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)

This study reviews clinical studies testing the effects of various doses of aspartame on blood levels of phenylalanine, aspartate, and methanol in normal subjects and known phenylketonuric heterozygotes. The effect of aspartame on the phenylalanine-to-large neutral amino acid ratio under various feeding situations is shown. The clinical studies of aspartame in diabetic subjects are limited to observations of its effects on blood levels of glucose, lipids, insulin, and glucagon. These studies clearly demonstrate the safety of this high-intensity sweetener for use by humans.
Diabetes Care 1989 Jan
PMID:Aspartame metabolism in normal adults, phenylketonuric heterozygotes, and diabetic subjects. 265 51

The human HepG2/erythrocyte glucose-transporter gene, including the promoter region, has been isolated and characterized. The gene, which is approximately 35,000 base pairs, is interrupted by nine intervening sequences or introns. The sequence of the HepG2 glucose-transporter protein predicted from the gene sequence differs from that determined from the published cDNA sequence in having Leu rather than Phe at position 152. In addition, there are several other nucleotide differences between the gene and cDNA sequences in both the coding region and 3'-untranslated region that do not alter the amino acid sequence of the protein. The sequence of the promoter and the site of transcription initiation have also been determined. The promoter region includes a TATA motif and two binding sites for the transcription factor Spl as well as a sequence that is found in the promoter region of several phorbol ester-inducible genes.
Diabetes 1988 May
PMID:Characterization and expression of human HepG2/erythrocyte glucose-transporter gene. 283 52

A coding-length clone of rat liver fructose-1,6-bisphosphatase (EC 3.1.3.11) was isolated by immunological screening of a cDNA library in lambda gt11. Its identity was verified by comparing the deduced amino acid sequence with that obtained by direct sequencing of a complete set of CNBr and proteolytic peptides from the purified protein. The enzyme subunit is composed of 362 amino acids and has N-acetylvaline as the amino-terminal residue. The cDNA, 1255 base pairs (bp) long, consisted of 1086 bp of coding region, 15 bp of 5' untranslated sequence, and 154 bp at the 3' untranslated end. The 3' untranslated sequence contained a polyadenylylation signal (AATAAA) followed after 30 bp by a stretch of 7 adenines at the end of the clone. The deduced amino acid sequence was identical to the primary sequence of the protein and confirmed the alignment of five nonoverlapping peptides. It also confirmed the 27-residue extension, unique to the rat liver subunit, ending with a carboxyl-terminal phenylalanine. RNA blot analyses using the radiolabeled liver cDNA as a probe revealed a single band of fructose-1,6-bisphosphatase mRNA, 1.4 kilobases long, in liver and kidney but not in nongluconeogenic tissues. Fructose-1,6-bisphosphatase mRNA was increased 10-fold in livers from diabetic rats and was reduced to control levels after 24 hr of insulin treatment, suggesting that the changes in enzyme activity observed in diabetes and after insulin treatment are due to alterations in mRNA abundance.
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PMID:cDNA sequence of rat liver fructose-1,6-bisphosphatase and evidence for down-regulation of its mRNA by insulin. 284 61

The mechanisms of hypoglycaemic action of a 'second-generation' sulphonylurea, gliclazide, and a synthetic human growth hormone fragment, hGH 6-13 (Leu-Ser-Arg-Leu-Phe-Asp-Asn-Ala), were compared at the cellular level in rats. Both compounds were shown to be hypoglycaemic in vivo although their molecular structures were totally different. Gliclazide was markedly insulinotropic, as are all hypoglycaemic sulphonylureas, whereas hGH 6-13 had no visible effect on basal levels of plasma insulin. However, in vitro studies with isolated pancreatic islets revealed that hGH 6-13 significantly augmented insulin secretion in the presence of exogenous glucose. One other major difference was that gliclazide had no direct effect on insulin receptor function while the synthetic hGH 6-13 increased the binding of insulin to specific receptors on isolated cells. Results suggested that the human growth hormone fragment hGH 6-13 could be a potential anti-diabetes drug with the ability to potentiate circulating insulin action and to achieve blood glucose normalisation.
Diabetes Res Clin Pract 1988 May 19
PMID:A comparison of cellular actions between gliclazide and a hypoglycaemic peptide fragment of human growth hormone (hGH 6-13). 304 43

