Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011860 (type 2 diabetes)
 57,723 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A 49-year-old man with an 11 year history of NIDDM presented hypercalcemic and with acute on chronic renal failure. His only symptoms were mild anorexia and nausea. Four years previously he had been diagnosed as having lipoid pneumonia, with classical histological findings. On this admission, serum parathyroid hormone was suppressed and 1,25 dihydroxyvitamin D levels elevated. The cause of his hypercalcemia presumably was ectopic 1 hydroxylation of 25 hydroxyvitamin D in the chronic granulomata in his lungs. It should be emphasised that any chronic granulomatous disease, and not just sarcoidosis, may be a cause of hypercalcemia.
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PMID:Hypercalcemia and lipoid pneumonia. 263 65

Fasting plasma zinc levels were determined in 45 IDDM and in 40 NIDDM patients. Mean values were similar in both groups, but diabetic men showed a significantly higher plasma zinc (p less than 0.05) than diabetic women. In patients with diabetic nephropathy a lower zinc level was associated with decreased plasma albumin as compared to patients without complications (p less than 0.001). Neuropathy and macro-angiopathy were also associated with lower zincemia (p less than 0.05) but in the presence of normal albumin levels. In IDDM without nephropathy a significant positive correlation was found between plasma zinc and plasma glucose, albumin, branched chain amino acids and glutamine, while in NIDDM without nephropathy a significant positive correlation exists between plasma zinc and the amino acids glutamine, valine, histidine and lysine.
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PMID:Plasma zinc levels in diabetes mellitus: relation to plasma albumin and amino acids. 375 14

We have identified two types of mutants of Chinese hamster ovary cells in which the unique ADP-ribose attachment site in elongation factor 2 (EF-2) is altered, thereby rendering them resistant to diphtheria and Pseudomonas toxins (TOXR). The first is mutant in the gene for EF-2 and possesses a permanently altered, TOXR gene product. The second lacks a component of a posttranslational modification system that converts TOXR EF-2 to the toxin-sensitive (TOXS) state. We postulate that this modification system is involved in the conversion of a single histidine residue in EF-2 to the specific target of toxin-catalyzed ADP-ribosylation, the novel amino acid X. We have designated the second type MOD- mutants. The missing of nonfunctional component in the MOD- mutants can be restored by hybridizing them with either normal TOXS cells or with EF-2 structural gene mutants. The TOXR EF-2 from MOD- mutants is also converted to toxin sensitivity in vitro by incubation with extracts of TOXS or EF-2 gene mutant cells in the presence of an energy-generating system. Our results demonstrate that EF-2 can be synthesized and released from ribosomes in a toxin-resistant form and then converted to toxin sensitivity by posttranslational modification.
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PMID:Posttranslational modification of elongation factor 2 in diphtheria-toxin-resistant mutants of CHO-K1 cells. 692 55

Glucose-dependent insulinotropic polypeptide (GIP) plays an important role in the regulation of postprandial insulin secretion and proinsulin gene expression of pancreatic beta-cells. This study demonstrates the molecular cloning of a cDNA for the GIP-receptor from a human insulinoma lambda gt11 cDNA library. The cloned cDNA encoded a seven transmembrane domain protein of 466 amino acids which showed high homology (41%) to the human glucagon-like peptide 1 (GLP-1) receptor. Homology to the GIP receptor from rat or hamster was 79% and 81%, respectively. When transfected stably into fibroblast CHL-cells a high affinity receptor was expressed which coupled to the adenylate cyclase with normal basal cAMP and increasing intracellular cAMP levels under stimulation with human GIP-1-42 (EC50 = 1.29 x 10(-13) M). The receptor accepted only human GIP 1-42 (Kd = 1.93 +/- 0.2 x 10(-8) M) and porcine truncated GIP 1-30 (Kd = 1.13 +/- 0.1 x 10(-8) M) as high affinity ligands. At 1 microM, exendin-4 and (9-39)amide weakly reduced GIP-binding (25%) whereas secretin, glucagon, glucagon-like peptide-1, vasoactive intestinal polypeptide, peptide histidine-isoleucine, and pituitary adenylyl cyclase activating peptide were without effect. In transfected CHL cells, GIP-1-42 did not increase intracellular calcium. Northern analysis revealed one transcript of human GIP receptor mRNA with an apparent size of 5.5 kb. The exact understanding of GIP receptor regulation and signal transduction will aid in the understanding of the incretin hormone's failure to exert its biological action at the pancreatic B-cell in type II diabetes mellitus.
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PMID:Molecular cloning, functional expression, and signal transduction of the GIP-receptor cloned from a human insulinoma. 758 26

