Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To investigate the possible mechanisms of the alterations in morphine-induced analgesia observed in diabetic mice, we examined the influence of streptozotocin-induced (STZ-induced) diabetes on analgesia mediated by the different opioid receptors. The antinociceptive potency of morphine (10 mg/kg), administered s.c., as determined by both the tail-pinch and the tail-flick test, was significantly reduced in diabetic mice as compared to that in controls. Mice with STZ-induced diabetes had significantly decreased sensitivity to intracerebroventricularly (i.c.v.) administered mu-opioid agonists, such as morphine (10 micrograms) and [D-Ala2,N-Me Phe4,Gly-ol5]enkephalin (DAMGO, 0.5 micrograms). However, i.c.v. administration of [D-Pen2,5]enkephalin (DPDPE, 5 micrograms), a delta-opioid agonist, and U-50,488H (50 micrograms), a kappa-opioid agonist, produced pronounced antinociception in both control and diabetic mice. Furthermore, there were no significant differences in antinociceptive potency between diabetic and control mice when morphine (1 microgram), DAMGO (10 micrograms), DPDPE (0.5 micrograms) or U-50,488H (50 micrograms) was administered intrathecally. In conclusion, mice with STZ-induced diabetes are selectively hyporesponsive to supraspinal mu-opioid receptor-mediated antinociception, but they are normally responsive to activation of delta- and kappa-opioid receptors.
 ...
PMID:Streptozotocin-induced diabetes selectively alters the potency of analgesia produced by mu-opioid agonists, but not by delta- and kappa-opioid agonists. 131 65

DNA polymorphisms in the glucokinase gene have recently been shown to be tightly linked to early-onset non-insulin-dependent diabetes mellitus in approximately 80% of French families with this form of diabetes. We previously identified a nonsense mutation in exon 7 in one of these families and showed that it was the likely cause of glucose intolerance in this dominantly inherited disorder. Here we report the isolation and partial sequence of the human glucokinase gene and the identification of two missense mutations in exon 7, Thr-228----Met and Gly-261----Arg, that cosegregate with early-onset non-insulin-dependent diabetes mellitus. To assess the molecular mechanism by which mutations at these two sites may affect glucokinase activity, the crystal structure of the related yeast hexokinase B was used as a simple model for human beta-cell glucokinase. Computer-assisted modeling suggests that mutation of Thr-228 affects affinity for ATP and mutation of Gly-261 may alter glucose binding. The identification of mutations in glucokinase, a protein that plays an important role in hepatic and beta-cell glucose metabolism, indicates that early-onset non-insulin-dependent diabetes mellitus may be primarily a disorder of carbohydrate metabolism.
 ...
PMID:Human glucokinase gene: isolation, characterization, and identification of two missense mutations linked to early-onset non-insulin-dependent (type 2) diabetes mellitus. 150 86

Denaturing gradient gel electrophoresis (DGGE) has been used to screen for mutations in the insulin receptor gene. Each of the 22 exons was amplified by the polymerase chain reaction (PCR). For each exon, one of the two PCR primers contained a guanine-cytosine (GC) clamp at its 5' end. The DNA was analyzed by electrophoresis through a polyacrylamide gel containing a gradient of denaturants. Two geometries for the gels were compared; the gradient of denaturants was oriented either parallel or perpendicular to the electric field. The sensitivity of the technique was evaluated by determining whether DGGE succeeded in detecting known mutations and polymorphisms in the insulin receptor gene. With parallel gels, 12 of 16 sequence variants were detected. The use of perpendicular gels increased the sensitivity of detection so that all 16 sequence variants were successfully detected when DNA was analyzed by a combination of perpendicular and parallel gels. Furthermore, DGGE was used to investigate a patient with leprechaunism whose insulin receptor genes had not previously been studied. Two mutant alleles were identified in this patient. The allele inherited from the father had a mutation substituting alanine for Val-28; in the allele inherited from the mother, arginine was substituted for Gly-366.
Diabetes 1992 Apr
PMID:Detection of mutations in insulin receptor gene by denaturing gradient gel electrophoresis. 160 67

