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

To determine the nature of the pancreatic islet cell cholecystokinin (CCK) receptor, we studied CCK receptor binding and biologic activity in isolated rat pancreatic islets. Binding of 70 pM 125I-CCK to collagenase-prepared isolated rat pancreatic islets at 24 degrees C was one-half maximal after 5 min and maximal at 60 min. At 60 min, specific binding was 12% of total radioactivity per 100 micrograms islet protein; nonspecific binding (in the presence of 1 microM CCK 8) was less than 2% of total radioactivity. Unlabeled CCK 33 inhibited labeled hormone binding one-half maximally at 2 nM; Scatchard analysis showed one binding site (Kd, 2.3 +/- 0.4 nM; Bmax, 8.1 pmol/mg protein). The agonist selectivity of this binding site was: CCK 8 = CCK 33 greater than desulfated-CCK 8 greater than CCK 4. Two CCK antagonists were studied; N-carbobenzoxy-L-tryptophan was more potent than dibutyryl-cGMP. When the effect of CCK on insulin release from the islets was studied, the order of potency of CCK agonists and antagonists on insulin secretion was the same as the order of their ability to inhibit 125I-CCK binding. The effect of CCK on insulin secretion was dependent on the glucose concentration in the media. CCK had no effect at 5.6 mM glucose and was fully effective at 11.0 mM glucose. These data, therefore, indicate that: specific binding sites for CCK are present in rat pancreatic beta cells; and CCK acts in concert with glucose to stimulate insulin secretion.
Diabetes 1986 Jan
PMID:Evidence that cholecystokinin interacts with specific receptors and regulates insulin release in isolated rat islets of Langerhans. 300 Aug 56

Monosaccharide autoxidation (a transition metal-catalysed process that generates H2O2 and ketoaldehydes) appears to contribute to protein modification by glucose in vitro. The metal-chelating agent diethylenetriaminepenta-acetic acid (DETAPAC), which inhibits glucose autoxidation, also reduces the covalent attachment of glucose to bovine serum albumin. A maximal 45% inhibition of covalent attachment was observed, but this varied with glucose and DETAPAC concentrations in a complex fashion, suggesting at least two modes of attachment. The extent of inhibition of the metal-catalysed pathway correlated with the extent of inhibition of glycosylation-associated chromo- and fluorophore development. DETAPAC also inhibited tryptophan fluorescence quenching associated with glycosylation. Conversely, ketoaldehydes analogous to those produced by glucose autoxidation, but generated by 60Co irradiation, bound avidly to albumin and accelerated browning reactions. It is therefore suggested that a component of protein glycosylation is dependent upon glucose autoxidation and subsequent covalent attachment of ketoaldehydes. The process of glucose autoxidation, or ketoaldehydes derived therefrom, appear to be important in chromophoric and fluorophoric alterations. It is noted, consistent with these observations, that the chemical evidence for the currently accepted 'Amadori' product derived from the reaction of glucose with protein amino groups is consistent also with the structure expected for the attachment of a glucose-derived ketoaldehyde to protein. The concept of 'autoxidative glycosylation' is briefly discussed in relation to oxidative stress in diabetes mellitus.
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PMID:Glucose autoxidation and protein modification. The potential role of 'autoxidative glycosylation' in diabetes. 311 42

The structural peculiarities of rabbit muscle aldolase accompanying enhancement of the aldolase activity in diabetes are described from the data of tryptophan phosphorescence at the room temperature and fluorescence polarization. It is shown that the pathology-concomitant conformational changes occur in both the hydrophobic part and NAD-binding site of the enzyme. The character of the structural changes in the hydrophobic part of the protein in diabetes and an increase in the enzymic activity are similar to that observed in normal aldolase after its interaction with NADH and are believed to be associated with the enhancement of the rigidity in the Trp-147 environment.
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PMID:[Structuro-functional characteristics of aldolase from rabbit muscles in diabetes]. 318 55

Serotonin metabolism was studied in several brain regions of control and Streptozotocin-treated male Wistar rats. After induction of diabetes, the animals were killed at 24 hours. Concentrations of brain tryptophan show a generalized increase in all brain regions, being only significant in medulla-pons. Serotonin levels do not change, while 5-HIAA concentrations, as well as the ratio 5-HIAA/5-HT, show significant increases in medulla-pons and mid-brain.
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PMID:Effects of short term experimental diabetes on brain serotonin metabolism. 323 81