Human hexokinase (HK) II, a glucose phosphorylating enzyme in muscle tissue, plays a central role in glucose metabolism. Since reduced insulin-stimulated glucose uptake and reduced glucose-6-phosphate content in muscle have been demonstrated in pre-non-insulin-dependent diabetes mellitus (pre-NIDDM) and NIDDM subjects, we have examined the coding region of the HKII gene in NIDDM patients to determine whether these patients show genetic polymorphisms that are associated with or contribute to the disease. Single-strand conformational polymorphism analysis and nucleotide sequencing were initially performed on the entire coding region of the HKII gene of 38 insulin-resistant NIDDM patients and 5 healthy control subjects. This analysis revealed four missense mutations at codons 142 (Gln to His), 148 (Leu to Phe), 497 (Arg to Gln), and 844 (Arg to Lys) and an additional six exon polymorphisms that did not predict any change in amino acid composition of the protein. One homozygous and nine heterozygous carriers of the codon 142 mutation were found among the NIDDM patients. The mutations at codons 148, 497, and 844 were each found in one diabetic subject and only on one allele. There were no carriers of compound heterozygous mutations. A subsequent study of 301 patients with NIDDM and 151 healthy control subjects revealed no additional mutations at codons 148, 497, or 844. The total frequency of the mutated allele at codon 142 was 18.9% among the control subjects and 17.0% among the NIDDM patients (chi 2 = 0.56, P = 0.45).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Identification of four amino acid substitutions in hexokinase II and studies of relationships to NIDDM, glucose effectiveness, and insulin sensitivity. 788 23

A pedigree with maternally transmitted diabetes mellitus, deafness, and cardiomyopathy is described. A A-->G mutation at nucleotide pair 3243 in mitochondrial gene was detected by Apa I digestion of PCR amplified genomic DNA from 3 brothers and their mother. The proband, suffering from CHF, showed unique fine granular pattern of hyperechogenic cardiomyopathy as his brother and their mother did. Although he is recently treated with insulin, he was initially NIDDM treated by sulfonylurea. His urinary CPR excretion decreased gradually to as low as less than 10 micrograms/day in these 3 years. The insulin response to oral glucose was decreased in all other family members with the mutation. It is suggested that the defective insulin secretion exists in this family with the mutation and the progressive decrease in insulin secretion might resulted in IDDM in the proband.
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PMID:[A pedigree with maternally transmitted diabetes mellitus, deafness and cardiomyopathy]. 798 86

First, annual cost of electronic filing of medical images were calculated and compared with that of film storage in two hospitals under different conditions. Storage of medical images using a pixel size of 100 microns x 100 microns and 2-byte depth on the 130 mm, 650 MB magneto-optical disks costs with four times as much as the cost for film storage. However, 175 microns x 175 microns 12 bits combined with implementation of lossless compression would reduce the cost to a level equal to that for films storage. Doubled or tripled densities of MOD will improve the cost ever further. Second, the effectiveness of Hospital Information System/Radiological Information System (HIS/RIS) was evaluated. Examination time, film delivery time and the total turn-around time was markedly shortened by more than 23 hours on average. Our measurement method employing IC cards in pre-post HIS/RIS/PACS procedures is generally applicable to other hospitals. Third, to determine the optimal method of maximizing the efficacy of diagnostic imaging, 260 questionnaires were sent to the staff of 13 university hospitals. Every situation was described by both a radiologist and the physician who ordered the examination and received the reports and images. The level of technical efficacy and diagnostic accuracy of radiology strongly influenced the diagnostic thought processes of the physician.
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PMID:[Cost effectiveness of image diagnosis]. 913