The pancreatic effect of a hypoglycaemic fragment of human growth hormone containing the amino acid sequence Leu-Ser-Arg-Leu-Phe-Asp-Asn-Ala (hGH 6-13), was investigated. In partially pancreatectomized rats, hGH 6-13 (3 mg/kg body weight) enhanced glucose utilization in blood as demonstrated in intravenous glucose tolerance tests (IVGTTs). However, the basal levels of plasma insulin in the animals were apparently not affected by acute administration of the hGH fragment and only slightly modulated with prolonged hGH fragment treatment. Direct studies with the isolated pancreatic islets from normal and hGH 6-13 treated rats showed that hGH 6-13 did not influence in vitro or ex vivo insulin release in the absence of glucose but significantly potentiated the glucose-induced insulin secretion of the pancreatic islets from treated animals. An increase of 42% in glucose oxidation of the isolated pancreatic islets after exposure to hGH 6-13 was observed. This study reveals significant differences in the molecular mechanism of the hypoglycaemic action between the hGH fragments and orally active sulphonylureas. The findings suggest that the hypoglycaemic hGH fragments, structurally unrelated to sulphonylureas, could be a new group of effective agents to achieve blood glucose normalization without the risk of hyperinsulinaemia, as their pancreatic effect is glucose-dependent.
Diabetes Res 1988 Mar
PMID:Pancreatic effect of a hypoglycaemic fragment of human growth hormone (hGH 6-13). 304 17

A man with diabetes mellitus, chronic hepatitis, chronic pancreatitis, and blind loop syndrome but without any previous thyroid disease developed three episodes of transient primary hypothyroidism associated with protein-calorie malnutrition (PCM). Clinical examinations suggested that this primary hypothyroidism was not caused by chronic thyroiditis, iodine deficiency, or iodine excess. Since the three times association of primary hypothyroidism with PCM suggested the possibility that the primary hypothyroidism was caused by PCM, we have tried to clarify its mechanism. For this purpose we have investigated the change of thyroid functions during protein-calorie repletion and the effect of amino acid deficiency. Total parenteral nutrition with full supplementation of amino acids resulted in a rapid increase in serum thyroxine (T4), triiodothyronine (T3), free T4, and reverse T3, and subsequently, a rapid decrease in TSH in several days after the nutrition was begun. When amino acid solution was changed to that depleted of phenylalanine and tyrosine after the restoration of thyroid functions, serum T4 and T3 showed a gradual decrease, but serum free T4 and TSH remained within normal range. However, resupplementation of phenylalanine and tyrosine after 8 weeks of depletion gave a rapid increase in serum T4, T3, free T4, and reverse T3. These results suggested that the primary hypothyroidism was caused by an impaired T4 production and that the deficiency of amino acids in PCM partly contributed to the impairment of T4 production.
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PMID:Primary hypothyroidism in an adult patient with protein-calorie malnutrition: a study of its mechanism and the effect of amino acid deficiency. 312 81

Aromatic amino acids tyrosine and phenylalanine have been measured on paper with dried blood samples, using high performance liquid chromatography (HPLC) in reverse phase. The aim of this procedure is to discriminate unclear cases of general screening for aminoacidopathies avoiding unnecessary retest. Plasma normal values of tyrosine and phenylalanine have been obtained in full term babies (0.82 +/- 0.39 mg/dl and 0.53 +/- 0.23 mg/dl) preschool boy (0.78 +/- 0.21 mg/dl and 0.63 +/- 0.20 mg/dl), school boys (0.89 +/- 0.16 and 0.76 +/- 0.22 mg/dl) and normal adults (1.48 +/- 0.19 and 1.41 +/- 0.12 mg/dl). In order to assess if fasting levels can be altered by breast feeding or formula feeding, a sample was obtained after various feeds and postprandially. Results show no differences before or after feeding. A group of malnourished infants showed greater plasma values of tyrosine and phenylalanine (p less than 0.002) conversely a group children suffering for diabetes showed no differences when comparing with matched age controls. In conclusion, measurement of tyrosine and phenylalanine on dried blood in filter paper is accurate enough, to avoid unnecessary recall in unclear cases of screening, and those levels do not alter significantly with normal milk intake.
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PMID:[Reference levels for phenylalanine and tyrosine in discs impregnated with blood during analysis by HPLC]. 317 55