Food intake regulation is influenced by serum amino acid (AA) ratios. The objectives of this study were to determine whether non-obese subjects with diabetes have normal serum AA ratios, and to see if AA ratios relate to perceived hunger. We therefore measured fasting serum AA in nine normal subjects on two occasions and 19 patients with diabetes on four occasions over a two month period. At the time of the blood samples, the subjects with diabetes were asked to rate how hungry they felt on a scale of -3 (very hungry) to +3 (very full). There were no significant differences between the mean AA ratios of normal and diabetic subjects. There was a positive correlation between reported hunger score and the ratio of serum tryptophan (TRP) to the sum of the concentrations of the other large neutral AA (LNAA) (r = 0.286, n = 78, p less than 0.05). The relationships between hunger and other AA ratios were not significant. Variations of the TRP/LNAA ratio within each subject did not relate to differences in hunger from day-to-day. However, there was a positive correlation between the mean TRP/LNAA ratio and mean hunger score of the different subjects (r = 0.495, n = 19, p less than 0.05). The relationships between TRP/LNAA ratio and body weight or hunger score were not significant. It is concluded that the serum AA ratios are normal in patients with diabetes. The data is consistent with the hypothesis that a low serum TRP/LNAA ratio causes increased feelings of hunger in different individuals.
Diabetes Res 1988 Nov
PMID:Relationship between fasting serum tryptophan/large neutral amino acid ratio and reported hunger in subjects with diabetes. 324 45

In vivo voltammetry was used to measure the synaptic release of rat striatal dopamine and serotonin after the administration of the amino acid L-tryptophan to streptozocin-induced diabetic rats. Dopamine and serotonin release from rat striatum was studied at a short-term or acute (3-day) interval and a long-term or chronic (3- to 7-wk) interval after the induction of diabetes. The study was also done in age-, sex-, and food-matched controls. The findings show that L-tryptophan decreased dopamine release from rat striatum in nondiabetic rats. The decreased striatal dopamine release, after L-tryptophan administration, was exacerbated in acutely diabetic rats and further exacerbated in chronically diabetic rats. By contrast, rat striatal serotonin release predictably increased after L-tryptophan injection in nondiabetic rats. A further increased striatal serotonin release was seen in acutely diabetic rats. Chronically diabetic rats, however, responded to L-tryptophan with a dramatic and significant decrease in striatal serotonin release. The results show that in acutely diabetic and normal rats, L-tryptophan administration reduced striatal dopamine and increased striatal serotonin release, whereas in chronically diabetic rats, the release of both biogenic amines was decreased. The findings indicate that the progression of diabetes is associated with an impaired ability to release primary neurotransmitter biogenic amines.
Diabetes 1988 Jul
PMID:Diabetes-related changes in L-tryptophan-induced release of striatal biogenic amines. 338 90

A new beta-chain hemoglobin variant, Hb Randwick [beta 15(A12)Trp----Gly] was detected in a 43-year-old female of Northern Italian parentage. During investigation for possible diabetes, mild red cell changes were noted and hemoglobin electrophoresis studies were requested. Independently, her sister's assessment had resulted in similar investigations. The most prominent findings were numerous "Hb H"-like inclusions and a positive isopropanol stability test. The hemoglobin variant separated poorly towards the anode at pH 9.2 and the level was estimated to be between 48-50% of the total hemoglobin. The variant beta-chain was partially purified by column chromatography, and its tryptic peptides fractionated by high performance liquid chromatography. Amino acid analysis and sequence data indicated that the tryptophan at residue 15 (A12) had been substituted by a glycine residue. Further study has indicated that eight other family members are heterozygous for the variant; they are clinically normal with no evidence of splenomegaly or history of jaundice, although four of them showed a mild reticulocytosis.
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PMID:Hemoglobin Randwick or beta 15 (A12)Trp----Gly: a new unstable beta-chain hemoglobin variant. 338 7

