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

The effect of diabetes (streptozotocin, 65 mg/kg ip), dietary protein intake (15-60%), and plasma amino acid concentrations on brain large neutral amino acid levels in rats was examined. After 20 days, the plasma concentrations of methionine and the branched chain amino acids (BCAA), valine, isoleucine, and leucine were increased in diabetic rats. In brain tissue, methionine and valine levels were increased but threonine, tyrosine, and tryptophan concentrations were depressed. Increased protein consumption promoted a diabetic-like plasma amino acid pattern in normal rats while enhancing that of diabetic animals. However, with the exception of threonine, glycine, valine, and tyrosine, there was little effect on brain amino acid levels. A good association was found between the calculated brain influx rate and the actual brain concentration of threonine, methionine, tyrosine, and tryptophan in diabetic animals. There was no correlation, however, between brain influx rate and brain BCAA levels. Thus, the brain amino acid pattern in diabetes represents the combined effects of insulin insufficiency and composition of the diet ingested on plasma amino acid levels as well as metabolic adaptation within the brain itself.
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PMID:The effect of insulin deficiency, dietary protein intake, and plasma amino acid concentrations on brain amino acid levels in rats. 404 90

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

1. Concentrations of polyamines, amino acids, glycogen, nucleic acids and protein, and activities of ornithine decarboxylase and S-adenosylmethionine decarboxylase, were measured in livers from control, streptozotocin-diabetic and insulin-treated diabetic rats. 2. Total DNA per liver and protein per mg of DNA were unaffected by diabetes, whereas RNA per mg of DNA and glycogen per g of liver were decreased. Insulin treatment of diabetic rats induced both hypertrophy and hyperplasia, as indicated by an increase in all four of these constituents to or above control values. 3. Spermidine content was increased in the livers of diabetic rats, despite the decrease in RNA, but it was further increased by insulin treatment. Spermine content was decreased by diabetes, but was unchanged by insulin treatment. Thus the ratio spermidine/spermine in the adult diabetic rat was more typical of that seen in younger rats, whereas insulin treatment resulted in a ratio similar to that seen in rapidly growing tissues. 4. Ornithine decarboxylase activity was variable in the diabetic rat, showing a positive correlation with endogenous ornithine concentrations. This correlation was not seen in control or insulin-treated rats. Insulin caused a significant increase in ornithine decarboxylase activity relative to control or diabetic rats. 5. S-Adenosylmethionine decarboxylase activity was increased approx. 2-fold by diabetes and was not further affected by insulin. 6. Hepatic concentrations of the glucogenic amino acids, alanine, glutamine and glycine were decreased by diabetes. Their concentrations and that of glutamate were increased by injection of insulin. Concentrations of ornithine, proline, leucine, isoleucine and valine were increased in livers of diabetic rats and were decreased by insulin. Diabetes caused a decrease in hepatic concentration of serine, threonine, lysine and histidine. Insulin had no effect on serine, lysine and histidine, but caused a further fall in the concentration of threonine.
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PMID:Polyamine and amino acid content, and activity of polyamine-synthesizing decarboxylases, in liver of streptozotocin-induced diabetic and insulin-treated diabetic rats. 616 56

Experimental diabetes was induced in the bovine in two experiments by intravenous injection of alloxan (110 mg/kg or 60 mg/kg) in order to determine the role of insulin on nitrogen and amino acid metabolism. In experiment 1, insulin was injected to control hyperglycemia in one group of steers immediately after alloxan treatment (110 mg/kg). In experiment 2, insulin was injected beginning 6 days following alloxan treatment (60 mg/kg) to control hyperglycemia. Plasma glucose increased to 800-1400 mg/100 ml within 5-6 days following alloxan administration (experiment 1). A large surge of insulin release occurred immediately after alloxan administration, which was followed by a decrease in insulin concentrations to subnormal levels in those animals not treated with insulin. Alloxan-treated steers became acidotic by day 2 as indicated by a drop in blood pH, bicarbonate and base excess. Acid-base status improved in steers treated with alloxan plus insulin but did not return to normal. Alloxan treatment caused a marked increase in serum urea-N and creatinine concentrations and insulin treatment of the alloxanized animal decreased both serum urea-N and creatinine concentrations. Treatment with alloxan caused a two- to threefold increase in the plasma concentrations of valine, isoleucine, leucine, lysine and 3-methylhistidine and a decrease in alanine, threonine, citrulline and arginine. Insulin treatment of the alloxanized bovine maintained normal plasma concentrations of valine, isoleucine and leucine. In a third experiment, the injection of insulin (6 U/kg) into normal cattle caused a transient decline in plasma concentrations of branched-chain amino acids (BCAA); however, if glucose was continuously infused (125 mmol/hour) in addition to insulin injection, a sustained decrease in plasma BCAA concentrations was observed. These data support the concept that insulin promotes decreased plasma concentrations of BCAA either by promoting tissue anabolism by stimulating tissue uptake and protein synthesis or decreasing proteolysis and BCAA release.
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PMID:Role of insulin in regulating amino acid metabolism in normal and alloxan-diabetic cattle. 634 16

