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Lipodystrophic muscularhypertrophy (lipoatrophic diabetes)
Volume 65
Number 6 Part 2
demonstrate that (1) earlier and increased death rates were observed in splenectomized mice infected with small numbers of D. pneumoniae type 6, (2) diminished resistance persisted for a prolonged period of time after splenectomy, and (3) increased susceptibility could not be related to a deficiency in blood clearance of pneumocoeci.
METABOLISM
60. Lipodystrophic muscular hypertrophy (lipoatrophic diabetes) N. Mosely, ~ M. D. Bogdonoff, ~ N. Kirshner, ~ R. S. Stempfel, Jr., and J. B. Sidbury, Jr., Duke University Medical
Center, Durham, N. C. The syndrome consisting of absence of subcutaneous fat, hyperlipemia, hepatomegaly, and statural overgrowth is followed in later years by ketosis-resistant diabetes mellitus. A 3~2-year-old girl with this syndrome has been studied in an attempt to delineate the mechanisms involved in the condition. Intravenous radiopalmitate was found to be incorporated into serum triglycerldes in increased amounts when she was lipemic. Epinephrine administration did not result in a rise in serum free fatty acids (FFA). The serum FFA level fell with exogenous insulin but not with tolbutamide, whereas the glucose response was similar. The response to intravenous heparin indicated a normal serum lipoprotein lipase. Intravenous labeled norepinephrine revealed a marked increase in normetanephrine excretion. Leukocyte triglyceride formation and phospholipid incorporation from labeled palmitate, tripalmitin, BOH, and glucose were normal. In contrast to the normal, insulin inhibited palmltate and B O H oxidation by white blood cells. Ketosteroid excretion was intermittently elevated. Assay of serum insulin and growth hormone levels is in progress. The results are informative: of tile role of adipose tissue in fatty acid metabolism and the role of the liver in hyperlipemia. Abnormalities of epinephrine metabolism should be investigated in other cases of hyperlipemia. The possibility of an abnormal insulin with altered pituitary feedback is suggested.
61. Studies of active transport of calcium, magnesium, and sulfate by the small intestine Constantine Anast, Robin Kennedy, ~ George Volk, "~ and Lueile Adamson, ~ Department of Pediatrics, University of Missouri School of Medicine, Columbia, Mo. Observations were made of the active transport of calcium, magnesium, and sulfate in the small intestine of the rabbit utilizing the everted
Abstracts
1 10 5
gut-sac technique of Wilson and Weisman. The most active transport of sulfate occurred in the distal third of the small intestine. Sulfate was not found to be actively transported in the proximal small gut and relatively little transport occurred in the midgut. Dinitrophenol ( D N P ) , anaerobiosis, and ouabain (10 -5 M) all inhibited active transport of sulfate. Active transport was almost completely inhibited when lithium chloride, potassium chloride, rubidium chloride, cesium chloride, choline chloride, or Tris buffer was substituted for sodium chloride in equimolar concentrations (120 mM.) in the standard buffer medium. In contrast to sulfate, calcium was found to be actively transported only in the proximal small gut. Anaerobiosis, DNP, and ouabain (I0 -s M but not 10 -2 M) inhibited active transport. Inhibition resulting when LiC1, NH~C1, KC1, RbC1, or CsC1 was substituted for NaC1 in the standard buffer medium appeared to be related to the atomic weight of the cation; the smaller the atomic weight, the greater the inhibition. Of the five inorganic univalent cations studied, only cesium with the greatest atomic weight failed to inhibit the active transport of calcium. Transport of calcium increased progressively as sodium was increased and lithium decreased, with the sum of sodium and lithium held constant at 120 raM. Magnesium, unlike calcium and sulfate, was not actively transported by any segment of the small intestine. Neither was active transport of magnesium observed in intestinal segments from magnesium-deficient animals.
62. Multiple amino acid carrier systems in plasma membranes: Genetic implications Charles R. Striver and Onslow H. Wilson, ~" McGill University and Montreal
Children's Hospital, Montreal, Quebec From evidence from heritable diseases and infusion experiments in mammals, amino acid transport mechanisms can be divided into four groups: (1) cyclic and neutral aliphatic amino acids, except group 2; (2) imino acids and glycine; (3) "dibasics" and cystine; (4) dicarboxylics. The "'common" transport mechanisms of the second and third groups were studied in detail. Male hooded rats were infused with individual amino acids of both groups; only intragroup competition for renal absorption occurred. In vitro studies measuring uptake of labeled amino acids into rat kidney cortex slices were then performed and transport kinetics (Michaelis-Menten) were analyzed. T h e K m and Ki values for each amino acid were used to describe its relation to the sites at which it acted as substrate and as competitive inhibitor. In addition to the division into two major groups, an individual transport site, with its own specificity characteristics, was found for each amino acid in the two groups. Therefore a single mutation affecting group transport (e.g., cystinuria) would affect multiple
Number 6 Part 2
demonstrate that (1) earlier and increased death rates were observed in splenectomized mice infected with small numbers of D. pneumoniae type 6, (2) diminished resistance persisted for a prolonged period of time after splenectomy, and (3) increased susceptibility could not be related to a deficiency in blood clearance of pneumocoeci.
