis in rat primary cultured hepatocytes. Amylin stimulated basal and insulin-stimulated lipogenesis in hepatocytes. Amylin did not affect DNA synthesis in hepatocytes. These results suggest that amylin conducts dispersion actions on in vivo glucose metabolism in rat, and in vitro insulin secretion from Rin m5F cells and metabolism in rat hepatocytes.
Diabetes Res Clin Pract 1992 Jan
PMID:The effects of amylin on insulin secretion from Rin m5F cells and glycogen synthesis and lipogenesis in rat primary cultured hepatocytes. 131 71

1. The effect of administration of the angiotensin converting enzyme inhibitor (ACEI), lisinopril (Carace; 10-40 mg twice daily) and the calcium channel blocker, nifedipine (Adalat Retard; 20-40 mg twice daily) on ex vivo [45Ca2+] uptake by platelets from hypertensive diabetic (type 1 and 2) patients was investigated. 2. At the end of at least 3 months treatment, blood was collected prior to the patient taking the morning dose of medication and washed platelets prepared. [45Ca2+] uptake was monitored following the addition of adrenaline, isoprenaline and dibutyryl cAMP (dbcAMP), as well as in unstimulated (zero) platelets. 3. Both nifedipine and lisinopril significantly inhibited the ex vivo uptake of [45Ca2+] by platelets when this process was stimulated by adrenaline, isoprenaline and dibutyryl cAMP. Basal uptake was also inhibited in both groups. 4. These data consolidate the hypothesis that ACE inhibitors may possess calcium channel/calcium mobilisation blocking properties. Apart from its hypertensive action, lisinopril may also reduce platelet activity via modulation of calcium dynamics, thereby reducing the incidence of vascular complications associated with diabetes mellitus.
 ...
PMID:Lisinopril and nifedipine administration inhibits the ex vivo uptake of [45Ca2+] by platelets from hypertensive diabetic patients. 131 54


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>