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Biomedical subjects

T M Smith

Publications and source records attributed to T M Smith.

At least 109 records · Page 6Linked to original sources

Inhibition of key glycolytic enzymes from rabbit kidney medulla by free fatty acids in vitro.

In vitro incubation of key glycolytic enzymes in supernatant fluids from rabbit kidney medulla with increasing concentrations of sodium laurate resulted in progressive inhibition of hexokinase, phosphofructokinase and pyruvate kinase. A corresponding reduction in the production of lactate from glucose was also observed. The possible effects of these enzyme inhibitions on the naturesis observed during fasting are discussed.

Animals↗

Deranged insulin-secretory dynamics in offspring of two diabetic parents after double stimulation with intravenous glucose.

Nine offspring of two diabetic parents and 18 normals were studied with two intravenous glucose loads (o.5 gm./kg. body weight), 60 minutes apart. By thus stressing the beta cell, subtle defects could be identified in the prediabetics: (1) An inverse relationship between insulin peak response and insulin concentration 60 minutes postglucose was seen, a phenomenon exactly the opposite to that seen in normals. (2) Insulin peak response was delayed slightly after the first pulse and significantly after the second. (3) A less effective handling of the glucose load when compared with normals was brought out by the second stimulation. (4) There was a significant reduction in the insulin response per unit change in glucose after the first glucose pulse that was accentuated after the second pulse. This double-stimulation technique amplifies previously detected slight but significant defects in insulin secretion that might help to identify a diabetes-prone population.

Adolescent↗

Monozygotic triplets with discordance for diabetes mellitus and diabetic microangiopathy.

A set of monozygotic triplets (PE.K., P.K., S.K.) has been studied. There is no diabetes in first-degree relatives. PE.K. developed insulin-requiring (60 U. NPH) diabetes at the age of 13 years. Over a period of 11 years since that time, numerous studies of insulin and growth-hormone secretion were performed on P.K. and S.K., including multiple oral glucose tolerance tests (OGTTs), cortisone-primed oral glucose tolerance tests (C-OGTTs), intravenous glucose tolerance tests (IVGTTs), and intravenous tolbutamide tests (IVTTs). The results of each test were compared with age- and sex-matched control subjects. P. K. developed insulin-requiring (56 U. NPH) diabetes after remaining discordant for eight years. Glucose, insilin, and growth-hormone responses during all tests were normal except during the IVGTT performed four months prior to the onset of diabetes. This last IVGTT revealed a glucose disappearance rate of 0.98 per cent per minute, and the slope of the regression line of serum-insulin response (IRI) on blood glucose (BG) was markedly decreased to 0.005 micronU./ml. IRI/mg./dl. BG (controls 0.340 +/- 0.04; mean +/- S.E.M.). The insulin responses in P.K. and S.K. were similar during all OGTTs, C-OGTTs, and IVTTs. S.K. has continued to maintain normal glucose tolerance and normal insulin and growth-hormone responses during all tests. The histocompability antigen studies have revealed HLA-A2, AW24, BW15, and BW40 phenotype in these monozygotic triplets. Muscle capillary basement membranes of the nondiabetic triplet were normal, whereas both diabetic triplets manifested evidence of capillary basement membrane thickening. The clinical and biochemical profiles in these triplets and the capillary basement membrane data lend strong credence to the role of "nongenetic" determinants in the development of "genetic" diabetes as well as diabetic microangiopathy in juvenile-onset-type diabetes.

Adolescent↗

Decarboxylation of newly formed DOPA by caudate nucleus synaptosomal particles.

The present study compares dopamine formation from two different sources of DOPA: preformed and added to the medium and that newly formed by the hydroxylations of phenylalanine or tyrosine. Synaptosomal preparations from rat brain caudate nucleus were incubated with 3H-labeled DOPA mixed as cosubstrate with either [14C]phenylalanine or [14C]tyrosine. Following the incubation, DOPA and dopamine were separated and their isotope ratios (isotope in phenylalanine (tyrosine) X 100/isotope in DOPA cosubstrate) were determined and compared. The results show that the ratio in dopamine was not only different from that in DOPA but was in fact 8.3-15.0 times higher. Although the absolute values of the isotope ratios were affected by any changes of the cosubstrate concentrations, the ratio in dopamine was found to be higher than in DOPA at all the substrate concentrations tested. When the synaptosomes were separated post-incubation from the medium and analyzed, the ratio in dopamine was also found to be higher than that in DOPA. Also, the large difference between the intrasynaptosomal ratios persisted throughout the incubation period ranging from 10 to 45 min. The results suggest that the DOPA which is newly formed by the hydroxylations, (a) may not be freely exchangeable with added DOPA because of compartmentation and (b) may be preferentially decarboxylated to dopamine.

Animals↗

Two-column gas-liquid chromatography of fatty acid methyl esters.

Fatty acid methyl esters were separated into fractions according to chain length on a nonpolar gas-liquid chromatographic column. These fractions were collected and rechromatographed on a polar column. Temperature programming was used in both cases. Data are given for the accuracy of the double procedure applied to a synthetic mixture.

Fatty Acids↗