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)

We studied the molecular characteristics of three naturally occurring variants in the human apolipoprotein B (apoB) signal peptide, their frequencies in non-insulin-dependent diabetic and random populations, and their association with several measures of lipid and carbohydrate metabolism. In a random sample of 197 French whites, there were two common alleles, 5'beta SP-24 and 5'beta SP-27, with frequencies of 0.35 and 0.65, respectively. In a random sample of 181 Mexican Americans, there was an additional allele, 5'beta SP-29, with a frequency of 0.03. DNA sequence analysis indicated that the signal peptide alleles consisted of the following: 5'beta SP-29 encoded 29 amino acids in the signal peptide containing two copies of the sequence CTG GCG CTG encoding Leu-Ala-Leu and a consecutive run of eight Leu-encoding codons; 5'beta SP-27 encoded 27 amino acids with a run of only six Leu codons; 5'beta SP-24 encoded 24 amino acids and contained a single copy of CTG GCG CTG and a run of six Leu codons. In the sample of French whites, average apoAI and glucose levels were significantly different among signal peptide genotypes. 5'beta SP-24/24 homozygotes had higher apoAI levels than the two other signal peptide genotypes (1.59 vs. 1.42 g/L, respectively). Heterozygous 5'beta SP-24/27 individuals had the highest glucose levels. In the random sample of Mexican Americans, average glucose levels were also significantly different among signal peptide genotypes. However, the rank order of average glucose levels was not the same between the two samples.(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes 1991 Nov
PMID:Signal peptide-length variation in human apolipoprotein B gene. Molecular characteristics and association with plasma glucose levels. 193 12

Insulin-releasing effects of glucagon-like peptides, glucagon and various nutrients were examined using tumour cells from a freshly resected human insulinoma and RINm5F cells. Insulin release by human insulinoma cells or RINm5F cells was not affected by 16.7 mM glucose. Both cell types exhibited secretory responses to 20 mM alanine, 25 mM K+ and 7.6 mM Ca2+. Insulin release by human insulinoma cells was enhanced at 2 x 10(-7) M by glucagon, GLP-1[1-37], GLP-1[7-36] and its N- and C-terminal fragments GLP-1[7-14] and GLP-1[31-37]. The intact peptides (2 x 10(-6)-2 x 10(-12) M) also stimulated insulin release by RINm5F cells, but neither of the fragments enhanced secretion. The cyclic AMP content of human insulinoma cells and RINm5F cells was increased by glucagon. GLP-1[7-36] (2 x 10(-8)-2 x 10(-10) M) increased cyclic AMP in RINm5F cells, but no additional effects were noted in these or human insulinoma cells. These results suggest that GLP-1[7-36] stimulates insulin release by a direct action on human and rat B-cells, partly involving modulation of intracellular cyclic AMP.
Diabetes Res 1990 Feb
PMID:Stimulatory effects of glucagon-like peptides on human insulinoma cells and insulin-releasing clonal RINm5F cells. 196 28

The human leukocyte antigens (HLA) are implicated in the genetic susceptibility to a large number of diseases. Some of the diseases associated with HLA class II are related to specific amino acids or epitopes of the domain of the HLA class II molecule that is distal to the membrane. In man, selective immunoglobulin A deficiency is the most common immunodeficiency, frequently resulting in recurrent sino-pulmonary infections and gastro-intestinal disorders. Associations have been described with HLA class I, and to a lesser extent with different class II alleles, which might indicate that they share some common feature. Here we study 95 IgA-D patients and find positive associations with three DR-DQ haplotypes and a strong negative association with a fourth haplotype. Comparison of the sequences of the polymorphic amino-terminal domain of the DQ beta chain showed that the three 'susceptibility' haplotypes all had a neutral alanine or valine at position 57. The 'protective' allele had the negatively charged aspartic acid at this position (Asp57). Codon 57 of the HLA-DQ beta chain has been implicated in the susceptibility to insulin-dependent diabetes mellitus. Our data suggest that the same amino acid position could possibly also influence susceptibility and resistance to selective immunoglobulin A deficiency.
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PMID:Different amino acids at position 57 of the HLA-DQ beta chain associated with susceptibility and resistance to IgA deficiency. 197 29

