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)

Spectral analysis of spin-echo 1H magnetic resonance spectroscopy (MRS) data has revealed differences in the metabolic profiles of maternal and fetal plasma and placental extracts. Resonances from low-molecular weight components of the normal maternal and fetal plasma were attributed to glucose, lactate, creatine, citrate, amino acids and ketone bodies. There were also signals from lipoprotein molecules associated with lipid-transporting moeties contained in the plasma. The placental extract showed a similar composition to the plasma samples however the spectra were dominated by a large signal attributed to betaine, there was also an absence of signals from citrate, acetoacetate, acetone and lipoproteins. Diabetes caused profound changes in all tissue types indicating high levels of glucose and ketogenic activity. In both the maternal and fetal plasma there were increases in glucose, ketone bodies and valine in the diabetic rats, increases in lactate and alanine were confined to the fetal plasma and placenta. This study indicates that diabetes causes major changes in the composition of fetal plasma which in turn could interfere with the development of the fetus.
Diabetes Res 1994
PMID:A comparison of the metabolic profiles of fetal and maternal plasma and placenta in normal and diabetic rats by 1H magnetic resonance spectroscopy. 762 18

Diabetes is known to cause impaired endothelium-dependent relaxation of blood vessels. The purpose of this study was to determine whether this endothelial dysfunction is a permanent defect or is reversible after acute arginine supplementation in vitro or by surgical intervention in vivo using syngeneic pancreatic islet transplantation. Lewis rats were injected with streptozotocin to induce diabetes and were studied either 8 or 12 weeks later. Another group received syngeneic islets via intraportal injection at 8 weeks of diabetes and were allowed to become euglycemic for 4 weeks before study. Thoracic aortic rings were tethered in isolated muscle baths, contracted with a submaximal concentration of norepinephrine, and challenged with either the endothelium-dependent vasodilator acetylcholine or the endothelium-independent vasodilator nitroglycerin. Relaxation to acetylcholine (but not nitroglycerin) was reduced in both 8- and 12-week diabetic rings compared with age-matched control rings. Preincubation of diabetic rings in vitro with L-arginine (but not D-arginine) restored relaxation to acetylcholine to normal to rings from 8-week but not 12-week diabetic animals. Plasma basic amino acids (arginine, lysine, and histidine) were reduced by diabetes, whereas other neutral or acidic amino acids were unchanged (phenylalanine, proline, and glutamate), reduced (serine, cysteine, threonine, tyrosine, tryptophan, and aspartate), or elevated (isoleucine, leucine, and valine). Islet transplantation restored to normal the changes in plasma amino acids. Elevation in blood glucose and total glycosylated hemoglobin in diabetic animals was normalized after islet transplantation. Furthermore, islet transplantation completely restored the defective endothelium-dependent relaxation to acetylcholine in diabetic rings.(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes 1995 Sep
PMID:Syngeneic pancreatic islet transplantation reverses endothelial dysfunction in experimental diabetes. 765 36

Renal hypertrophy in diabetes is accompanied by an increase in kidney protein content, which reflects an imbalance between protein synthesis and degradation. This study determines whether altered cellular protein degradation contributes to the imbalance. Diabetes was induced in rats with streptozotocin (55 mg/kg/ip). After 2 or 4 days of diabetes, kidney weight and protein content were measured. Over the 4 days, despite a loss in body weight, kidney wet weight increased by 35% and protein content by 37% in the diabetic rats. Treatment with insulin prevented this increase. Long-lived protein degradation was measured in isolated proximal tubules prelabeled with (14C)valine in vivo. Two days after streptozotocin, protein degradation was depressed by 19% (P < 0.05) and by the fourth day by 27% compared with that in nondiabetic controls (2.6% +/- 0.2 versus 1.9 +/- 0.1% degraded/h; P < 0.01). This was accompanied by a similar diabetes-induced decrease in proximal tubule cathepsin B and L activity. Accordingly, this study provides direct evidence that, in diabetes, tubular cell protein breakdown is depressed and suggests that altered lysosomal cathepsin activity may contribute to this effect. Depressed proteolysis likely contributes to the increase in kidney protein content and hence to diabetic renal hypertrophy.
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PMID:Tubular cell protein degradation in early diabetic renal hypertrophy. 802 32

Glut2, the facilitative glucose transporter isoform expressed in pancreatic beta cells, is believed to play a role in glucose-stimulated insulin secretion. Two polymorphisms that result in amino acid substitutions have been reported in the human Glut2 gene (Tanizawa, Y., Riggs, A. C., Chiu, K. C., Janssen, R. C., Bell, D. S. H., Go, R. P. C., Roseman, J. M., Acton, R. T., and Permutt, M. A. (1994) Diabetologia 37, 420-427). A threonine 110-->isoleucine substitution was present at equal frequency in diabetic and control populations, and a valine 197-->isoleucine substitution was discovered in a single allele of a patient with non-insulin-dependent diabetes. The effect of these amino acid changes on glucose transport activity was tested by expression of the mutant proteins in Xenopus oocytes. The polymorphism at threonine 110 had no effect on the expression of Glut2 protein or the uptake of 2-deoxyglucose. Remarkably, however, the highly conservative valine 197-->isoleucine amino acid change abolished transport activity of the Glut2 transporter expressed in Xenopus oocytes. This represents the first known dysfunctional mutation in a human facilitative glucose transporter protein. The presence of this mutation in a diabetic patient suggests that defects in Glut2 expression may be causally involved in the pathogenesis of non-insulin-dependent diabetes.
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PMID:A mutation in the Glut2 glucose transporter gene of a diabetic patient abolishes transport activity. 802 28

