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 overcome the difficulties encountered in quantifying the insulin receptor number by Scatchard analysis, a radioimmunoassay (RIA) for the human insulin receptor (hIR) has been developed that uses an antibody raised against a synthetic peptide (Gly-Lys-Lys-Asn-Gly-Arg-Ile-Leu-Thr-Leu-Pro-Arg-Ser-Asn-Pro-Ser) corresponding to the carboxyl terminal of the hIR. A second peptide (Tyr-Gly-Arg-Ile-Leu-Thr-Leu-Pro-Arg-Ser-Asn-Pro-Ser) was used as a standard and allowed preparation of monoiodinated derivative of theoretical specific activity for use as the radioactive ligand. The assay is specific, highly reproducible, and sensitive, with a detection limit of 10 fmol of receptor. One mole of purified receptor, measured by Scatchard analysis or amino acid analysis, is read as one mole of receptor in the RIA with peptide being the standard. The assay is effective with receptor from multiple sources and could determine the decrease in number of insulin receptors seen in IM-9 lymphocytes after treatment with insulin (downregulation).
Diabetes 1989 Aug
PMID:Peptide-based radioimmunoassay for insulin receptor. Detection of insulin-stimulated downregulation in IM-9 lymphocytes. 266 3

This study provides explanation for conflicting evidence in the literature relating to changes in mitochondrial function and metabolic parameters during chemically induced diabetes. Diabetes of 3 days' duration (early ketosis) did not alter heart, kidney, or liver mitochondrial respiratory rates with glutamate or succinate even though serum glucose and triglycerides were elevated. Diabetes of 5 weeks' duration did not alter kidney or liver mitochondrial function in the fed adult rat although weight gain was depressed. The amount of kidney mitochondrial protein isolated per gram of tissue was increased by 30% in the diabetic. This increase was reversed by insulin treatment as were the other biochemical modalities measured. Superimposition of a 24-hr fast resulted in enhanced gluconeogenesis as measured by an animal weight loss of 17% within 24 hr (liver weight loss, 21%) and an elevation of serum urea nitrogen by 180% compared to fasted control. Respiratory rates of diabetic kidney mitochondria with glutamate were unaffected in the fasted animal whereas diabetic liver mitochondrial respiratory rates during succinate oxidation were reduced by 43%. Respiratory control was unchanged in the fasted diabetic rat. All the observed changes were reversed by insulin. Variation in the serum and liver metabolic indices (urea nitrogen, creatinine, glycerol, free fatty acids, free amino acids, triglycerides, and glucose) and liver mitochondrial responses to 7 weeks of chemically induced diabetes was affected by the rat strain, Sprague-Dawley versus Sherman, and rat weight, 72 g versus 222 g. Liver mitochondrial respirations in fed Sherman rats were not depressed by diabetes. Both rat strains had elevated liver free fatty acids and glutamate dehydrogenase activity in the diabetic state. Serum leucine, isoleucine, and valine were more elevated and serum lysine and arginine were more depressed in the diabetic Sprague-Dawley rat than in the Sherman rat. Conjectures on these results are presented in the text.
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PMID:Metabolic and mitochondrial disturbances in streptozotocin-treated Sprague-Dawley and Sherman rats. 293 62

Sulphonylureas lower blood glucose but other metabolic effects have been little studied. In an assessment of carbohydrate and amino acid metabolism in 9 patients with non-insulin-dependent diabetes mellitus (NIDDM) before and after 3 months' therapy with gliclazide, glycaemic control was improved (mean +/- S.D. glycosylated haemoglobin 13.8 +/- 1.9% before therapy, 10.2 +/- 2.1% after therapy (p less than 0.01], but fasting amino acid levels were not altered. In contrast, postprandial levels of branched chain amino acids (BCAA) were significantly reduced: total BCAA (valine, leucine, and isoleucine) 120 mins following a standard test meal fell from 717 +/- 71 mumol/l before therapy to 600 +/- 90 mumol/l after 3 months' therapy (p less than 0.01). This finding implies an increased action of endogenous insulin on skeletal muscle to promote uptake of BCAA postprandially and, in accord with this, peripheral insulin levels were significantly increased following drug treatment (peak insulin level 55.6 +/- 20.2 mU/l before therapy, 91.3 +/- 17.9 mU/l after therapy (p less than 0.01]. Sulphonylurea drugs therefore do not simply have a hypoglycaemic action but also affect amino acid metabolism in NIDDM patients.
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PMID:Effect of sulphonylurea administration on insulin secretion and amino acid metabolism in non-insulin-dependent diabetic patients. 295 Oct 64

