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)

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

A photosensitive derivative of radiolabeled insulin, SANAH-125I-insulin, was prepared by reacting N-succinimidyl-6-(4'-azido-2'-nitrophenylamino) hexanoate (SANAH) with 125I-insulin. Cultured IM-9 cells were incubated with SANAH-125I-insulin at 16 degrees C in the dark. They were then washed, photolyzed, solubilized, and analyzed by SDS-polyacrylamide gel electrophoresis and autoradiography. Under disulfide reducing conditions, a single specific band of Mr 125,000 was obtained. The characteristics of the labeling of this band with SANAH-125I-insulin (specificity, time course, concentration effect) were the same as that of 125I-insulin interaction with the IM-9 cells and the labeling process did not affect cell viability. The solubilized photolabeled insulin receptor fraction was enriched by first adsorbing to agarose-bound wheat germ agglutinin and the material eluted with N-acetyl-D-glucosamine was then analyzed by SDS-PAGE and autoradiography. Under nonreducing conditions, a major receptor band of Mr 320 K and a minor band of 280 K were obtained. Upon disulfide bond reduction with increasing concentrations of dithiothreitol, a major band of Mr 125 K and two minor bands of Mr 210 K and 94 K were seen. When cells photolabeled at 16 degrees C were further incubated at 37 degrees C, there was a time-dependent loss of intact receptors into the incubation buffer. In contrast, no similar shedding of labeled receptors was observed from isolated rat adipocytes. Following shedding, the labeled IM-9 insulin receptors rapidly disappeared from the incubation buffer (half-time approximately 1.5 h). These results demonstrate the feasibility of photoaffinity labeling, characterizing, and following the fate of insulin receptor in viable cells. Thus receptor photoaffinity labeling should provide a suitable approach for studies of the biologic fate of insulin receptors in cells that are targets for insulin action.
Diabetes 1982 May
PMID:Photoaffinity labeling of insulin receptors in viable cultured human lymphocytes. Demonstration of receptor shedding and degradation. 715 33

The effect of chronic streptozotocin-induced diabetes was studied on intestinal microvillous membrane surface carbohydrate groups. After 7 weeks of diabetes, purified microvillous membranes were prepared from rat small intestine and surface galactoproteins identified by labeling with galactose oxidase/sodium boro[3H]hydride. Membrane surface sialic acid residues were labeled using the sodium metaperiodate/sodium boro[3H]hydride technique. Membranes were solubilized in SDS and protein labeling analyzed by acrylamide electrophoresis. Membranes from diabetic rats showed an 81% increase in galactoprotein labeling (P less than 0.02) while labeling of sialic acid residues was unchanged. The greatest increase in galactoprotein labeling occurred in protein monomers of Mr 116,000-200,000, where there was a 155% increase in labeling (P less than 0.005). These results indicate that intestinal microvillous membrane protein glycosylation is altered in chronic diabetes. This increase in surface membrane carbohydrates could explain the decreased rates of proteolytic degradation previously described for at least one microvillous protein. An increase in membrane galactose groups has also been noted in hepatocyte and kidney glomerular basement membranes, which suggests the presence of a systematic change in membrane protein glycosylation occurring as a result of the diabetic state.
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PMID:Alterations in labeling of cell-surface glycoproteins from normal and diabetic rat intestinal microvillous membranes. 731 89

21 patients (10 male, 11 female) aged between 11 months and 29 years with Shwachman's syndrome are reviewed. All patients had exocrine pancreatic insufficiency. Haematological features included neutropenia in 19 (95%), anaemia in 10 (50%), and thrombocytopenia in 14 (70%); one patient developed erythroleukaemia. Severe infections occurred in 17 (85%) from which 3 (15%) died. Only one child exceeded the 3rd centile for height, and growth retardation was particularly evident in the older patients. All had skeletal abnormalities or delayed skeletal maturation, or both. Metaphyseal dyschondroplasia affected 13 of the older patients and was associated with skeletal deformities. Eight of 9 children under 2 1/2 years had rib abnormalities. Respiratory function tests in children under 2 years demonstrated reduced thoracic gas volume and chest wall compliance. Older patients had reduced forced expiratory volume and forced vital capacity. Neurological assessment showed developmental retardation or reduced IQ assessments, or both, in 85% of patients studied. Other neurological abnormalities included hypotonia, deafness, and retinitis pigmentosa. Neonatal problems had been present in 16 (80%) of the patients and 5 were of low birthweights. Hepatomegaly with biochemical evidence of liver involvement occurred in the younger patients and resolved with age. Other associated features included dental abnormalities, renal dysfunction, an icthyotic maculopapular rash in 13 (65%), delayed puberty, diabetes mellitus, and various dysmorphic features. These findings stress the diverse manifestations of the syndrome and extend knowledge on a number of aspects. Sibship segregation ratios support an autosomal mode of inheritance and an hypothesis for the pathophysiological basis of this syndrome is advanced.
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PMID:Shwachman's syndrome. A review of 21 cases. 743 69

