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

The effects of insulin deficiency on nitrogen metabolism in muscle and liver have been extensively studied with recent in vivo demonstration of impaired protein synthesis in rats with streptozotocin-induced diabetes. Despite the significant contribution of small intestinal mucosa to overall protein metabolism, the effects of insulin deficiency on intestinal protein synthesis have not been completely defined. We studied the effects of streptozotocin-induced diabetes on total protein synthesis by small intestinal mucosa and on synthesis of a single enzyme protein of the enterocyte brush-border membrane sucrase-isomaltase. We used the flooding-dose technique of McNurlan, Tomkins, and Garlick (Biochem. J. 178: 373-379, 1979) to minimize the difficulties of measuring specific radioactivity of precursor phenylalanine and determined incorporation into mucosal proteins and sucrase-isomaltase 20 min after injection of the labeled amino acid. Diabetes did not alter mucosal mass as determined by weight and content of protein and DNA during the 5 days after injection of streptozotocin. Increased rates of sucrase-isomaltase synthesis developed beginning on day 3, and those of total protein developed on day 5. Thus intestinal mucosal protein synthesis is not an insulin-sensitive process.
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PMID:Intestinal mucosa in diabetes: synthesis of total proteins and sucrase-isomaltase. 352 21

A nutritive sweetener, aspartame (L-aspartyl-L-phenylalanine methylester) was administered orally to normal controls and diabetic patients in order to evaluate effects on blood glucose, lipids and pancreatic hormone secretion. An oral glucose tolerance test was also performed in the same subjects as a control study of aspartame administration. In 7 normal controls and 22 untreated diabetics, a single dose of 500 mg aspartame, equivalent to 100 g glucose in sweetness, induced no increase in blood glucose concentration. Rather, a small but significant decrease in blood glucose was noticed 2 or 3 h after administration. The decrease in blood glucose was found to be smallest in the control and became greater as the diabetes increased in severity. No significant change in blood insulin or glucagon concentration during a 3-h period was observed in either the controls or the diabetics. The second study was designed to determine the effects of 2 weeks' continuous administration of 125 mg aspartame, equal in sweetness to the mean daily consumption of sugar (20-30 g) in Japan, to 9 hospitalized diabetics with steady-state glycemic control. The glucose tolerance showed no significant change after 2 weeks' administration. Fasting, 1 h and 2 h postprandial blood glucose, blood cholesterol, triglyceride and HDL-cholesterol were also unaffected. From these and other published results, aspartame would seem to be a useful alternative nutrient sweetener for patients with diabetes mellitus.
Diabetes Res Clin Pract 1986 Apr
PMID:Glucose tolerance, blood lipid, insulin and glucagon concentration after single or continuous administration of aspartame in diabetics. 352 47

In vitro studies have suggested that ascorbate or dehydroascorbate share with glucose the same tissue-transport carrier. To determine if ascorbic acid or its oxidized form can inhibit tissue uptake of glucose, the brain uptake index (BUI) and muscle uptake index of glucose were determined by single arterial injection tissue-sampling technique. The injectate was either buffered Ringer's solution with varying concentrations of ascorbate, dehydroascorbate (pH 7.4), or 70% serum from individuals on vitamin C supplements. Ascorbic acid over a wide range of concentrations (0-10,000 mg/L) did not reduce the BUI. Ascorbic acid reduced BUI from the control value of 33 +/- 3.2 to 20.1 +/- 2.2% (P less than .01) only at 100,000 mg/L; this effect was probably secondary to osmotic disruption of blood-brain barrier. In contrast, dehydroascorbate inhibited the BUI of glucose from baseline value of 32.8 +/- 1.1 to 10.7 +/- 0.67%, with an estimated Ki of 13.0 mM. Masseter muscle glucose uptake was not significantly altered over a wide range of ascorbate or dehydroascorbate concentrations in the injectate. Dehydroascorbate (7500 mg/L) did not significantly reduce the BUI of [14C]phenylalanine (55.2 +/- 4.4 vs. 62.1 +/- 4.2% in controls). When serum from six individuals on calcium ascorbate (3-5 g/day) was compared with that of nine controls, the BUI was not different (19.3 +/- 1.7 vs. 19.3 +/- 1.1%). Similarly, supplementing the diet of eight healthy volunteers with 1 g calcium ascorbate for 8 days did not alter the BUI of glucose.(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes 1987 Sep
PMID:Effect of ascorbate and dehydroascorbate on tissue uptake of glucose. 360 94