1. Previous work has shown that the diabetogenic action of streptozotocin is reduced in rats adapted to a high-protein, carbohydrate-free diet and that plasma valine, leucine and isoleucine concentrations are markedly elevated in rats adapted to the high-protein diet. 2. To test the possibility that these branched-chain amino acids play a role in the beneficial effects of the high-protein diet, rats fed the control balanced diet were injected intraperitoneally with mixtures of valine, leucine and isoleucine (0.25 or 0.50 g/kg body weight of each amino acid), or with each of these amino acids separately (0.50 g/kg), 15 min before streptozotocin administration (40 mg/kg, intravenously). Arginine (0.50 g/kg) was administered in one experiment. Control animals received equal volumes of saline. 3. Rats previously injected with the amino acid mixtures showed a partial but significant reduction of diabetes severity as indicated by lower plasma glucose levels, higher rates of body weight gain and greater amounts of epididymal and retroperitoneal fat. No protection was observed after the administration of either valine, isoleucine, leucine or arginine. 4. These data suggest that the elevated levels of plasma branched-chain amino acids may account at least in part for the initial protective effect of high-protein diets against streptozotocin beta-cytotoxicity when the cells are first exposed to the drug.
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PMID:Administration of branched-chain amino acids reduces the diabetogenic effect of streptozotocin in rats. 296 88

Diabetes mellitus is a defect not only in glucose metabolism, but also in the metabolism of lipids and amino acids. Gas chromatographic and gas chromatographic--mass spectrometric profile analyses have contributed much to the understanding of the metabolic changes connected with this defect. Ketones are isolated by a gas-phase extraction and adsorption technique and profiled after thermal desorption. Organic acids are isolated by solvent extraction or anion exchange, derivatized and separated either as total acid profiles or subprofiles after pre-fractionation of the acid derivatives. The main results are as follows. (a) Increased total 4-heptanone is inherently connected with diabetes mellitus. Its urinary levels are elevated in therapeutically well controlled patients. (b) A general ketogenesis pathway leads to higher molecular weight ketone bodies in addition to the conventional ketone bodies. (c) During diabetic ketoacidosis, in addition to the fatty acids the following acids are elevated in serum and in urine: dicarboxylic acids resulting from omega- and beta-oxidation of monocarboxylic acids; oxomonocarboxylic acids as metabolites of the amino acids valine, leucine and isoleucine and as products of ketogenesis; and hydroxymonocarboxylic acids, also originating from amino acids and from ketogenesis.
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PMID:Gas chromatographic profiling of ketone bodies and organic acids in diabetes. 309 87

Competition between glucose and free fatty acids as metabolic fuels is supported by both in vitro and in vivo data, but whether amino acids can also compete with glucose as a source of energy in vivo remains to be established. To determine the effect of increased availability of an amino acid on whole-body glucose flux and glucose carbon uptake by the human forearm, five groups of overnight-fasted normal subjects were infused with either saline, leucine (at 0.5 or 1.0 mumol X kg-1 X min-1), isoleucine (0.5 mumol X kg-1 X min-1), or threonine (0.5 mumol X kg-1 X min-1). Plasma glucose concentrations and glucose flux decreased similarly in all groups. No significant changes in forearm output of leucine carbon, isoleucine carbon, or threonine were seen during saline infusion. In contrast, during leucine infusion there was a dose-dependent increase (r = .86, P less than .001) in leucine carbon uptake with increased arterial leucine and alpha-ketoisocaproate concentrations. During infusions of isoleucine and threonine, increases (P less than .05) in isoleucine carbon uptake and threonine uptake, respectively, were observed. Glucose uptake by forearm tissues did not change during the saline infusion, but it decreased (P less than .05) in all four groups receiving an amino acid infusion. Changes in leucine carbon uptake were strongly correlated (r = -.76, P less than .001) with changes in glucose uptake. Therefore, amino acids affect glucose uptake in human forearm tissue and presumably compete as oxidative fuels.
Diabetes 1987 Feb
PMID:Decreased uptake of glucose by human forearm during infusion of leucine, isoleucine, or threonine. 310 Mar 68