Human alpha-crystallins were separated from fetal, young, senile nondiabetic and diabetic lenses. The effects of aging and diabetes mellitus were studied by fluorescence measurements, including emission maximum, quantum yield and polarization, using both intrinsic probes (tryptophan and non-tryptophan) and extrinsic probes [4-(N-iodoacetoxy)N-methylamino-7-nitrobenz-2-oxa-1,3-diazole (IANBD) and 6-(p-toluidinyl)naphthalene-2-sulfonate (TNS)]. Results indicate that diabetic effects (glycation and aggregation) give fluorescence change to a far greater extent than that of aging. This was demonstrated by a large decrease in tryptophan quantum yield and an increase in non-tryptophan quantum yield, and also by a decrease in polarization of non-tryptophan. The sulfhydryl (SH)-specific probe IANBD shows a blue-shift in emission maximum, a decrease in intensity and an increase in polarization. The hydrophobic probe TNS shows a decrease in both intensity and polarization. These results suggest that tryptophan oxidation, mixed disulfide formation and glycation, as well as other undetected post-translational modifications have partially unfolded the proteins, making the protein structure less rigid. The possible effect of this unfolding process is that proteins become more susceptible to aggregation.
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PMID:Fluorescence study of the effects of aging and diabetes mellitus on human lens alpha-crystallin. 356 49

The canine gastric mucosa has previously been shown to contain considerable amounts of a polypeptide with the immunologic and physicochemical characteristics and biologic activity of glucagon (IRG3500). Using mucosal pieces that remained viable for at least 8 h, we have demonstrated that IRG3500 is synthesized in this extrapancreatic tissue. Gel filtration and electrophoresis of extracts of mucosal pieces incubated with 3H-tryptophan, 3H-leucine, or 35S-methionine revealed small amounts of labeled, newly synthesized gastric IRG3500. No labeling of gastric IRG3500 was observed when the mucosa was incubated with 3H-proline, an amino acid not found in glucagon, in the presence of cycloheximide, or in isolated rat hepatocytes. Small amounts of newly synthesized IRG3500 were specifically immunoprecipitated by C-terminally directed glucagon antiserum gamma globulins. The rate of gastric IRG3500 biosynthesis in vitro was apparently unchanged in mucosal pieces from pancreatectomized dogs and unaffected by increased glucose or glucose lack during incubations. Thus we have provided evidence that a hormone of the endocrine pancreas can be synthesized in extrapancreatic tissues.
Diabetes 1985 Jan
PMID:Biosynthesis of glucagon (IRG3500) in canine gastric mucosa. 388 May 48

The metabolism of L-tryptophan by isolated liver cells prepared from control, adrenalectomized, glucocorticoid-treated, acute-diabetic, chronic-diabetic and insulin-treated chronic-diabetic rats was studied. Liver cells from adrenalectomized rats metabolized tryptophan at rates comparable with the minimum diurnal rates of controls, but different from rates determined for cells from control rats 4h later. Administration of dexamethasone phosphate increased the activity of tryptophan 2,3-dioxygenase (EC 1.13.11.11) 7-8-fold, and the flux through the kynurenine pathway 3-4-fold, in cells from both control and adrenalectomized rats. Increases in flux through kynureninase (EC 3.7.1.3) and to acetyl-CoA can be explained in terms of increased substrate supply from tryptophan 2,3-dioxygenase. The metabolism of tryptophan was increased 3-fold in liver cells isolated from acutely (3 days) diabetic rats, with a 7-8-fold increase in the maximal activity of tryptophan 2,3-dioxygenase. The oxidation of tryptophan to CO2 and metabolites of the glutarate pathway increased 4-5-fold, consistent with an increase in picolinate carboxylase (EC 4.1.1.45) activity. Liver cells isolated from chronic (10 days) diabetic rats metabolized tryptophan at rates comparable with those of cells from acutely diabetic rats, but with a 50% decrease in the activity of tryptophan 2,3-dioxygenase. The proportion of flux from tryptophan 2,3-dioxygenase to acetyl-CoA, however, was increased by 50%; this was indicative of further increases in the activity of picolinate carboxylase. Administration of insulin partially reversed the effects of chronic diabetes on the activity of tryptophan 2,3-dioxygenase and flux through the kynurenine pathway, but had no effect on the increased activity of picolinate carboxylase. The role of tryptophan 2,3-dioxygenase in regulating the blood tryptophan concentration is discussed with reference to its sensitivity to the above conditions.
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PMID:The role of tryptophan 2,3-dioxygenase in the hormonal control of tryptophan metabolism in isolated rat liver cells. Effects of glucocorticoids and experimental diabetes. 389 9


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