As part of an ongoing search for susceptibility loci for NIDDM, we tested 19 genes whose products are implicated in insulin secretion or action for linkage with NIDDM. Loci included the G-protein-coupled inwardly rectifying potassium channels expressed in beta-cells (KCNJ3 and KCNJ7), glucagon (GCG), glucokinase regulatory protein (GCKR), glucagon-like peptide I receptor (GLP1R), LIM/homeodomain islet-1 (ISL1), caudal-type homeodomain 3 (CDX3), proprotein convertase 2 (PCSK2), cholecystokinin B receptor (CCKBR), hexokinase 1 (HK1), hexokinase 2 (HK2), mitochondrial FAD-glycerophosphate dehydrogenase (GPD2), liver and muscle forms of pyruvate kinase (PKL, PKM), fatty acid-binding protein 2 (FABP2), hepatic phosphofructokinase (PFKL), protein serine/threonine phosphatase 1 beta (PPP1CB), and low-density lipoprotein receptor (LDLR). Additionally, we tested the histidine-rich calcium locus (HRC) on chromosome 19q. All regions were tested for linkage with microsatellite markers in 751 individuals from 172 families with at least two patients with overt NIDDM (according to World Health Organization criteria) in the sibship, using nonparametric methods. These 172 families comprise 352 possible affected sib pairs with overt NIDDM or 621 possible affected sib pairs defined as having a fasting plasma glucose value of >6.1 mmol/l or a glucose value of >7.8 mmol/l 2 h after oral glucose load. No evidence for linkage was found with any of the 19 candidate genes and NIDDM in our population by nonparametric methods, suggesting that those genes are not major contributors to the pathogenesis of NIDDM. However, some evidence for suggestive linkage was found between a more severe form of NIDDM, defined as overt NIDDM diagnosed before 45 years of age, and the CCKBR locus (11p15.4; P = 0.004). Analyses of six additional markers spanning 27 cM on chromosome 11p confirmed the suggestive linkage in this region. Whether an NIDDM susceptibility gene lies on chromosome 11p in our population must be determined by further analyses.
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PMID:Genetics of NIDDM in France: studies with 19 candidate genes in affected sib pairs. 916 80

One form of maturity-onset diabetes of the young, MODY3, is characterized by a severe insulin secretory defect, compared with MODY2, a glucokinase-deficient diabetes. It has recently been shown that mutations of the gene encoding the transcription factor hepatocyte nuclear factor (HNF)-1 alpha cause MODY3. Because of the rapid progress to overt diabetes and the high prevalence of required insulin treatment in patients with MODY3, we screened the HNF-1 alpha gene for mutations in Japanese subjects with IDDM. Ten exons and flanking introns of the HNF-1 alpha gene in these subjects were amplified by polymerase chain reaction and direct sequencing of the products. Mutations were identified in three (5.5%) of the 55 unrelated subjects with IDDM. A missense mutation of R272H (replacement of Arg by His in codon 272) in the DNA binding domain of HNF-1 alpha was found in a subject who developed IDDM 1 year after diagnosis of NIDDM at 8 years of age. A frameshift mutation of P291 fsinsC (insertion of a C in a polyC tract around codon 291 for Pro), which would generate a mutant truncated protein of 340 amino acids, was found in a subject who started insulin treatment when hyperglycemia and ketonuria were noticed at 13 years of age. A missense mutation of R583G (replacement of Arg by Gly in codon 583) in the transactivation domain of HNF-1 alpha was found in a subject with sudden-onset IDDM at 20 years of age. None of these mutations were present in 100 nondiabetic subjects (200 normal chromosomes). These results indicate that the HNF-1 alpha gene defects could lead to the development of not only early-onset NIDDM but also IDDM, implicating the importance of subclassification of HNF-1 alpha-deficient IDDM from a classical type of autoimmune-based IDDM in Japanese.
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PMID:Identification of mutations in the hepatocyte nuclear factor (HNF)-1 alpha gene in Japanese subjects with IDDM. 931 63

One of Roberts' key contributions was his work demonstrating the applicability of several ecological rules to human populations (Roberts [1953] Am. J. Phys. Anthropol. 11:533-558; [1978] Climate and Human Variability, 2nd ed., Menlo Park, CA: Cummings). His finding that average body weight systematically covaries with mean annual temperature was widely taken as confirmation of Bergmann's rule for humans. More recently his findings on weight and temperature have been extended and confirmed (Ruff [1994] Yrbk. Phys. Anthropol. 37:65-407; Katzmarzyk and Leonard [1995] Hum Biol Council Program Abstracts 132) although the strength of the association may be decreasing when considering more recent surveys (Katzmarzyk and Leonard [1995]). Roberts noted in 1953 that Oceanic populations may be somewhat of an exception to Bergmann's rule, and we propose that Neel's ([1962] Am. J. Hum. Genet. 14:353-362) thrifty genotype model may account for some of the deviation from predicted weights among these populations. We provide an updated version of the thrifty genotype model, suggesting that selection for energetic efficiency may have occurred for some Oceanic populations during the voyaging to and settlement of their island homes. Under conditions of modernization the thrifty genotype may be manifesting as high rates of obesity and NIDDM among Polynesians and Micronesians. First, using measurements of adult male weight from 19 Oceanic populations, we demonstrate the extreme nature of their deviation from predicted weight based on Roberts' regression of weight on mean annual temperature. Next, we regress the deviations from predicted weight on NIDDM prevalence for these 19 populations, producing a highly significant regression (R2 = 0.46; P < 0.001), consistent with expectations if the thrifty genotype is responsible for the high weights.
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PMID:Bergmann's rule and the thrifty genotype. 938 27


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