METABOLISM
60. Lipodystrophic muscular hypertrophy (lipoatrophic diabetes) N. Mosely, ~ M. D. Bogdonoff, ~ N. Kirshner, ~ R. S. Stempfel, Jr., and J. B. Sidbury, Jr., Duke University Medical
Center, Durham, N. C. The syndrome consisting of absence of subcutaneous fat, hyperlipemia, hepatomegaly, and statural overgrowth is followed in later years by ketosis-resistant diabetes mellitus. A 3~2-year-old girl with this syndrome has been studied in an attempt to delineate the mechanisms involved in the condition. Intravenous radiopalmitate was found to be incorporated into serum triglycerldes in increased amounts when she was lipemic. Epinephrine administration did not result in a rise in serum free fatty acids (FFA). The serum FFA level fell with exogenous insulin but not with tolbutamide, whereas the glucose response was similar. The response to intravenous heparin indicated a normal serum lipoprotein lipase. Intravenous labeled norepinephrine revealed a marked increase in normetanephrine excretion. Leukocyte triglyceride formation and phospholipid incorporation from labeled palmitate, tripalmitin, BOH, and glucose were normal. In contrast to the normal, insulin inhibited palmltate and B O H oxidation by white blood cells. Ketosteroid excretion was intermittently elevated. Assay of serum insulin and growth hormone levels is in progress. The results are informative: of tile role of adipose tissue in fatty acid metabolism and the role of the liver in hyperlipemia. Abnormalities of epinephrine metabolism should be investigated in other cases of hyperlipemia. The possibility of an abnormal insulin with altered pituitary feedback is suggested.
61. Studies of active transport of calcium, magnesium, and sulfate by the small intestine Constantine Anast, Robin Kennedy, ~ George Volk, "~ and Lueile Adamson, ~ Department of Pediatrics, University of Missouri School of Medicine, Columbia, Mo. Observations were made of the active transport of calcium, magnesium, and sulfate in the small intestine of the rabbit utilizing the everted
Abstracts
1 10 5
gut-sac technique of Wilson and Weisman. The most active transport of sulfate occurred in the distal third of the small intestine. Sulfate was not found to be actively transported in the proximal small gut and relatively little transport occurred in the midgut. Dinitrophenol ( D N P ) , anaerobiosis, and ouabain (10 -5 M) all inhibited active transport of sulfate. Active transport was almost completely inhibited when lithium chloride, potassium chloride, rubidium chloride, cesium chloride, choline chloride, or Tris buffer was substituted for sodium chloride in equimolar concentrations (120 mM.) in the standard buffer medium. In contrast to sulfate, calcium was found to be actively transported only in the proximal small gut. Anaerobiosis, DNP, and ouabain (I0 -s M but not 10 -2 M) inhibited active transport. Inhibition resulting when LiC1, NH~C1, KC1, RbC1, or CsC1 was substituted for NaC1 in the standard buffer medium appeared to be related to the atomic weight of the cation; the smaller the atomic weight, the greater the inhibition. Of the five inorganic univalent cations studied, only cesium with the greatest atomic weight failed to inhibit the active transport of calcium. Transport of calcium increased progressively as sodium was increased and lithium decreased, with the sum of sodium and lithium held constant at 120 raM. Magnesium, unlike calcium and sulfate, was not actively transported by any segment of the small intestine. Neither was active transport of magnesium observed in intestinal segments from magnesium-deficient animals.
62. Multiple amino acid carrier systems in plasma membranes: Genetic implications Charles R. Striver and Onslow H. Wilson, ~" McGill University and Montreal
Children's Hospital, Montreal, Quebec From evidence from heritable diseases and infusion experiments in mammals, amino acid transport mechanisms can be divided into four groups: (1) cyclic and neutral aliphatic amino acids, except group 2; (2) imino acids and glycine; (3) "dibasics" and cystine; (4) dicarboxylics. The "'common" transport mechanisms of the second and third groups were studied in detail. Male hooded rats were infused with individual amino acids of both groups; only intragroup competition for renal absorption occurred. In vitro studies measuring uptake of labeled amino acids into rat kidney cortex slices were then performed and transport kinetics (Michaelis-Menten) were analyzed. T h e K m and Ki values for each amino acid were used to describe its relation to the sites at which it acted as substrate and as competitive inhibitor. In addition to the division into two major groups, an individual transport site, with its own specificity characteristics, was found for each amino acid in the two groups. Therefore a single mutation affecting group transport (e.g., cystinuria) would affect multiple