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)

Insulin receptors on viable rat adipocytes were affinity-labeled using a biologically active and photosensitive analogue of insulin, 125I-B2(2-nitro, 4 azidophenylacetyl)-des-PheB1-insulin (125I-NAPA-DP-insulin). The radiolabeled proteins were identified by SDS polyacrylamide gel electrophoresis and autoradiography. Binding of 125I-NAPA-DP-insulin (40 ng/ml) to rat adipocytes at 16 degrees C, followed by photolysis, resulted in the specific labeling of essentially one protein with an apparent molecular weight of 430-450,000 daltons. When this radiolabeled protein was treated with dithiothreitol prior to electrophoresis, specific labeling occurred predominantly in a 125,000-dalton protein and to a lesser extent in a 90,000-dalton protein. In addition, there was a minimal amount of specific labeling of a 115,000-dalton protein. Under certain experimental conditions, the nonreduced form of the photoaffinity-labeled receptor appeared as a heterogeneous population of proteins having apparent molecular weights of 430,000, 350,000, and 270,000 daltons. Subsequent to photoaffinity labeling of insulin receptors at 16 degrees C, adipocytes were incubated at 37 degrees C for various periods of time to allow for internalization. This resulted in an initial rapid loss of radioactivity in the 430,000- and 125,000-dalton bands. At 60 min the amount of radioactivity in each of these bands was approximately 50% of that present before incubation at 37 degrees C and stayed constant for 120 min. A first-order plot of the decline in receptor-associated radioactivity was biphasic with the initial phase having a half-life of 1.4 h.(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes 1983 Nov
PMID:Degradation of insulin receptors in rat adipocytes. 635

Insulin binding and processing was studied in monolayer cultures of bovine aortic endothelial cells. Specific 125I-insulin binding was both time and temperature dependent. Maximum binding at 37 degrees C occurred at 90 min, and was 3.8%/mg protein and, at 15 degrees C, 7%/mg protein at 4 h. 125I-insulin was crosslinked to its receptor using disuccinimidyl suberate (DSS), and the structure of the receptor complex was identified by SDS-polyacrylamide gel electrophoresis and autoradiography; a major band with Mr = 145,000 was identified, which corresponds to the alpha-subunit of the insulin receptor reported in other tissues. Receptor-bound insulin was internalized, and both the rate and the amount of internalization were temperature dependent. The rate of internalization was slowest at 4 degrees C, and fastest at 37 degrees C, and the maximum amount of 125I-insulin internalized in 120 min was 16% at 4 degrees C, 45% at 15 degrees C, and 81% at 37 degrees C. Despite the high rate of internalization, endothelial cells do not appear to degrade insulin significantly, as determined by gel chromatography and TCA solubility (7% at 4 h) of media-associated radioactivity. In addition, the majority of internalized insulin (75%) was released by 60 min, largely as intact insulin. Chloroquine treatment at high concentration did not exert any major effect on insulin binding or degradation within the first 60 min, but thereafter produced a marked increase in cell-associated radioactivity.(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes 1984 Aug
PMID:Processing of insulin by bovine endothelial cells in culture. Internalization without degradation. 637 2

The effects of insulin and insulin-like growth factor I (IFG-I) on protein synthesis were compared in muscle isolated from lean and goldthioglucose (GTG)-obese mice. Two types of skeletal muscles, the red soleus and the white extensor digitorum longus (EDL) muscles, were studied. In muscles from lean mice, 6.7 nM insulin and 50 nM IGF-I caused a similar maximal stimulation of tyrosine incorporation in total proteins (40% increase). However, the potency of IGF-I was only 5-10% that of insulin both in soleus and in EDL muscles (EC50 approximately equal to 6 nM for IGF-I and 0.5 nM for insulin). Basal rate of protein synthesis was identical in muscles from GTG-obese and lean mice. Similarly, a comparable increase in the rate of protein synthesis was obtained using maximally effective concentrations of insulin and IGF-I in both lean and GTG-obese animals. SDS-polyacrylamide gel electrophoresis analysis of proteins labeled with 35S-methionine confirmed that, in muscles from lean and GTG-obese animals, insulin and IGF-I increased overall protein synthesis in a similar manner. These results suggest that the protein synthesis machinery is not impaired in GTG-induced obesity, which is therefore not associated with resistance to insulin for its effect on protein metabolism.
Diabetes 1983 May
PMID:Insulin and insulin-like growth factor I. Effects on protein synthesis in isolated muscles from lean and goldthioglucose-obese mice. 640 79

Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of detergent solubilized cytochrome P-450 fractions from normal and diabetic female rat liver microsomes revealed the induction of a 52,000 molecular weight microsomal hemeprotein in diabetic liver. Two major P-450 hemeproteins (DB IIA and DB IIB) were subsequently isolated from solubilized diabetic female rat hepatic P-450 fractions, while normal rat liver yielded only one major microsomal P-450, N IIA. When examined in a reconstituted drug metabolizing system, the aniline hydroxylation rate catalyzed by DB IIB (52,000 molecular weight) was 157% and 78% greater than the rates catalyzed by N IIA and DB IIA, respectively. The rates of ethylmorphine metabolism catalyzed by N IIA and DB IIB were similar; however, the rate of ethylmorphine metabolism catalyzed by DB IIA (54,000 molecular weight) was approximately 42% greater than the rates catalyzed by either N IIA or DB IIB. These results are compared to those previously obtained with P-450s isolated from diabetic male rat liver and indicate that diabetes induces P-450s with specific catalytic activities which can account for both the sex-dependent and sex-independent alterations in drug metabolism observed in diabetic rat liver.
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PMID:Catalytic activities of cytochrome P-450 from female rat liver: correlation with sex differences in drug metabolism in diabetic liver. 641 61

In experimental diabetes, a number of intestinal brush-border hydrolases and transport systems are stimulated. In this study, we assessed possible effects of diabetes on the composition and membrane fluidity of rat intestinal brush-border membranes that might correlate with these functional changes. We found similar proportions of lipid and protein in the diabetic and control preparations, although there was a considerable increase in total membrane from the diabetic rats, presumably reflecting mucosal hyperplasia. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of membrane protein revealed an increase in the bands corresponding to sucrase-isomaltase, consistent with an increased enzyme activity of sucrase. Membrane lipid analysis revealed only a decrease in fatty acids of the neutral lipid fraction of diabetics--a change that may well have occurred during membrane preparation. 1-6-Diphenyl-1,3,5-hexatriene fluorescence polarization data, obtained as a function of temperature, was similar for the diabetic and control rats, with a three-phase linear model superior to one- and two-phase linear or quadratic models. The overall composition of the intestinal brush-border membrane, unlike other plasma membranes, appears little affected by experimental diabetes.
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PMID:Intestinal mucosa in diabetic rats: studies of microvillus membrane composition and microviscosity. 662 63

Sodium dodecyl sulfate-polyacrylamide gel electrophoresis was used to determine the effect of diabetes on the cytochrome P-450-region proteins of rat liver microsomes. Compared to normal microsomes, diabetic microsomes from both male and female rats exhibited distinct increases as well as decreases in the hemeproteins of this region. These results support the concept that the substrate specific changes in drug metabolism observed in diabetic rats may be related to specific alterations in the hepatic cytochrome P-450 hemeprotein population.
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PMID:Alterations in hepatic microsomal cytochrome P-450 hemeproteins in diabetic rats. 676 19

The amount of nonenzymatic glycosylation present in normal and diabetic rat peripheral nerve myelin, whole brain, brain myelin, and individual myelin protein components was determined using NaB3H4 reduction followed by either boronic acid affinity chromatography or SDS-polyacrylamide gel electrophoresis (SDS-PAGE). Diabetic peripheral nerve myelin (PNS-M) showed a 5.2-fold increase over normal, indicating that myelin is the major peripheral nerve component undergoing excessive glycosylation in diabetes. SDS-PAGE of diabetic and normal PNS-M showed no differences in the pattern of protein bands or in the distribution of glycosylated adducts. However, in the diabetic, the amount of incorporated radioactivity was 3.74 times greater in the P0 protein and 2.8 times greater in the high-molecular-weight material that did not enter the gel. In whole brain, a 2.4-fold increase in the amount of nonenzymatic glycosylation was observed when diabetic was compared with normal, while diabetic brain myelin (CNS-M) was 3.8 times more glycosylated than normal brain myelin. SDS-PAGE of diabetic and normal CNS-M, like that of PNS-M, showed no differences in the pattern of protein bands or in the distribution of glycosylated adducts. The amount of incorporated radioactivity, however, was 3.18 times greater in the proteolipid region, 2.37 times greater for basic myelin protein, and 2.9 times greater for the high-molecular-weight proteins that did not enter the gel. This excessive nonenzymatic glycosylation of the main peripheral and central nervous system myelin components may contribute to the functional abnormalities of myelinated neurons associated with diabetes.
Diabetes 1983 Jul
PMID:Excessive nonenzymatic glycosylation of peripheral and central nervous system myelin components in diabetic rats. 686 12