Inhibition of insulin secretion by galanin is pertussis toxin (PTX) sensitive, suggesting the activation of one or more heterotrimeric (alpha, beta, gamma) G-proteins (Gi/Go). Multiple effectors, including the K+ATP and L-type Ca2+ channels, adenylyl cyclase, and an as yet unidentified system at a site close to exocytosis, are modulated by galanin. Therefore, it is necessary to delineate the particular G-proteins activated by the galanin receptor as a first step to understanding its net cellular response. During specific conditions, cholera toxin (CTX) can ADP-ribosylate the alpha i/alpha o-subunits of the PTX-sensitive substrates but only during receptor/G-protein interaction. Therefore, we used CTX-catalyzed ADP ribosylation to identify galanin receptor-associated G-protein alpha-subunits in RINm5F cells. Galanin enhanced the ADP ribosylation of membrane proteins separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) in two bands at 39,000 and 42,000 M(r). This labeling was blocked in membranes prepared from PTX-treated cells, enhanced by Mg2+, and showed a biphasic dependence on exogenous guanine nucleotides. Identification of the CTX ADP-ribosylated G-proteins by immunoprecipitation with selective antisera indicate activation by the galanin receptor of alpha i1 and alpha i3, which have the same mobility on SDS-PAGE (42,000 M(r)), and alpha i2 (39,000 M(r)). These studies provide evidence for the activation of multiple G-proteins by receptors for galanin in RINm5F cells.
Diabetes 1994 Jan
PMID:ADP ribosylation by cholera toxin identifies three G-proteins that are activated by the galanin receptor. Studies with RINm5F cell membranes. 750 45

Previous studies support a role for insulin-like growth factor-binding protein-1 (IGFBP-1) in modulating insulin-like growth factor (IGF) availability for glucose homeostasis. We have developed a radioimmunoassay (RIA) for rat IGFBP-1 (rIGFBP-1) and have examined the regulation of circulating levels by nutritional and hormonal status. Rabbit antisera were raised against pure rIGFBP-1, and an assay was established with a sensitivity of 50 pg. In the rat, serum IGFBP-1 concentrations decrease with increasing developmental age. They were highest in fetal rat serum, exceeding 4 mg/L, and decreased to < 0.1 mg/L in adult animals. Serum rIGFBP-1 levels increased during fasting, 6-fold after 24 h and 18-fold after 48 h, and were suppressed to levels identical to ad libitum-fed control rats within 2 h of refeeding. Fasting levels were > 2-fold higher in female than male animals. IGFBP-1 concentrations were suppressed by > 50% in two rat models of insulin resistance. Levels increased in STZ-induced (streptozotocin) diabetes and were suppressed to normal with insulin treatment. Exercise stimulated rIGFBP-1 concentrations in fasting animals. On immunoblotting after SDS-PAGE (sodium dodecyl sulfate-polyacrylamide gel electrophoresis), rIGFBP-1 in serum appeared as a doublet with molecular masses at 31 and 33 kD. The components of this doublet did not vary across the range of experimental conditions. These observations indicate that the pattern of regulation of rIGFBP-1 is similar to that seen in previous studies of human IGFBP-1, with age, sex, and nutritional status being important regulators.(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes 1994 Feb
PMID:Regulation of insulin-like growth factor-binding protein-1 in rat serum. 750 68

Microalbuminuria is considered to be an early indicator of diabetic nephropathy. In this report, we developed an enzyme-linked immunosorbent assay (ELISA) for the measurement of urinary albumin (UA) and examined UA in 38 patients with insulin-dependent diabetes mellitus (IDDM). The assay range of ELISA for albumin was 5-1,000 ng/ml, and the albumin levels determined by ELISA were well correlated with those by immunoagglutination methods. The UA values of daytime single-void specimens in control subjects, which correlated significantly with UA excretion rates (micrograms/minute) in 24-hour urine, were 10.9 +/- 8.2 micrograms/mg creatinine. In 38 IDDM patients, there were four cases with microalbuminuria and one case with overt nephropathy. Their disease duration was longer than 8 years, and the diabetic control was fair to poor. On SDS-PAGE analysis. the urinary protein of the cases with microalbuminuria consisted mainly of albumin, and in the case of nephropathy, an IgG band was also detected. The measurements of UA in single-void specimens by ELISA is a satisfactory approach to detect impending nephropathy in IDDM patients.
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PMID:An enzyme-linked immunosorbent assay for urinary albumin in patients with insulin-dependent diabetes mellitus. 768 36

Methylglyoxal is an endogenous metabolite that increases in diabetes and has been implicated in some of its long-term complications such as retinopathy, neuropathy and cataract. We investigated the reaction of methylglyoxal with isolated human and bovine lens crystallins (alpha, beta H, beta L and gamma). After 7 days incubation at 37 degrees C and pH 6.9, the reaction of methylglyoxal with lens proteins yielded stable adducts that exhibited fluorescent properties. SDS-polyacrylamide gel electrophoresis was used to monitor aggregation and crosslinking of the modified protein and autoradiography showed that [14C]methylglyoxal was incorporated into all the protein bands. Bovine gamma-crystallin was the most reactive towards methylglyoxal. Reaction of methylglyoxal with bovine gamma II-crystallin, which is found mainly in the lens nucleus, could alter the change surface network of the molecule, resulting in aggregation, increased light scattering and hence cataract. Modification of gamma II-crystallin by methylglyoxal produced an overall loss of positive charge and an increase in molecular weight and non-disulfide covalent crosslinking. Amino acid analysis of the modified gamma II-crystallin showed a loss of 47% of arginine residues.
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PMID:The reaction of methylglyoxal with human and bovine lens proteins. 782 33


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