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 effects of feeding corn or hydrogenated coconut oil on various parameters of glucose metabolism in prediabetic BHE rats was studied. Weanling rats were fed a 6% fat-64% sucrose diet. At seven weeks of age, the rats were weight matched within diet treatments. Half of the rats were injected with 6(3)H/U14C glucose while their weight matched counterparts were injected with U14C alanine and 3HOH. Diet had no effect on glucose mass, glucose space, hepatic glycogen or blood glucose levels. However, diet did affect other parameters. HCO fed rats had higher fractional irreversible glucose turnover rates, fractional glucose carbon recycling, hepatic fatty acid synthesis rates, adipose fatty acid synthesis rate, lower muscle glycogen and lower rates of incorporation of glucose into muscle glycogen than corn oil fed rats. These differences in glucose flux explain the maintenance of glucose homeostasis in these prediabetic coconut oil fed rats in the face of increased fatty acid and glucose synthesis.
Diabetes Res 1990 Jan
PMID:Glucose turnover in BHE rats fed EFA deficient hydrogenated coconut oil. 209 95

The relation of urea synthesis rate to blood alanine concentration was assessed in seven healthy controls and in 18 patients with insulin-dependent diabetes mellitus (HbAlc = 8.4 +/- 1.0% (mean +/- SD)). Following an overnight fast alanine was infused at 2 mmol h-1 kg-1 body weight. The hourly rate of urea synthesis was determined as the urinary excretion of urea corrected for accumulation of urea in total body water and intestinal hydrolysis. The functional hepatic nitrogen clearance, i.e. the relation of urea synthesis rate to blood alanine concentration, was calculated as the slope of linear regression of urea synthesis rates on blood alanine concentrations. Fasting glucagon concentrations were 85 +/- 26 ng l-1 in controls and 161 +/- 35 ng l-1 (P less than 0.01) in patients. The functional hepatic nitrogen clearances were 21.8 +/- 4.4 l h-1 in controls and 44.7 +/- 12.4 l h-1 (P less than 0.001) in patients. By multiple step-wise linear regression analysis the functional hepatic nitrogen clearance was found to correlate independently to fasting glucagon concentration, duration of diabetes, change in blood glucose and insulin following alanine infusion (r2 = 0.74). In a simple linear regression analysis the functional hepatic nitrogen clearance correlated strongly to fasting glucagon concentration (r2 = 0.54). In conclusion the kinetics of urea synthesis in insulin-dependent diabetes is changed in favour of increased conversion of alanine-N to urea-N at any blood amino acid concentration. The increased FHNC correlates strongly with hyperglucagonaemia.
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PMID:Increased hepatic efficacy of urea synthesis from alanine in insulin-dependent diabetes mellitus. 210 34

To assess the role of muscle and liver in the pathogenesis of postprandial hyperglycemia in non-insulin-dependent diabetes mellitus (NIDDM), we administered an oral glucose load enriched with [14C]glucose to 10 NIDDM subjects and 10 age- and weight-matched nondiabetic volunteers and compared muscle glucose disposal by measuring forearm balance of glucose, lactate, alanine, O2, and CO2 (with forearm calorimetry). In addition, we used the dual-lable isotope method to compare overall rates of glucose appearance (Ra) and disappearance (Rd), suppression of endogenous glucose output, and splanchnic glucose sequestration. During the initial 1-1.5 h after glucose ingestion, plasma glucose increased by approximately 8 mM in NIDDM vs. approximately 3 mM in nondiabetic subjects (P less than 0.01); overall glucose Ra was nearly 11 g greater in NIDDM than nondiabetic subjects (45.1 +/- 2.3 vs. 34.4 +/- 1.5 g, P less than 0.01), but glucose Rd was not significantly different in NIDDM (35.1 +/- 2.4 g) and nondiabetic (33.3 +/- 2.7 g) subjects. The greater overall glucose Ra of NIDDM subjects was due to 6.8 g greater endogenous glucose output (13.7 +/- 1.1 vs. 6.8 +/- 1.0 g, P less than 0.01) and 3.8 g less oral glucose splanchnic sequestration of the oral load (31.4 +/- 1.5 vs. 27.5 +/- 0.9 g, P less than 0.05). Although glucose taken up by muscle was not significantly different in NIDDM and nondiabetic subjects (39.3 +/- 3.5 vs. 41.0 +/- 2.5 g/5 h), a greater amount of the glucose taken up by muscle in NIDDM was released as lactate and alanine (11.7 +/- 1.0 vs. 5.2 +/- 0.3 g in nondiabetic subjects, P less than 0.01), and less was stored (11.7 +/- 1.3 vs. 16.9 +/- 1.5 g, P less than 0.05). We conclude that increased systemic glucose delivery, due primarily to reduced suppression of endogenous hepatic glucose output and, to a lesser extent, reduced splanchnic glucose sequestration, is the predominant factor responsible for postprandial hyperglycemia in NIDDM.
Diabetes 1990 Nov
PMID:Contribution of abnormal muscle and liver glucose metabolism to postprandial hyperglycemia in NIDDM. 212 68