Previous studies showed that the diabetogenic action of streptozotocin is reduced in rats adapted to a high-protein, carbohydrate-free diet, that have markedly elevated plasma concentrations of valine, leucine and isoleucine. In order to test the role of these branched chain amino acids (BCAA) in the beneficial effects of the high-protein diets, rats adapted (15 days) either to a balanced synthetic diet, or to the same diet supplemented with BCAA were injected with streptozotocin (STZ) (40 mg/kg body weight) and maintained on the same diets after drug injection. Rats previously fed the BCAA enriched diet showed a partial but significant reduction in the severity of diabetes, as indicated by higher rates of body weight gain, lower food and water intake, lower excretion of glucose and higher serum insulin levels. Rats previously fed the control diet for 14 days, but transferred to the BCAA diet 3 days after STZ injection, also showed reduced severity of diabetes, as indicated by rates of body weight gain, water and food ingestion, glucose and insulin levels. The data suggest that the increased supply of BCAA is responsible, at least in part, for the previously reported beneficial effects of high-protein diets in rats with STZ-induced diabetes.
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PMID:Dietetic supplementation with branched chain amino acids attenuates the severity of streptozotocin-induced diabetes in rats. 322 89

Plasma amino acid concentrations were measured in six insulin-dependent diabetic women and seven non-diabetic women in early pregnancy while fasting and one hour after a standard meal. Fasting plasma levels of total amino acids and individual amino acids were similar in the two groups, excepting isoleucine, which was raised in the diabetics. One hour post-prandially total amino acid concentrations were similar in the two groups; however, mean concentrations of total branched chain amino acids and mean concentration of the individual amino acids, serine, valine, isoleucine, leucine and tyrosine were elevated in the diabetics. Amino acids are important in early islet development and in insulin secretion from fetal pancreas in vitro. The elevated post-prandial amino acid levels found in pregnant diabetics in early pregnancy may contribute to fetal islet hypertrophy and hyperinsulinaemia.
Diabetes Res Clin Pract 1986 Jun
PMID:Amino acid profiles in early diabetic and non-diabetic pregnancy. 374 58

Insulin-dependent diabetes mellitus (IDDM) induces plasma amino acid (AA) abnormalities, including low alanine and high branched-chain (BCAA). While insulin treatment restores plasma AA pattern, proline, methionine, valine, isoleucine, and total BCAA remain elevated in skeletal muscle intracellular water. This suggests that the restoration of plasma AA concentrations is not a satisfactory index of recovered AA metabolism in IDDM.
Diabetes 1985 Aug
PMID:Plasma and skeletal muscle free amino acids in type I, insulin-treated diabetic subjects. 389 23

The effect of diabetes (streptozotocin, 65 mg/kg ip), dietary protein intake (15-60%), and plasma amino acid concentrations on brain large neutral amino acid levels in rats was examined. After 20 days, the plasma concentrations of methionine and the branched chain amino acids (BCAA), valine, isoleucine, and leucine were increased in diabetic rats. In brain tissue, methionine and valine levels were increased but threonine, tyrosine, and tryptophan concentrations were depressed. Increased protein consumption promoted a diabetic-like plasma amino acid pattern in normal rats while enhancing that of diabetic animals. However, with the exception of threonine, glycine, valine, and tyrosine, there was little effect on brain amino acid levels. A good association was found between the calculated brain influx rate and the actual brain concentration of threonine, methionine, tyrosine, and tryptophan in diabetic animals. There was no correlation, however, between brain influx rate and brain BCAA levels. Thus, the brain amino acid pattern in diabetes represents the combined effects of insulin insufficiency and composition of the diet ingested on plasma amino acid levels as well as metabolic adaptation within the brain itself.
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PMID:The effect of insulin deficiency, dietary protein intake, and plasma amino acid concentrations on brain amino acid levels in rats. 404 90


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