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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Renal substrate exchange was examined in five male patients with insulin-dependent diabetes mellitus of several years' duration. Insulin was withheld for twenty-four hours prior to the study. A renal vein was catheterized from the femoral vein, and PHA-clearance was employed for the determination of effective renal blood flow. None of the patients was in ketoacidosis, but all were moderately hyperglycemic in the fasting states (16.8 +/- 1.5 mmol/L.) (225-384 mg./100 ml.). Nevertheless, no net release of glucose from the kidney was detectable. Instead, there was a significant net renal uptake of glucose (320 +/- 80 mumol/min.). In addition, there was a significant net uptake of glycerol and a net release of pyruvate. Renal amino acid exchange was similar to that reported for healthy subjects: glutamine, glycine, proline, and citrulline were taken up and serine, alanine, cystine, tyrosine, and threonine were released by the kidney. It is concluded that (a) in nonketoacidotic diabetics there is no net production of glucose by the kidney; (b) renal amino acid exchange in diabetics is similar to that of healthy individuals; and (c) the kidney is not an important gluconeogenic organ in human diabetes.
Diabetes 1975 Aug
PMID:Renal substrate exchange in human diabetes mellitus. 115 36

Insulin resistance in skeletal muscle may be an expression of the genetic basis of a common form of non-insulin-dependent diabetes mellitus (NIDDM) in humans. Impaired insulin action results from an apparent postreceptor defect in insulin signal transduction that limits the influence of the hormone on various protein serine/threonine kinases and phosphatases that are thought to contribute to the mechanism by which insulin affects intracellular events. The fact that numerous responses to insulin are affected suggests that the cause of insulin resistance involves an early step in insulin action. Therefore, we examined the influence of insulin on protein tyrosine phosphatase (PTPase) activities, which may counteract the protein tyrosine kinase activity of the insulin receptor in skeletal muscle of insulin-sensitive and insulin-resistant humans. Insulin infusion in vivo produced a rapid 25% suppression of soluble-PTPase activity in muscle of insulin-sensitive subjects, but this response was severely impaired in subjects who were insulin resistant. Insulin did not affect PTPase activity in the particulate fraction of muscle from either group, but basal particulate activity was 33% higher in resistant subjects than in sensitive subjects. Either or both of these abnormal characteristics of PTPase activities could be central to the causes of insulin resistance and NIDDM.
Diabetes 1991 Jul
PMID:Abnormal regulation of protein tyrosine phosphatase activities in skeletal muscle of insulin-resistant humans. 164 97

The insulin resistance seen in diabetes mellitus has been attributed partly to impaired autophosphorylation of the insulin receptor. It has been suggested that the phosphorylation of serine and/or threonine residues of the insulin receptor may reduce tyrosine autophosphorylation in streptozotocin-induced diabetic rats (STZ-D rats). To elucidate the mechanisms of decreased autophosphorylation of the insulin receptor in diabetic rats, we have investigated the effect of dephosphorylation of the insulin receptor by alkaline phosphatase on the insulin- and protein kinase-stimulating incorporation of 32P into the receptor of the liver from STZ-D rats. Both basal and insulin-stimulated autophosphorylations of the insulin receptor from STZ-D rats were significantly impaired to those from normal rats. Dephosphorylation of the insulin receptor by alkaline phosphatase resulted in an increase in insulin-stimulated autophosphorylation of the insulin receptor from STZ-D rats (43 +/- 13% to 66 +/- 14%, P less than 0.05), but not from normal rats (100% to 109 +/- 12%, NS). Although maximal autophosphorylation of the dephosphorylated insulin receptor was still lower in STZ-D rats than in normal rats, the increase in insulin-stimulated autophosphorylation of the insulin receptor from STZ-D rats by dephosphorylation was higher than that from normal (159.2 +/- 27.2% vs 108.0 +/- 12.4%, p less than 0.01), supporting the idea that the residues of the insulin receptor of STZ-D rats was highly phosphorylated.(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes Res 1991 May
PMID:Dephosphorylation of the insulin receptor partially restores the decreased autophosphorylation in streptozotocin induced diabetic rats. 181 77

Plasma and urinary concentrations of different amino acids were investigated during diabetic ketoacidosis (DKA) and 12, 24, 72 hours after initiation of therapy. In DKA, plasma concentration of glutamic acid, aspartic acid, valine, leucine and isoleucine significantly increased while that of asparagine and glutamine decreased compared to levels in well-controlled diabetic patients. The urinary excretion of branched-chain amino acids, histidine, serine and threonine was elevated while those of glutamic acid, glutamine, glycine and taurine were reduced. Among the different amino acids, histidine excretion had the highest variability. A strong correlation was found between the urinary excretion of several amino acids and that of the beta-2-microglobulin characterizing tubular dysfunction. Changes in the excretion of different amino acids reflect the altered metabolic state and renal function due to DKA.
Diabetes Res Clin Pract 1991 May
PMID:Changes in plasma and urinary amino acid levels during diabetic ketoacidosis in children. 190 67

This review discusses recent advances in understanding of the structure and function of the insulin receptor and insulin action, and how these relate to the clinical aspects of insulin resistance associated with non-insulin-dependent diabetes and other disorders. Improved understanding of the molecular basis of insulin resistance could ultimately lead to a better understanding of the causation of these conditions and the design of rational therapy to ameliorate them. Here, particular attention is devoted to the initial events that follow the binding of insulin to its receptor, including changes in insulin receptor phosphorylation. Receptor-mediated insulin resistance may be a consequence of various factors including increased serine/threonine phosphorylation of the receptor with decreased tyrosine phosphorylation, receptor desensitization, auto-antibodies to the receptor and inherited structural defects in the insulin receptor. Defects in insulin action could also arise at post-receptor events particularly glucose transport. Other circulating hormones, such as the newly characterised islet amyloid polypeptide (amylin), may also cause insulin resistance.
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PMID:Molecular mechanisms of insulin resistance. 202 55

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

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 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


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