To better understand abnormal insulin production (IP) in states of carbohydrate intolerance, insulin release was quantified following equimolar (2.4 mmol/kg) infusions of glucose, arginine, and valine in healthy subjects ([HS] age, 45 +/- 3 years; body mass index [BMI, kg/m2], 26.3 +/- 2.4; means +/- SEM), obese subjects with impaired glucose tolerance ([IGT] age, 43 +/- 5 years; BMI, 35.4 +/- 2.4), and non-obese patients with chronic non-insulin-dependent diabetes mellitus ([NIDDM] age, 55 +/- 3 years; BMI, 26.4 +/- 1.4; duration of disease, 13 +/- 3 years). There were eight subjects per group. Incremental IP (metabolic clearance rate of C-peptide [MCRCP] x total incremental area under the curve of plasma C-peptide [AUCCP], pmol/kg) following substrate infusion was as follows: glucose: HS, 227 +/- 14; IGT, 1,050 +/- 184 (P < .001 v HS); NIDDM, 114 +/- 27 (P < .001 v HS); arginine: HS, 139 +/- 23; IGT, 488 +/- 106 (P < .01 v HS); NIDDM, 206 +/- 47; and valine: HS, 21 +/- 7; IGT, 32 +/- 10; NIDDM, 54 +/- 12 (P < .01 v HS). The fractional clearance rate ([FCR] k, %/min) was impaired in IGT and NIDDM for glucose (HS, 3.9 +/- 0.4; IGT, 2.3 +/- 0.3 [P < .01 v HS]; NIDDM, 1.4 +/- 0.1 [P < .001 v HS]), arginine (2.4 +/- 0.1; 1.9 +/- 0.2 [P < .01 v HS]; 1.9 +/- 0.2 [P < .01 v HS]), and valine (0.95 +/- 0.06; 0.65 +/- 0.09 [P < .05 v HS]; 0.74 +/- 0.1 [P < .05 v HS]).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Insulin production following intravenous glucose, arginine, and valine: different pattern in patients with impaired glucose tolerance and non-insulin-dependent diabetes mellitus. 813 89

Obesity-associated hyperaminoacidemia is traditionally interpreted as a consequence of insulin resistance. We performed two different experiments to investigate the effects of both obesity-associated insulin resistance and the insulin resistance of non-insulin-dependent diabetes mellitus (NIDDM) on amino acid metabolism. In the first experiment, we measured postabsorptive amino acid concentrations and their decline in response to an oral carbohydrate load in 19 obese nondiabetic women and 19 normal-weight nondiabetic controls. Obese subjects were more resistant to insulin with respect to its effects on glucose metabolism than normal-weight controls, as calculated by the method described by Matthews. However, postabsorptive plasma concentrations of the so-called large neutral amino acids (LNAA), namely phenylalanine, tyrosine, valine, leucine, and isoleucine, and their decrease in response to carbohydrate consumption were similar in both groups. In the second experiment, we compared the decrease of plasma concentrations of LNAA during a euglycemic, hyperinsulinemic clamp in obese subjects with and without NIDDM. Peripheral glucose uptake (PGU) was more impaired in NIDDM subjects compared with obese controls. Furthermore, hepatic glucose production (HGP) was less attenuated by insulin infusion in NIDDM than in control subjects. Postabsorptive plasma LNAA concentrations were not different in the two groups. Values obtained in either group were not different from the postabsorptive concentrations in the normal-weight control subjects of experiment 1. All amino acid levels decreased substantially in response to insulin infusion. The magnitude of the decrease was not significantly different in the two groups, except for a slightly greater decrease of the plasma isoleucine concentration in obese control subjects.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Insulin-induced decline of plasma amino acid concentrations in obese subjects with and without non-insulin-dependent diabetes. 817 54

