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Biomedical subjects

K H Gabbay

Publications and source records attributed to K H Gabbay.

At least 91 records · Page 5Linked to original sources
PubMed1976

The biosynthesis of human hemoglobin A1c. Slow glycosylation of hemoglobin in vivo.

Hemoglobin A1c, the most abundant minor hemoglobin component in human erythrocytes, is formed by the condensation of glucose with the N-terminal amino groups of the beta-chains of Hb A. The biosynthesis of this glycosylated hemoglobin was studied in vitro by incubating suspensions of reticulocytes and bone marrow cells with [3H]leucine or 59Fe-bound transferrin. In all experiments, the specific activity of Hb A1c was significantly lower than that of Hb A, suggesting that the formation of Hb A1c is a posttranslational modification. The formation of Hb A1c in vivo was determined in two individuals who were given an infusion of 59Fe-labeled transferrin. As expected, the specific activity of Hb A rose promptly to a maximum during the 1st week and remained nearly constant thereafter. In contrast, the specific activity of Hb A1c and also of Hbs A1a and A1b rose slowly, reaching that of Hb A by about day 60. These results indicate that Hb A1c is slowly formed during the 120-day life-span of the erythrocyte, probably by a nonenzymatic process. Patients with shortened erythrocyte life-span due to hemolysis had markedly decreased levels of Hb A1c.

Anemia, Hemolytic↗
PubMed1975

Vesicular binesis: glucose effect on insulin secretory vesicles.

Binesis is a process whereby the membrane of the insuline secretory vesicle in the beta cell forms a lingula that indents the vesicular membrane of an adjoining secretory vesicle of the plasma membrane. Vesicular binesis in beta cells increases when islets of Langerhans are incubated at a stimulatory glucose concentration (300 miligrams per 100 milliliters). These vesicular membrane alterations may be the morphological concomitants of activation of the insulin secretory vesicle, and indicate an active role for the vesicle and its membrane in the release mechanism.

Animals↗
PubMed1975

Hyperglycemia, polyol metabolism, and complications of diabetes mellitus.

This brief review of the sorbitol pathway has attempted to present our current knowledge of this accessory pathway of glucose metabolism in the development of some diabetic complications. Clearly hyperglycemia in the diabetic patient is an important factor controlling the activity of the sorbitol pathway. Hyperglycemia in both diabetic patients and experimental animals results in significant accumulations of the products of this pathway in some tissues, and these diabetic manifestations. The development of inhibitors of the aldose reductase enzyme affords new means for preventing and treating some of these complications. Nevertheless, we are still hampered by the lack of knowledge of the normal role of this pathway in tissue metabolism. Many technical problems still exist concerning sensitive and specific assays for the products of the sorbitol pathway in tissue studies, as well as with valid techniques for the measuremtn of the activity of this pathway in clinical situations. It is hoped that clinical studies with aldose reductase inhibitors in the future will further clarify the importance of this accesory pathway of glucose metabolism in diabetes.

Animals↗
PubMed1973

Polyol accumulation in galactosemic and diabetic rats: control by an aldose reductase inhibitor.

An orally active inhibitor of aldose reductase, 1,3-dioxo-1H-benz[de]-isoquinoline-2(3H)acetic acid (AY-22,284), prevented cataractous changes in cultured lenses exposed to high concentrations of galactose. When given orally, AY-22,284 markedly decreased the accumulation of polyols in the lenses and sciatic nerves of galactosemic rats and rats with streptozotocin-induced diabetes. In addition, treatment of galactosemic rats with AY-22,284 effectively suppressed the formation of cataracts.

Acetates↗
PubMed1972

Pancreatic beta-cell web: its possible role in insulin secretion.

A cortical band of fine microfilaments is consistently observed in the beta cells of the rat pancreas. Alteration of this cell web by cytochalasin B is associated with an enhancement of glucose-induced secretion of insulin by isolated islets. The microfilamentous web of the beta cell may play an important role in the emiocytosis of insulin secretory granules, by controlling their access to the cell membrane.

Animals↗
PubMed1972

Inhibition of glucose-induced release of insulin by aldose reductase inhibitors.

ALDOSE REDUCTASE (ALDITOL: NADP oxidoreductase, EC 1.1.1.21) is the enzyme responsible for the conversion of glucose to its sugar alcohol, sorbitol. In this study, aldose reductase and a closely related enzyme, L-hexonate dehydrogenase (L-gulonate: NADP oxidoreductase, EC 1.1.1.19), were purified from rat pancreas. Glutaric acid, 2,4-dimethyl glutaric acid, 3,3-tetramethylene glutaric acid, and colchicine inhibited both enzymes, albeit with different potencies. These compounds also inhibited both phases of glucose-induced release of insulin by the perfused rat pancreas. The potencies of these inhibitors in depressing the release of insulin correlated with their effectiveness in inhibiting aldose reductase. At higher concentrations of inhibitors, tolbutamide-induced release of insulin was also depressed. The addition of exogenous sorbitol to pancreases treated with glutaric acid restored their ability to respond to glucose and tolbutamide. These findings suggest that the conversion of free intracellular glucose to sorbitol in the beta cell is an essential step in the glucose-induced release mechanism.

Alcohol Oxidoreductases↗
PubMed1972

Histamine release from human leukocytes: modulation by a cytochalasin B-sensitive barrier.

Cytochalasin B, a metabolic product of several fungi, enhances up to 10-fold the sensitivity and reactivity of human leukocytes to antigen E or anti-IgE-mediated histamine release. The effect of cytochalasin B is a result of its action on the second, antigen-independent, stage of histamine release. These data suggest that normally, antigen-triggered histamine release is modulated by a cytochalasin-sensitive barrier (CSB). This CSB modulation of histamine release can be separated from the modulating effect of cyclic adenosine monophosphate (AMP).

Antigens↗
PubMedDate not supplied

Sequence of cDNA encoding human insulin-like growth factor I precursor.

Somatomedins (SM) or insulin-like growth factors (IGF) constitute a heterogeneous group of peptides with important growth-promoting effects in vitro as well as in vivo. Amino acid sequences have been determined for only two of them, IGF-I and IGF-II, which are highly homologous. IGF-I, which is identical with SM-C, is composed of 70 amino acid residues and IGF-II contains 73 amino acids and may be identical with SM-A. Other peptides with different charge properties but with similar SM-like or insulin-like behaviour in biological and receptor assays, have been described but have not yet been fully characterized. The liver is known to be a major site of production of these peptides, but many other tissues--especially in the fetus--may synthesize them as well. We report here the nucleotide sequence of a human liver cDNA encoding the complete amino acid sequence of IGF-I. The IGF-I coding region is flanked by sequences encoding an amino-terminal peptide of at least 25 amino acid residues and a carboxyl-terminal peptide of 35 amino acids. This provides evidence that IGF-I is synthesized as a precursor protein and that formation of IGF-I from this precursor requires proteolytic processing at both ends.

Base Sequence↗