Lillian Recant

Failure of hypophysectomy, adrenalectomy or thyroidectomy to affect response of non-esterified fatty acids to fasting.

Summary There is no evidence of diurnal variation of plasma NEFA levels in rats. Hypophysectomized, adrenalectomized and thyroidectomized animals show significantly lower plasma NEFA values than normal rats either when food is provided ad lib. or after fasting. After 16 hour fast, both normal and operated rats show marked increase in plasma NEFA levels. It is probable that the mechanism involved in NEFA response to fasting is not controlled by pituitary, thyroid or adrenal hormones.

Effects of N-Ethyl Maleimide and Insulin upon Adipose Tissue

Summary N-ethyl maleimide, a sulfhydryl blocking agent, is capable of inhibiting the response of adipose tissue to insulin. The inhibitory mechanism is not competitive. Although the effect appears to be upon the cell surface, the binding of insulin to the tissue is not impaired.

STUDIES ON THE MECHANISM OF TOLBUTAMIDE HYPOGLYCEMIA IN ANIMAL AND HUMAN SUBJECTS

Since 1942 there has accumulated an increasingly impressive body of scientific evidence indicating that the sulfonylurea compounds are extremely effeclive hypoglycemic agents in both human and animal subjects.’ The potential usefulness of these drugs in the management of patients with diabetes has provided the stimulus for innumerable clinical trials. However, the fundamental question regarding the mechanism of this hypoglycemic action has not yet been answered. It is obvious t‘lat a full understanding of this mechanism is of more than academic interest. Although many classes of drugs may produce hypoglycemia, the usefulness of such drugs as therapeutic agents in diabetes must be dependent upon more than a hypoglycemic action. There must be, in addition, an enhancement of the over-all metabolism of carbohydrate. In order to evaluate the potential therapeutic benefits that may be derived from the sulfonylureas, it becomes important, first, to understand the mechanisms by which the hypoglycemia is produced and, second, to measure certain parameters that might reflect alterations in metabolic processes known to be deranged as a consequence of impaired carbohydrate utilization. The experiments to be described were designed to study the action of tolbutamide in animal and human subjects, within the framework of the concepts noted. Since hypoglycemia may result from a decreased release of glucose from the liver, an increased utilization of glucose in the peripheral tissues, or a combination of the two, an effort was first made to determine the major locus of tolbutamide action. The evidence to be presented supports a hepatic mechanism of action. In order to determine the effect of tolbutamide upon over-all carbohydrate metabolism, studies were made of amino acid incorporation into liver protein, a metabolic system known to be dependent upon adequate utilization of carbohydrate within the liver.2 An enhancement of the protein “synthetic” mechanisms in liver following tolbutamide therapy was found. These observations suggest that tolbutamide decreases the release of glucose from the liver, while a t the same time increasing the over-all glucose utilization by that tissue.

Effect of the insulin-inhibitory albumin fraction from normal and diabetic subjects on adipose tissue

Abstract Plasma albumin obtained from normal and diabetic subjects inhibits insulin action on muscle. Diabetic albumin is inhibitory at lower concentrations than normal albumin. These preparations stimulate rather than inhibit insulin action on adipose tissue and contain endogenous insulin. In addition, they have a noninsulin stimulatory action on glucose metabolism of fat tissue.

Negative Feedback Mechanism of Cholesterol Synthesis in Experimental Nephrosis.

Summary Feeding of cholesterol resulted in marked inhibition of hepatic cholesterol synthesis in nephrotic and normal animals. A faulty hepatic feedback mechanism cannot be invoked to explain nephrotic hypercholesterolemia.

Structural analogues of puromycin in production of experimental nephrosis in rats.

Summary Of 5 structural analogues of Puromycin that were investigated, only one, 6-dimethyl-amino-purine-3-amino-d-ribo-side, produced a nephrotic syndrome in rats. The specific structural configuration necessary to induce this syndrome is discussed.

Glomeruläre Fermente bei zwei verschiedenartigen Formen von Nephrose

ZusammenfassungUntersuchungen am isolierten Rattenglomerulum haben eine verminderte alkalische Phosphatase-Aktivität und eine vermehrte Glucose-6-Phosphat Dehydrogenase-Aktivität bei der experimentellen Nephrose aufgezeigt.Diese Veränderung ist durch die folgenden Besonderheiten gekennzeichnet:1.Sie kann sowohl in der Aminonucleosid (nichtimmunologische Form) wie auch in der Anti-Ratten-Nieren-Kaninchen-Serum-Nephrose (immunologische Form) beobachtet werden.2.Die Veränderungen sind erst nach der Entwicklung der Proteinurie zu beobachten. Sie verstärken sich mit zunehmender Proteinurie.3.Sie sind organspezifisch: andere Gewebearten (Leber und Pankreas) weisen andersartige enzymatische Veränderungen auf. Zur Zeit ist es nicht möglich zu bestimmen, ob das gefundene glomeruläre Fermentmuster einer spezifischen Läsion bei der Nephrose entspricht, oder ob es den Auswirkungen des Proteinverlustes im Glomerulum zugeschrieben werden kann.

Effect of 6-Dimethylaminopurine-3-Amino-D-Ribose on Adenosine Triphosphate Formation in Yeast.

Summary Production of acid-labile phosphate by crude brewers yeast system, in the presence of adenosine and inorganic phosphate, has been demonstrated. This acid-labile phosphate has been identified as adenosine triphosphate. The nucleoside, 6-dimethyl-aminopurine-3-amino-d-riboside inhibits adenosine triphosphate formation in this system. The possible relationship of this inhibitory action to ability of the nucleoside to produce nephrosis in rats is discussed.

Sequence of development of hypercholesterolemia and hypoproteinemia in aminonucleoside nephrosis.

Summary The sequence of development of hypoproteinemia and hypercholesterolemia was studied in 15 aminonucleoside nephrotic animals. Hypercholesterolemia succeeds rather than precedes hypoproteinemia.

Renale Fermentausscheidung bei der Aminonucleosid-Nephrose

ZusammenfassungMalatdehydrogenase (MDH) mit einem Molekulargewicht von 40000 aus endogener Quelle und exogen durch intraperitoneale Injektion zugeführt wird als Maß der makromolekulären Permeabilität des Glomerulums von experimentell nephrotischen (Aminonucleosid) und gesunden Ratten verwendet.Eine deutliche endogene und exogene MDH-Aktivitätszunahme im Urin findet sich erst dann, wenn die Proteinurie 100 mg/24 Std übersteigt. Diese Beobachtung spricht gegen die Möglichkeit einer langsam sich vergrößernden Filteröffnung im Glomerulum mit Durchlaß des MDH-Moleküls vor dem Albumin. Ein selektiver Vorgang für eine erhöhte Permeabilität von Albumin wird angenommen.