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)

The binding profiles of insulin autoantibodies (IAA) and insulin antibodies (IA) to highly purified species variants and fragments of insulin were studied in direct immunospecific enzyme-linked immunosorbent assay (ELISA) and indirect absorption experiments with insulins covalently coupled to Sepharose beads. Five of 10 IAA-containing sera from insulin-naive nondiabetics that bound whole human (H) insulin did not bind whole porcine (P) or whole bovine (B) insulins. These sera bound H insulin B-chain but not P B-chain or desalanated P insulin, suggesting they were dependent on the presence of threonine B30. The other 5 IAA-containing sera bound H, P, B, and desalanated porcine insulins, but only 1 bound isolated B-chains. All 10 IA-containing sera from insulin-treated diabetics bound H, P, B, and desalanated P insulins, but only 1 bound to human (and porcine) B-chain. Further binding studies with ovine, rabbit, rat, and guinea pig insulins confirmed the H (threonine B30) specificity of the 5 IAA-containing sera. B30 residues do not appear to be dominant, however, when insulin is administered exogenously. Instead, IA bind predominantly to A-chain or conformational determinants involving both chains. Scatchard analysis of a representative H insulin-specific IAA serum suggested that it contained a single binding affinity, whereas analysis of a representative IA-diabetic serum suggested it contained several different affinities.
Diabetes 1987 Jan
PMID:Differences in epitope restriction of autoantibodies to native human insulin (IAA) and antibodies to heterologous insulin (IA). 243 39

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

Metabolic profiling of urinary organic acids from patients with juvenile-onset (Type 1) diabetes mellitus have revealed significantly elevated levels of 2-hydroxybutyric and 4-deoxythreonic acids. To test the hypothesis that these metabolites, as well as 4-deoxyerythronic acid, are derived from L-threonine, stable isotope-labeled threonine was infused into an insulin-deficient dog and the incorporation of 13C into these metabolites was monitored by gas chromatography/mass spectrometry. Electron ionization was relatively insensitive, but positive chemical ionization with ammonia as the reactant gas gave both protonated molecules and [M + NH4]+ ions, which could be analysed by selected ion monitoring. The isotope-labeled species of 2-hydroxybutyric, 4-deoxyerythronic and 4-deoxythreonic acids were observed, but 13C was not incorporated into other organic acids. Thus, it is proposed that L-threonine is a precursor of these metabolites.
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PMID:Urinary metabolites of L-threonine in type 1 diabetes determined by combined gas chromatography/chemical ionization mass spectrometry. 294 47

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

The purpose of this investigation was to collect data concerning changes in carbohydrate and amino acid metabolism following different surgical operations (thoracotomies, laparotomies). Blood of 20 metabolically healthy adult surgical patients, who had to undergo elective surgery (lobectomies, pneumonectomies, colon resections) was examined preoperatively, immediately postoperatively and from 1.-4.postoperative day. The experimental data during the perioperative phase showed a similar pattern in both groups of patients: We found a significant elevation in the blood glucose level and there was also a rise in plasma cortisol and plasma free fatty acids levels. We found no significant changes of blood lactate, plasma insulin and branched chain amino acids. Simultaneously we found a drop in plasma albumin, pre-albumin and some glucoplastic amino acids (ALA, GLN, THR, PRO). It is concluded that major abdominal and thoracic surgery give rise to a nonspecific stress situation reflected in carbohydrate and amino acid metabolism with the following metabolic symptoms: Raised lipolysis and gluconeogenesis, disturbance of glucose utilisation and obvious peripheral insulin resistance. These perioperative metabolic effects show some similarities to the metabolic situation in diabetes mellitus type 2.
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PMID:[Postaggression metabolism following laparotomy and thoracotomy]. 328 Feb 68

Distribution and cytotoxic function of lymphocyte subpopulations were studied in 20 patients with type I, in 20 patients with type II diabetes mellitus and in 40 control subjects. The percentage, the absolute number of (EA), (E Thr), (TM) subsets and the rate of (E Thr) (E Ths) and (TM/) (TG) cells were found to be higher in type I and lower in type II diabetic patients than in controls. This opposite tendency in the distribution of T-lymphocyte subsets may be related to the duration of diabetes. Simultaneously a significant cytotoxic capacity of U, null, T, (TG)-lymphocytes was observed against human pancreas extract-coated targets in almost all 18 out of 20 of type I, but only in a few cases (5 out of 20) of type II diabetic patients. These five patients needed insulin therapy six months later. The T and (TG)-lymphocytes had the largest killer activity in both diabetic groups. Lymphocyte-mediated cytotoxicity seems to be a specific method which is suitable for the study of in vitro sensitization against pancreas tissue, and it might predict insulin dependency in type II diabetic patients.
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PMID:T-lymphocyte subsets and their cytotoxic capacity in patients with type I and type II diabetes mellitus. 349 31