Polyadenylated RNA extracted from anglerfish islets was translated in a wheat germ cell-free system containing [35S]methionine in the presence and absence of microsomal membranes prepared from a canine pancreas. Labeled translation products were analyzed by immunoprecipitation with an antiserum to porcine glucagon, followed by electrophoresis of the translation products and immunoprecipitated proteins on SDS polyacrylamide gels. In the absence of microsomal membranes two proteins of Mr = 14,500 and Mr = 12,500 were specifically immunoprecipitated with antiglucagon serum. Addition of microsomal membranes to the translation reactions resulted in a diminution of the labeled protein of Mr = 14,500 and a marked increase in the immunoreactive protein of Mr = 12,500. The protein of Mr = 12,500 was resistant to degradation by proteolytic enzymes added to translation reactions, indicating that it was segregated within microsomal vesicles. These results are consistent with synthesis of anglerfish islet glucagon in the form of a pre-prohormonal precursor (Mr = 14,500) containing a leader sequence that is cotranslationally cleaved from the protein by enzymes associated with microsomal membranes to produce a smaller intermediate prohormonal precursor (Mr = 12,500) of pancreatic glucagon (Mr = 3500).
Diabetes 1980 Jul
PMID:Glucagon precursors identified by immunoprecipitation of products of cell-free translation of messenger RNA. 699 42

Detergent-solubilized hepatic microsomal fractions from alloxan diabetic rats exhibited a 52,000 molecular weight hemeprotein band that was not present in the sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) protein profiles of identically solubilized hepatic microsomal fractions from normal, 3-methylcholanthrene- or phenobarbital-treated rats. This 52,000 mol. wt hemeprotein band disappeared from the protein profile of insulin-treated diabetic rat liver to yield the SDS-PAGE profile of normal rat liver. When P-450 hemeproteins were purified by lauric acid affinity and hydroxylapatite chromatography from solubilized microsomes, only the diabetic rat had a 52,000 mol. wt P-450. This distinct 52,000 mol. wt diabetes-induced P-450 interacted with type II compounds to yield a 2-fold greater absorbance change than was observed with the purified P-450s from either the normal or the chemically induced rats. The properties of this unique 52,000 mol. wt P-450 suggest that it may be the catalytic component responsible for the increased rate of type II substrate (aniline) metabolism observed in the diabetic rat.
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PMID:Effect of diabetes on rat liver cytochrome P-450. Evidence for a unique diabetes-dependent rat liver cytochrome P-450. 715 Mar 59

We have grown the EHS (Engelbreth-Holm, Swarm) tumor in normal and genetically diabetic mice (db/db) and measured some components of basement membrane produced in the tumor. These studies showed similar amounts of total protein in control and diabetic tissue and similar patterns of proteins on SDS gel electrophoresis of extracts of the tissue. Laminin, a basement membrane specific glycoprotein utilized as an attachment factor by epithelial cells, was present in increased amounts in diabetic tissue. In contrast, the amount of BM-1 (heparan sulfate) proteoglycan was reduced. Less 35S-sulfate was incorporated into this proteoglycan, and the proteoglycan, but not its component glycosaminoglycans, was heterogeneous in size. The data indicate that either the synthesis of proteoglycan was decreased or its degradation was increased in diabetic tissue. Since the heparan sulfate proteoglycan serves to block the passage of anionic macromolecules through the basement membrane, decreased levels could account for the increased porosity of diabetic basement membrane. Compensatory synthesis of the basement membrane components to restore normal permeability could account for the thickened basement membranes observed in diabetes.
Diabetes 1982 Feb
PMID:Alterations in the basement membrane (heparan sulfate) proteoglycan in diabetic mice. 715 28


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