Semisynthetic human insulin is prepared from porcine pancreas by chemical methods involving the substitution of porcine B-30 alanine with threonine. To compare the effectiveness of porcine and semisynthetic human insulins, eight insulin-dependent diabetic patients were evaluated during two separate periods using a glucose-controlled insulin infusion system. During each 36-h period, patients received either porcine or semisynthetic human insulin. Patients ingested mixed meals. The mean daily insulin requirements for porcine and semisynthetic human insulins were 84 +/- 9 U and 85 +/- 6 U (+/- SEM), respectively (P = NS). Mean blood glucose values were similar at 95 +/- 1 mg/dl for porcine and 101 +/- 3 mg/dl with semisynthetic human insulin (P = NS). Prior metabolic control or insulin antibody levels did not correlate with intravenous insulin requirements. These studies indicate that semisynthetic human insulin is as effective as porcine insulin in maintaining near-normal blood glucose control in short-term intravenous studies using artificial pancreas techniques in insulin-dependent diabetes.
Diabetes Care
PMID:Comparison of the biologic activity of porcine and semisynthetic human insulins using the glucose-controlled insulin infusion system in insulin-dependent diabetes. 634 25

Isolates of Fusobacterium that differ from type strains of various fusobacterial species with respect to DNA sequence, cellular fatty acid composition, and biochemical activity, were obtained from periodontitis lesions in a patient with insulin-dependent diabetes mellitus. These isolates have the following distinguishing characteristics: 28% guanine + cytosine content; 40% or less DNA homology with type strains of representative fusobacterial species; cell size, 0.5 - 1 X 4 -100 microns; absence of motility; ability to ferment glucose, fructose, and galactose, but not 25 other carbohydrates; ability to produce indole; ability to hydrolyze hippurate but not esculin; sensitivity to bile; ability to produce little or no gas; ability to utilize threonine but not lactate. We propose that the organisms be classified as a distinct species of Fusobacterium to be named Fusobacterium periodonticum. The type strain of this new species has been deposited with the American Type Culture Collection under the designation ATCC 33693.
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PMID:Fusobacterium periodonticum, a new species from the human oral cavity. 657 99

Blood-borne free amino acids of 100 mothers were tested immediately after birth. Fifty of the probands had diabetes, while the other 50 were metabolically intact. Amino acid imbalance was recorded by means of multidimensional variance analysis from the diabetics and found to have been largely associated with glutamic acid threonine, alanine, glycine-serine, and glutamine.--A formula, derived from the aforementioned relevant amino acid concentrations, is given in this paper together with a nomogram (which might be used instead of the formula) for determination of diabetes-caused alterations in the amino acid spectrum
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PMID:[Amino acid imbalances in blood of pregnant women with diabetes and in blood of their newborns--limit values for screening (author's transl)]. 681 May 83

Biosynthetic human insulin (BHI) produced by recombinant DNA technology has been proven to be identical to pancreatic human insulin. It differs from pork insulin in one carboxy-terminal amino acid of the B-chain, where alanine substitutes for threonine. This leads to a higher hydrophilicity and usually lowers the tendency of insulin molecules to aggregate. To study its biologic effect in man, the Gerritzen test was applied. BHI regular (10 IU) or purified pork insulin (PPI) (10 IU) was injected subcutaneously to evaluate the insulin action profile. The time course of plasma glucose levels under both BHI and PPI did not significantly. BHI seems to lower the blood glucose somewhat faster during the first 30 min and, during the late phase, somewhat less than pork insulin. In general, for both BHI and PPI, the onset of action occurs within 15 and 30 min; after 60 min, plasma glucose levels drop by 44.3% for BHI and by 40% for PPI. The plasma glucose minimum was reached about 2 h after injection; therefore, the slope of the plasma glucose fall after 60 min was only marginal. The minimum levels were steady over about 1.75 h. At 2.5 h postinjection plasma glucose rose gradually and reached starting levels after about 7 h. BHI was as well tolerated in the intradermal skin testing as were pork insulin and a placebo solution.
Diabetes Care
PMID:Comparison of biosynthetic human insulin and pork insulin in the Gerritzen test. 701 22

Insulin analogues with different amino acids, including threonine, alanine, L-leucine, D-leucine, L-leucine amide, phenylalanine, tri-alanine, or desalanine, at the B-30 position were semisynthesized from pork insulin by the new enzymatic method. The order of ability of the insulin analogues to bind to anti-insulin sera was [AlaB-30] greater than desalanine greater than [ThrB-30] greater than [Ala-Ala-AlaB-30] greater than [D-LeuB-30], [Leu-NH2B-30],[PheB-30] greater than desoctapeptide greater than or equal to [LeuB-30]. The ability of insulin analogues with different amino acids at B-30 to bind to receptors, as well as their biologic potency tested with glucose uptake in isolated rat adipocytes, was comparable among the analogues. These results suggest that [LeuB-30]-insulin demonstrated the least immunoreactivity and has full activity in receptor binding and biologic effect, and that it may be useful for treatment of anti-insulin antibody-mediated insulin resistance.
Diabetes 1981 Jun
PMID:Immunoreactivity and biologic activity of semisynthetic [LeuB-30]-insulin: potential value in the treatment of insulin antibody-mediated insulin resistance. 701 15

Free amino acids were studied in the blood of 50 newborns each of women with intact metabolism and of diabetic mothers. The tests were conducted immediately after delivery and on the fifth day of age. Amino acid imbalance reflected, after birth, in changed concentrations of glutamic acid-threonine, alanine and glycin-serine was recordable from newborns of the diabetic mothers. However, nothing but significant changes in concentrations of glutamic acid-threonine and alanine was recordable on the fifth day of age. --An account is given of the formulae and nomograms (applicable instead of these formulae) for postpartum amino acid concentrations and for concentrations on the fifth day of age, being established by discriminant analysis. These can be used to identify alterations inflicted upon amino acid metabolism by diabetes mellitus.
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PMID:[Amino acid imbalance in the blood of pregnant diabetic women and their newborn infants--limit values for screening. II. Neonatal amino acid imbalance]. 718 Feb 43


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