To investigate if alterations of the amino acid metabolism may play a more important role in the etiology of diabetic microangiopathy than hitherto recognized, free amino acids in plasma were measured by means of high-performance liquid chromatography (HPLC) in healthy individuals (REF) and patients with insulin-dependent diabetes mellitus (IDDM) and non-insulin-dependent diabetes mellitus (NIDDM). Isoleucine and leucine in IDDM were within normal limits, whereas they were significantly higher in NIDDM (P < 0.01 and P < 0.001, respectively). This was not due to age differences. In order to evaluate the impact of insulin on amino acid metabolism, amino acids were also measured in pregnant women (PREG) undergoing glucose tolerance tests as a screening for pregnancy diabetes and in patients with polycystic ovary syndrome (PCO) undergoing euglycemic insulin clamp tests. Insulin considerably reduced the amino acid concentration. Isoleucine and leucine were particularly depressed. On the whole there was strong covariance between the three branched-chain amino acids, isoleucine, leucine, and valine (P < 0.0001). There was no covariance between amino acid and glucose or HbA1c concentrations. A protein meal strongly stimulated insulin production (+55 mIU/liter), whereas a galactose meal revealed only a minor increase in insulin response (+12 mIU/liter) in contrast to a tolerance test with the same amount of glucose (+67 mIU/liter). It is concluded that disturbed amino acid metabolism may be a more important causative factor in the etiology of diabetic microangiopathy than hitherto recognized and, in addition, that this may affect the therapeutic approach in both IDDM and NIDDM patients.
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PMID:Effects of insulin on free amino acids in plasma and the role of the amino acid metabolism in the etiology of diabetic microangiopathy. 834 81

One of the characteristics of non-insulin-dependent diabetes mellitus (NIDDM) is the presence of insulin resistance. Most NIDDM patients have a normal sequence of the insulin receptor, indicating that, if insulin-receptor mutations contribute to the development of NIDDM, they will be present only in a minor fraction of the NIDDM population. The goal of the present study was to examine whether insulin-receptor mutations contribute to the development of NIDDM. We examined 161 individuals with NIDDM and 538 healthy controls from the population-based Rotterdam study for the presence of mutations in the insulin-receptor gene by SSCP. A heterozygous mutation changing valine-985 into methionine was detected in 5.6% of diabetic subjects and in 1.3% of individuals with normal oral glucose tolerance test. Adjusted for age, gender, and body-mass index, this revealed a relative risk for diabetes of 4.49 (95% confidence interval 1.59-12.25) for Met-985 carriers. When the total study group was analyzed, the prevalence of the mutation increased with increasing serum glucose levels (test for trend P < .005). We conclude that the Met-985 insulin-receptor variant associates with hyperglycemia and represents a risk factor for NIDDM.
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PMID:Association of the insulin-receptor variant Met-985 with hyperglycemia and non-insulin-dependent diabetes mellitus in the Netherlands: a population-based study. 890 Feb 42

4 patients of two families with congenital persistent hyperthyroidism without detectable autoantibodies are reported. The members of the first family affected by hyperthyroidism, i.e. the mother and her two children, showed a germline mutation, a transition of GCC to GTC in the genomic DNA of the TSH receptor, leading to an exchange of alanine by valine at the position 623. The mother was thyroidectomized at two times because of recurrent nodular goiter. The third child of a healthy second family showed a transition of AGC to AAC leading to an exchange of serine by asparagine at the position 505 of the TSH receptor. The mutation of family 1, as a somatic point mutation leading to autonomous thyroid adenoma, has originally been demonstrated to constitutively activate TSH independent cAMP accumulation. The functional tests of the TSH receptor gen mutation, detected in family 2, are ongoing, but an exchange of serine by arginine at the same position has been shown to lead to constitutively active cAMP accumulation. The cases of congenital hyperthyroidism in the first family lead to a reduction of the birth weight and head circumference and to a neonatal but not fetal tachycardia. Bone age of both children was accelerated by one year. In contrast to that, congenital hyperthyroidism of the second family lead to more marked signs of intrauterine hyperthyroidism. The mother observed marked symptoms of fetal and neonatal hyperthyroidism. The bone age at a chronological age of 6 months was 4-6 years and the neonate showed a mild exophthalmus. We conclude, that congenital hyperthyroidism due to constitutively activating TSH receptor mutations has to be considered, if hyperthyroidism is not transient but persistent, and the parameters of autoimmunity are absent. Constitutively active TSH receptor germline mutations lead to different degrees of congenital hyperthyroidism. In contrast to patients with Graves' disease, more aggressive means of treatment like total thyroidectomy and/or radiation seem to be recommendable in cases with severe hyperthyroidism to control the disease.
Exp Clin Endocrinol Diabetes 1996
PMID:Mutations of the TSH receptor as cause of congenital hyperthyroidism. 898 Oct 19

Hydroxycarboxylic acids in urine of patients with non-insulin-dependent diabetes mellitus and of healthy subjects are analyzed as 2-nitrophenylhydrazides by an improved high-performance liquid chromatographic method which has advantages with respect to resolution and analysis time. Variations in levels of hydroxycarboxylic acids, originated from the metabolism of valine, leucine and isoleucine, have been described in the diabetic patients who have good and poor metabolic controls. The sum of the hydroxycarboxylic acids in both groups of diabetic patients was significantly increased compared with the values of the healthy subjects. Statistically significant difference was present between the two groups. In the whole group of diabetic patients, the sum of the hydroxycarboxylic acids correlated with fasting plasma glucose or hemoglobin A1c (r = 0.548, P < 0.01 and r = 0.629, P < 0.01, respectively). These results suggest that the relevance of these abnormalities may be used as an index of metabolic control in diabetic patients.
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PMID:High-performance liquid chromatographic measurements of urinary hydroxycarboxylic acids as an index of the metabolic control in non-insulin-dependent diabetic patients. 899 47


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