The two human insulins of clinical importance are (a) semisynthetic human insulin prepared from pork pancreas by enzymatically substituting threonine for alanine-the last amino acid in the beta chain-thereby transforming pork insulin in vitro to human insulin; and (b) biosynthetic human insulin synthesized biotechnologically in Escherichia coli-K12. Using this latter technique, it is possible to produce mass quantities of highly purified insulin for the treatment of insulin-dependent diabetics, avoiding the problems inherent in supplies of insulin produced from animal pancreas. It has been suggested that to avoid confusion the two human insulins should be called semisynthetic human insulin of pork origin and biosynthetic human insulin of E. coli origin, respectively. These insulins have four advantages over highly purified animal insulins: (a) they induce lower titers of circulating insulin antibodies; (b) their subcutaneous injection is associated with fewer skin reactions; (c) they are absorbed more rapidly from the injection site; and (d) less degradation occurs at the site of injection. These data indicate that newly diagnosed insulin-dependent diabetes, particularly in children, should be treated with either of the two human insulins. The warranty against inadequate supplies of insulin offered by biosynthetic human insulin makes the use of pork insulins unnecessary and beef insulins totally useless.
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PMID:Human insulin. 388 92

The transient diabetes, observed in ducks after subtotal pancreatectomy, induces hyperglycaemia and hyperamino-acidaemia. Threonine and alanine are quantitatively the most important amino acids in both normal and diabetic animals, suggesting a particular role of threonine in amino acid metabolic pathways in the duck. The hyperaminogenic role of the decreased insulin levels, and the neoglucogenic effect of a low, but not negligible, glucagon secretion, during diabetes, are discussed.
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PMID:Amino acids in normal and diabetic ducks. 389 68

High-affinity monoclonal antibodies (MAB) were obtained from lymph node cell fusions. Affinities ranging from 0.8 X 10(9) L/M to 5.2 X 10(9) L/M were calculated from binding studies with monoiodinated human, bovine, and porcine insulins and human proinsulin. Two monoclonal antibodies were specific for human insulin, recognizing an epitope involving the amino acid B-30 (Thr). Another two monoclonal antibodies were bound to the C-terminal end of the B-chain near B-30. The B-chain-specific monoclonal antibodies did not bind human proinsulin. One monoclonal antibody recognized the A-chain loop in the positions A-8 to A-10. This antibody bound also to human proinsulin. It was concluded that the A-chain loop is exposed on the surface of proinsulin, while the C-terminal B-chain is not available for binding. The study shows that monoclonal antibodies can be used to characterize structures of insulin and proinsulin. In contrast to x-ray studies, the molecules can be used at low concentrations in soluble form. It is suggested to use monoclonal antibodies for the screening of atypical insulins in the serum of diabetic patients and for the further refinement of insulin and proinsulin measurements.
Diabetes 1985 Aug
PMID:Recognition of human insulin and proinsulin by monoclonal antibodies. 389 22

Mammalian glucagon is thought to be highly conserved. Glucagons from pig, cow, human, rat, and hamster have identical amino acid sequences, whereas the amino acid contents of rabbit and camel glucagons are consistent with this 29-amino acid sequence. It had earlier been reported that guinea pig (GP) glucagon contains 40 amino acids. In the current study, glucagon was purified from two GP pancreata by a series of three HPLC steps after acid-alcohol extraction and acetone precipitation. GP glucagon is a 29-amino acid peptide that differs from other mammalian glucagons by substitution of Gln for Asp in position 21, Leu for Val in position 23, Lys for Gln in position 24, Leu for Met in position 27, and Val for Thr in position 29. In view of the marked changes in the COOH-terminal of GP glucagon, receptor binding studies were performed using both rat and GP liver membranes. Labeled synthetic porcine glucagon has similar binding in the two systems and its binding is inhibited to a similar degree by synthetic porcine glucagon, whereas GP glucagon is 10-fold less potent at inhibiting binding in both systems. This suggests that glucagon receptor binding sites in the GP are evolutionarily more conserved than is GP glucagon.
Diabetes 1986 May
PMID:Guinea pig glucagon differs from other mammalian glucagons. 395 84


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