The insulin-like growth factor-binding proteins IGFBP-1 and IGFBP-2 are low mol wt IGFBPs that are similar in structure. They are not glycosylated and have a homologous amino acid sequence, including the number and position of 18 cysteine residues and a carboxyl-terminal Arg-Gly-Asp sequence that can be recognized by cell adhesion receptors. The present study demonstrates that expression of mRNAs encoding the two BPs differs in some fetal rat tissues and in the livers of adult rats after hypophysectomy, fasting, or streptozotocin-induced diabetes. As determined by Northern blot hybridization using cDNA probes for rat IGFBP-2 or human IGFBP-1, both mRNAs are expressed at high levels in liver of 21-day gestation and 1-day-old rats and at lower levels in 21- and 65-day-old rat liver. Levels of both mRNAs are higher in liver than in other fetal rat tissues. The relative abundance of the two mRNAs in most fetal tissues is similar to that in liver, except that kidney and brain have 8-fold and more than 25-fold higher relative levels of IGFBP-2 mRNA, respectively. IGFBP-2 mRNA is about 10- to 20-fold increased after hypophysectomy or fasting, whereas IGFBP-1 mRNA is relatively unchanged. IGFBP-2 mRNA levels are decreased completely by refeeding fasted rats for 3 days, but only partially decreased by treatment of hypophysectomized rats with GH, cortisone acetate, T4, and testosterone for 4 days.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Different tissue distribution and hormonal regulation of messenger RNAs encoding rat insulin-like growth factor-binding proteins-1 and -2. 169 19

A radioimmunoassay for the GLUT1 glucose transporter was developed with a synthesized peptide based on the sequence of the cDNA for GLUT1. A peptide corresponding to the COOH-terminal domain of the GLUT1 glucose transporter (Thr-Pro-Glu-Glu-Leu-Phe-His-Pro-Leu-Gly-Ala-Asp-Ser-Gln-Val) was synthesized and conjugated to keyhole limpet hemocyanin through the NH2-terminal of the peptide. An antibody was raised against this complex and affinity purified with the immobilized peptide. A second peptide, with tyrosine residue added to the NH2-terminal of the above peptide, was synthesized and used as a standard and iodinated for preparation of the radioactive ligand. The assay is highly reproducible, sensitive, and specific for the COOH-terminal domain of the GLUT1 glucose transporter. It has no cross-reactivity with the other glucose-transporter isoforms GLUT2 and GLUT4. Furthermore, the results obtained with this radioimmunoassay on the number of glucose transporters in human erythrocytes were in good agreement with previous studies based on cytochalasin B binding, suggesting that this radioimmunoassay is able to quantify the number of glucose transporters. The assay is completed within 4 h and can be used for simultaneous measurement of GLUT1 in many samples. In addition, it can be applied to the measurement of GLUT1 in several types of tissue.
Diabetes 1991 Mar
PMID:Peptide-based radioimmunoassay specific for GLUT1 glucose transporter. 199 71

The potencies of several opioid agonists are reduced in diabetic animals and in animals made hyperglycemic via injections of glucose. In this report we examined the effects of streptozotocin-induced diabetes on the feeding responses to centrally administered opioid agonists with differing receptor selectivities. The selective mu receptor agonist Tyr-D-Ala-Gly-(Me)Phe-Gly-ol (DAGO) caused a larger increase in intake in diabetic rats than in controls. In both groups feeding responses were greater on the fourth day of daily injections than on the first day. The delta receptor agonist [D-Ser2,Leu5]-enkephalin-Thr6 (DSLET) stimulated intake in controls but not in diabetics. However, the elevated baseline and large variability in intake of the diabetics in this experiment prevent drawing a conclusion on diabetes-induced changes in the potency of this peptide. No differences between controls and diabetics were apparent in the feeding responses to U50, 488H, a selective kappa receptor agonist. These data suggest that diabetes may differentially affect the classes of opioid receptors or the binding of ligands to these receptors.
 ...
PMID:Effects of streptozotocin-induced diabetes on feeding stimulated by centrally administered opioid agonists. 254 90