To study insulin action on intermediary metabolism in relation to glucose disposal in Type 1 (insulin-dependent) diabetes, 29 patients and 15 control subjects underwent sequential euglycemic clamps (insulin infusion rates 0.5, 1.0, 2.0 and 5.0 mU.kg-1.min-1 in 2 hour periods). Dose-response curves were constructed for insulin-stimulated glucose disposal. Metabolite profiles were determined in the basal state, and during submaximal (+/- 80 mU/l) and maximal (greater than 500 mU/l) insulinaemia. For at least 11 hours preceding the study, blood glucose levels were maintained between 4 and 10 mmol/l in the patients. In the basal state, when at matched glycemia hepatic glucose production is known to be similar in patients and control subjects, glucose, glycerol, free fatty acids and glucagon were comparable, whereas differences were found for alanine (-29%, diabetic vs. control subjects), lactate (-24%), acetoacetate (+270%), 3-hydroxybutyrate (+260%) and insulin (+210%; all p less than 0.02). At submaximal (+/- 80 mU/l) and maximal (greater than 500 mU/l) insulin levels, metabolite levels were comparable, except alanine (-20% diabetic vs. control subjects, p less than 0.001). Glucose disposal rates, however, were decreased in patients at submaximal insulin levels (ED50 73 +/- 10 vs. 54 +/- 4 mU/l in control subjects, p less than 0.01 whereas maximal glucose disposal was similar (61 +/- 3 vs. 65 +/- 3 mumol.kg-1.min-1). In conclusion, in Type 1 diabetes: (a) changes in basal levels of intermediary metabolites were present, despite 11 hours of antecedent euglycemia; (b) in contrast to glucose disposal at submaximal insulinaemia, no major difference existed in insulin's efficacy on intermediary metabolism.
Diabetes Res 1990 Sep
PMID:Insulin resistance in type 1 (insulin-dependent) diabetes: dissimilarities for glucose and intermediary metabolites. 213 95

Tissue culture for one or seven days of pancreatic islets isolated from 21-day old fetal rats was found to be associated with a marked increase in the oxidation of L-(U-14C) glutamine by intact islets and in the activity of both alanine-glutamate and aspartate-glutamate transaminases as well as glutamate dehydrogenase in islet homogenates. This coincided with an increase in the relative amount of mitochondrial DNA. The activities of glucose-phosphorylating enzymes (hexokinase and glucokinase), glyceraldehyde-3-phosphate dehydrogenase and lactate dehydrogenase were less markedly increased during the culture period than those of enzymes involved in amino acid catabolism and located, in part at least, in mitochondria. The combined data suggest that the functional maturation of fetal islets during the culture period is associated with and may be attributable to a preferential maturation of their mitochondria.
Diabetes Res 1990 Apr
PMID:Maturation of fetal rat islet cells in vitro during tissue culture is associated with increased mitochondrial function. 213 6

Glomerular hyperfiltration is a characteristic feature of insulin-dependent diabetes. We examined the relative roles of renal size, as well as glycemic parameters (HbA1c, glycosylated albumin, plasma glucose) in addition to growth hormone, somatomedin C, beta-hydroxybutyrate, alanine, and glycerol in determining the glomerular filtration rate (GFR). Sixty-two insulin-dependent patients with normal urinary albumin excretion rates (AER less than 15 micrograms/min), who were less than 50 years of age, were included in the study. Data were subjected to multiple regression analysis with GFR as a dependent variable. Renal volume was the primary statistical determinant of hyperfiltration, but HbA1c also significantly correlated with GFR. No correlation was found with glycosylated albumin or blood glucose, but RPF correlated strongly with GFR, and borderline correlation was found between renal volume and HbA1c. Renal hyperfiltration, defined as a GFR greater than 150 ml/min, was found in approximately 50% of patients with HbA1c values greater than 9.5%. Other studies suggest that such patients have a much higher risk of developing clinically evident diabetic nephropathy over the ensuing years. Renal volume appears to be the major determinant of GFR, but long-term metabolic control, as evidenced by the level of HbA1c, also contributes, partly independent of renal volume. Short-term metabolic control, as evaluated by blood glucose and serum-fructosamine, did not correlate with GFR. We suggest that exact determination of GFR and renal volume should be included in long-term prospective controlled intervention trials in patients with insulin-dependent diabetes mellitus (IDDM).
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PMID:Renal and glycemic determinants of glomerular hyperfiltration in normoalbuminuric diabetics. 215 Dec 27


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