Chronic (10-day) diabetes was associated with increased metabolic flux through phenylalanine hydroxylase in isolated liver cells. This flux was stimulated by 0.1 microM-glucagon, but not by 10 microM-noradrenaline; 0.1 microM-insulin affected neither basal nor glucagon-stimulated flux. The increased rate of phenylalanine hydroxylation in diabetes was accompanied by parallel increases in enzyme activity (as measured with artificial cofactor) and immunoreactive-enzyme-protein content. In contrast with total protein synthesis, which decreased, phenylalanine hydroxylase synthesis persisted at the control rate in cells from diabetic animals. These findings are discussed in relation to the hormonal regulation of the hydroxylase and the known metabolic consequences of chronic diabetes.
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PMID:The effect of experimental diabetes on phenylalanine metabolism in isolated liver cells. 388 93

The effects of aspartame (L-aspartyl-L-phenylalanine methyl ester) on plasma glucose and insulin levels were investigated in diabetic rats and patients with non-insulin-dependent diabetes mellitus. The oral administration of 0.45 mg aspartame per 100g body weight, which is equivalent to 150 mg of glucose in sweetness, to streptozotocin-induced diabetic rats had no effect on the plasma glucose or insulin levels. Also, 225 mg oral aspartame loading, which is equivalent to 75 g of glucose in sweetness, to patients with non-insulin-dependent diabetes mellitus did not increase plasma glucose or insulin levels, although 75 g of oral glucose loading increased plasma glucose and insulin levels in diabetic patients as expected. Aspartame ingestion for three days at a dose of 24-48 mg per day and the intake of snacks flavored with 240 mg of aspartame also did not increase fasting plasma glucose levels. These results suggest that acute administration of aspartame has no influence on plasma glucose or insulin levels in diabetic rats and patients with non-insulin-dependent diabetes mellitus.
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PMID:Effects of aspartame on diabetic rats and diabetic patients. 390 28

A 68-year-old male patient without any previous thyroidal disease developed three times of transient primary hypothyroidism associated with protein-calorie malnutrition (PCM). Because of his diabetes mellitus, alcoholic hepatitis, chronic pancreatitis and blind loop syndrome, his nutritional balance was easily disturbed leading to PCM. Although he recurrently developed primary hypothyroidism associated with PCM, this condition was completely restored by protein-calorie repletion. The possibility of dietary iodine deficiency was negated by the observation that his daily urinary iodine secretion was more than 4 mg/day. Plasma amino acid analysis revealed severe depletion of phenylalanine, tyrosine and other essential amino acids and raised the possibility that this hypothyroidism was caused by amino acid deficiency. In order to clarify the mechanisms of this primary hypothyroidism, we have investigated the change of thyroid functions during protein-calorie repletion by total parenteral nutrition (TPN). We then removed iodine from the nutrients for TPN to ascertain that iodine deficiency was not the cause of the primary hypothyroidism in the present case. In spite of the removal of iodine, serum T4 and T3 suddenly increased from 1.1 micrograms/dl and less than 25 ng/dl to 3.5 micrograms/dl and 59 ng/dl, respectively, in a few days after the beginning of TPN. They continued to increase thereafter and reached 6.3 micrograms/dl and 115 ng/dl in 6 weeks. Serum free T4 also showed a sudden increase from 0.56 ng/dl to 1.7 ng/dl after TPN and remained above 1.3 ng/dl thereafter. Serum reverse T3 showed a rapid increase after TPN, but, 4 weeks later, returned to the previous level before TPN. Serum TSH decreased from 120 microU/ml to 17 microU/ml in a few days after TPN and reached a level within normal range in 4 weeks. Serum TBG gradually increased from 10.7 micrograms/ml to 29.2 micrograms/ml in 6 weeks. These results show that the T4 synthesis was extremely impaired by PCM in spite of the strong stimulation by TSH and that this suppression of T4 synthesis by PCM led the patient recurrently to the primary hypothyroidism. We have next investigated the possibility whether the deficiency of phenylalanine and tyrosine could cause a suppression of T4 synthesis because tyrosine is an important substrate of T4. For this purpose we removed phenylalanine and tyrosine from TPN and added iodine to prevent iodine deficiency due to prolonged iodine-depleted nutrition. Reduction of phenylalanine and tyrosine resulted in a marked decrease in serum T4, T3 and TBG in 7 weeks, but gave no change to free T4. Serum TSH remained within normal range.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:[Contribution of amino acid deficiency to primary hypothyroidism associated with protein-calorie malnutrition]. 393 44