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

A beta-variant hemoglobin, first misjudged as a marked elevation of Hb A1, was found in a 68-year-old Japanese female with diabetes mellitus. This hemoglobin was isolated by Bio-Rex 70 chromatography combined with chromatofocusing, and was found to be Hb Hope, beta 136(H14)Gly----Asp, by classical and high performance liquid chromatographic peptide mapping techniques. Intrinsic oxygen affinity of this hemoglobin was approximately one-third as compared with that of Hb A0. This property was still observed in the constituent beta subunits isolated. Effects of such allosteric effectors as H+ (at a fixed concentration of Cl-), anion (Cl-), 2,3-diphosphoglycerate and carbon dioxide were more or less depressed. Among others, a marked reduction in the carbamate effect should be noted in a structural interpretation of the functional modifications. Subunit cooperativity, on the contrary, was not different from that in Hb A0 (n = 2.8-2.9). Explanation of these altered functions were attempted on the basis of the altered structure. The reduced stability of Hb Hope is also described.
 ...
PMID:Hb Hope, beta 136(H14)Gly----Asp, in a diabetic Japanese female and its functional characterization. 270 63

Amyloid deposits occurring in the islets of Langerhans in patients with noninsulin-dependent diabetes mellitus and some insulinomas contain a 37-amino acid peptide that is structurally related to calcitonin gene-related peptide. We have identified three cDNA clones encoding islet amyloid polypeptide (IAPP) or diabetes-associated peptide (DAP) by oligonucleotide screening of a lambda gt10 human insulinoma cDNA library. Two of the three cDNAs contained a domain encoding IAPP/DAP but had an intron-like sequence in their 5' region. The other cDNA contained an open reading frame encoding an 89-amino acid precursor having a typical signal peptide followed by a small prohormone-like sequence containing within it the IAPP/DAP peptide bracketed at its NH2 and COOH termini by Lys-Arg and Gly-Lys-Arg, respectively. These data indicate that this amyloid peptide is generated by proteolytic processing similar to that for proinsulin and other islet prohormones and also that the peptide may be carboxyamidated. The isolation of cDNA clones having 5'-unprocessed intron-like sequences suggests that inefficient or alternative splicing of this mRNA occurred in the insulinoma.
 ...
PMID:An islet amyloid peptide is derived from an 89-amino acid precursor by proteolytic processing. 305 5

The skeletal muscle content of three rat proteinase inhibitors, a 1-proteinase inhibitor, contrapsin and a 1-cysteine proteinase inhibitor was measured by immunochemical techniques following streptozotocin-induced diabetes. When compared with normal rats, a 1-cysteine proteinase inhibitor and a 1-proteinase inhibitor levels remained essentially unchanged, whereas the content of rat contrapsin was reduced by nearly 80% after the onset of diabetes. Similarly, fasting of rats for three days resulted in a lowering of the levels of contrapsin in skeletal muscles. Under these conditions, levels of chymotrypsin-like activity (chymase) were increased by 150%, whereas the content of the trypsin-like, neutral proteinase was unchanged. Kinetic studies in vitro with Tosyl-Gly-Pro-Arg-4-nitroanilide as substrate showed no inhibition of the trypsin-like proteinase by a 1-proteinase inhibitor, while contrapsin inhibited the enzyme with a Ki value of 40nM. The changing pattern of these proteinases and their potential inhibitors (chymase/a 1-proteinase inhibitor and trypsin-like proteinase/contrapsin) may be a factor contributing to muscle wasting as observed in diabetes and fasting.
 ...
PMID:Changes in proteinase/proteinase inhibitor levels in rat skeletal muscle tissue during diabetes and fasting. 306 Jan 41


1 2 3 4 5 6 7 8 9 10 Next >>