We examined neutrophil adherence to bovine aortic endothelial cells in 26 patients with diabetes compared with age- and sex-matched controls. The adherence of chromium 51-labeled neutrophils from patients with diabetes in the basal state and after incubation with phorbol myristate acetate (PMA) but not N-formyl-methionyl-leucyl-phenylalanine (FMLP) was decreased significantly. A subset of 16 of 26 patients demonstrated highly significant decreases in basal adhesion. No significant correlation was found between defective adherence and metabolic control as assessed by plasma glucose level (range 44 to 508 mg/dl) and hemoglobin A1 level (range 7.7% to 17.1%) at the time of study. Plasma from patients with diabetes increased adherence of both diabetic and control neutrophils in the basal state. The adherence-augmenting factor in diabetic plasma was found to be nonfilterable and partially heat labile and to manifest the characteristics of a protein. The adhesive effects of diabetic plasma were mediated through alterations in endothelium rather than neutrophils. Diabetic neutrophil aggregation induced by PMA, FMLP, and calcium ionophore was normal in all patients examined, regardless of the aggregating agent used. Fibronectin release in the basal state and after stimulation with FMLP was found to be comparable in diabetic and control neutrophils. These studies demonstrated intrinsic adhesive dysfunction of diabetic neutrophils and a factor or factors in diabetic plasma that enhanced adherence to endothelium. These cellular and humoral factors may act together to prevent tissue emigration of neutrophils and may contribute to the pathogenesis and susceptibility of infection in diabetes.
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PMID:Neutrophil adhesive dysfunction in diabetes mellitus; the role of cellular and plasma factors. 334 42

A simple and reliable method is described which is suitable for estimation of a whole blood phenylalanine concentration for the patient with PKU in various settings including the physician's office and the home. Excellent correlations were obtained between this method and weighed phenylalanine standards, as well as with measurement of phenylalanine in serum, plasma, and whole blood, using the McCaman-Robins fluorometric assay. Increasing the frequency and rapidity of feedback to the patient should improve metabolic control, just as home glucose monitoring has for the patient with diabetes mellitus. This method is immediately adaptable to monitoring patients with tyrosinemia, and with substitution of the appropriate amino acid ammonia lyase could be used for other amino acidemias.
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PMID:Blood phenylalanine estimation for the patient with phenylketonuria using a portable device. 335 20

The effects of fasting, refeeding, and streptozotocin-induced experimental diabetes on free amino acid concentrations in the rat exocrine pancreas were investigated. Extracts of pancreatic tissue and plasma were analyzed using high-performance liquid chromatography (HPLC). Pancreatic and plasma concentrations of alanine were reduced in animals fasted for 24 to 72 h. Pancreatic concentrations of leucine, arginine, and glutamine were increased after fasting for 48 h, and concentrations of all essential amino acids plus the nonessential amino acids glycine, serine, taurine, and glutamine were elevated after fasting for 72 h. Refeeding 72 h fasted animals for 3 h or 24 h had a negligible effect on the plasma amino acid concentrations, but markedly lowered the concentration of essential amino acids within the pancreatic tissue. Diabetes lowered the total plasma amino acid concentration from 4.9 mM to 3.1 mM but increased the total pancreatic tissue amino acid level from 16.4 mM to 18.3 mM. Efflux of intracellular amino acids into the circulation of the isolated perfused pancreas was assessed under basal conditions and in response to a vascular amino acid challenge using HPLC. L-serine transstimulated efflux of a large number of amino acids, whereas cellular efflux was only minimally affected by L-phenylalanine. Fasting and diabetes-induced increases in essential amino acid concentrations within the pancreas may reflect decreased protein synthesis, accelerated protein catabolism, or a change in membrane transport. Altered intracellular amino acid levels may directly regulate exchange diffusion of intracellular for extracellular amino acid(s).
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PMID:Fasting, refeeding and diabetes modulate free amino acid concentrations in the rat exocrine pancreas: role of transstimulation in amino acid efflux. 336 44


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