Flux through, and maximal activities of, key enzymes of phenylalanine and tyrosine degradation were measured in liver cells prepared from adrenalectomized rats and from streptozotocin-diabetic rats. Adrenalectomy decreased the phenylalanine hydroxylase flux/activity ratio; this was restored by steroid treatment in vivo. Changes in the phosphorylation state of the hydroxylase may mediate these effects; there was no significant change in the maximal activity of the hydroxylase. Tyrosine metabolism was enhanced by adrenalectomy; this was not related to any change in maximal activity of the aminotransferase. Steroid treatment increased the maximal activity of the aminotransferase. Both acute (3 days) and chronic (10 days) diabetes were associated with increased metabolism of phenylalanine; insulin treatment in vivo did not reverse these changes. Although elevated hydroxylase protein concentration was a major factor, changes in the enzyme phosphorylation state may contribute to differences in phenylalanine degradation in the acute and chronic diabetic states. Tyrosine metabolism, increased by diabetes, was partially restored to normal by insulin treatment in vivo. These changes can, to a large extent, be interpreted in terms of changes in the maximal activity of the aminotransferase.
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PMID:The metabolism of L-phenylalanine and L-tyrosine by liver cells isolated from adrenalectomized rats and from streptozotocin-diabetic rats. 400 13

Free amino acid concentrations have been determined in plasma and urine of nonketotic, severely diabetic dogs and age-matched normal controls. Plasma from fasted (as well as fed) diabetics contained supranormal concentrations of several amino acids, including the branched-chain amino acids. In contrast to other species, however, the concentration of only one plasma amino acid (tryptophan) was subnormal in fasted diabetic dogs. Urine collected at the same time showed that the excretion of most amino acids was not abnormal in diabetes. Urinary concentrations of some amino acids were not abnormal despite supranormal levels in plasma. Nevertheless, eight of the 21 amino acids studied reached concentrations significantly greater than normal in the urine of diabetic dogs. Six of the eight amino acids (arginine, histidine, phenylalanine, tyrosine, tryptophan, glutamic acid) showed elevated concentrations in urine even though their plasma concentrations were not elevated. The observed disturbance in the urine/plasma ratio of certain amino acids suggests a possible defect in the renal handling of amino acids in diabetes.
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PMID:Abnormal amino acid concentrations in plasma and urine of experimentally diabetic dogs. 613 39

The cyclic hexapeptide, cyclo (Pro-Phe-D-Trp-Lys-Thr-Phe), I, has been shown to have the biological properties of somatostatin. We now report structure-activity studies which optimize the potency of this cyclic hexapeptide series with the synthesis of cyclo (N-Me-Ala-Tyr-D-Trp-Lys-Val-Phe), II, which is 50-100 times more potent than somatostatin for the inhibition of insulin, glucagon and growth hormone release. The hydroxyl group of tyrosine is seen to lend a 10-fold enhancement to the potency. Potency also is found to be correlated with hydrophobicity. II is found to improve the control of postprandial hyperglycemia in diabetic animals when given in combination with insulin. The analog is found to be quite stable in the blood and in the gastrointestinal tract, but the bioavailability after oral administration is only 1-3%. The biological properties and long duration of II should allow clinical evaluation of the inhibition of glucagon release as an adjunct to insulin in the treatment of patients with diabetes.
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PMID:A super active cyclic hexapeptide analog of somatostatin. 614 33

An alpha-amylase inhibitor isolated from Streptomyces tendae, strain 4158 was re-purified by chromatography on CM- and DEAE-cellulose column. Two inhibitors could be characterized: alpha-amylase inhibitor Hoe-467 A (with aspartic acid as N-terminal residue), and alpha-amylase inhibitor Hoe-467 S (with serine as N-terminal residue). The primary structure was determined by automatic Edman-degradation procedures of the aziranized inhibitor and tryptic peptides, derived from digestions of the performic oxidized, aziranized and maleylated inhibitor, respectively. The alpha-amylase inhibitor Hoe-467 A consists of 74 residues and has a calculated molecular weight of 7958. It is composed of all common amino acids except methionine and phenylalanine. Digestion with pepsin was carried out to determine the disulfide bonds. Two fractions could be isolated, containing one cystine each giving information about the positions of the disulfide bridges. The possible clinical application of the inactivator (diabetes mellitus) is pointed out.
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PMID:[The sequence of the alpha-amylase inhibitor Hoe-467 A (alpha-amylase inactivator Hoe-467 A) from Streptomyces tendae 4158]. 616 65


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