Comparative Diabetogenic Action of the Hypophysis From Various Animals

Abstract

The r51e of the anterior portion of the hypophysis in the production or intensification of diabetes was discovered in this Institute in 1929 and 1930 and since then has been studied continuously. An abstract of this work up to 1935 was published by Houssay in 1936. Some of the extracts of anterior hypophysis in animals without hypophysis and pancreas and with mild diabetes, intensified the hyperglycemia and glycosuria to a degree exceeding the intensity of the diabetes associated with pancreatectomy alone. This was observed in the toad , and in the dog Houssay, Biasotti, Di Benedetti, and Rietti, 1932). These latter observations suggested a possible method of biological assay of the diabetogenic factor. The present experiments were undertaken to demonstrate the relative potency of the diabetogenic principle in extracts of the anterior hypophysis from various species.Te st A nimals (a) Dogs.--The hypophysectomized-pancreatectomized dog is difficult to maintain in good condition because the injection of anterior hypophyseal extract profoundly aggravates its condition. On the other hand insulin cannot be used since they are so sensitive to this agent they develop fatal hypoglycemia from doses as low as 1 to 3 units per day. Normal dogs, while not showing this marked insulin sensitivity, require such large amounts of anterior hypophyseal extract (between 1 and 2 gin. per kilo per day for several days) as to prohibit its extensive use for titrating the diabetogenic principle. Mention should be made that this diabetes in normal dogs, characterized by hyperglycemia, ketonemia, hyperlipemia, acidosis, etc., (Houssay, 1936) is produced specifically by anterior hypophyseal extracts, extracts of other organs being inert. The hyperglycemia which is preceded and accompanied by increased insulin resistance, appears between the 2nd and 5th days after starting with the injections. Upon discontinuing the injections, blood sugar returns to normal in 1 to 3 days. If the animal fasts, the injections produce insulin resistance without hyperglycemia.Dogs with subtotal pancreatic resection demonstrate Sandmeyer's diabetes if less than 3 gin. of pancreas are left. This attenuated diabetes is not permanent since it 93 on

11β-Hydroxysteroid Dehydrogenase 1: Translational and Therapeutic Aspects

“…Formative work in the 1930s and 1940s by Houssay et al (64) and Long and Lukens (65) first described a role for glucocorticoids in the regulation of carbohydrate metabolism and the development of diabetes. Subsequently, Ingle (66,67) and Long (68) illustrated that glucocorticoids stimulate gluconeogenesis, inhibit glucose utilization, and cause insulin resistance.…”

Effects of Total Hypophysectomy on the Glycemic and Plasma Cholesterol Levels in the Snake,Natrix piscator(Russell)

“…Dome (1943) demonstrated that anterior pituitary tissue (54 lobes each in two days) had no effect on the blood sugar of the unoperated toads but is very active in the depancreatized animals. The human hypophysis on the other hand, produced a diabetogenic action in the normal dog on daily doses of 1.26 mg/kg/ day for two days (Houssay et al 1942). I t appears that the absence of the diabetogenic action following administration of pituitary tissue in the snake under study as also in the toads investigated by Dosne may be due to the opposing action of the endogenously produced insulin in the intact pancreases of these animals.…”

“…It is well known that the pituitary hormones have a regulatory influence on the carbohydrate metabolism (Houssay 1936(Houssay , 1942Houssay et al 1942 andDe Bod0 andAltszuler 1958). Hypophysectomy alone is known to produce a fall in blood sugar level in most vertebrate species examined (Mahoney 1934;Soskin et al 1935;Russell 1936;Slome 1936;Foglia ,et al 1955;Miller and Wurster 1958;Houssaf andPenhos 1960 andRangneker andSabnis 1966 a &b ) .…”

“…Hypophysectomy alone is known to produce a fall in blood sugar level in most vertebrate species examined (Mahoney 1934;Soskin et al 1935;Russell 1936;Slome 1936;Foglia ,et al 1955;Miller and Wurster 1958;Houssaf andPenhos 1960 andRangneker andSabnis 1966 a &b ) . Houssay (1942Houssay ( , 1959 and Some (1936) have noted that in toads the anterior pituitary has a diabetogenic action which is independent of the interrenal tissue. Wurster and Miller (1960) have demonstrated the absence of pituitary hyperglycemic factor of any significance in the salamander.…”

A Histochemical Study on the Influences of Hypophysis-Adrenal System upon Alkaline Phosphatase

“…Cavallero (1953) and Abrams (1953) reported the proliferation and hyperfunction of pancreatic alpha cell by growth hormone administration"1),"). Houssay (1942) reported concerning the diabetogenic action of growth hormone upon alloxan diabetic animal and hyperglicemic factor on the normal animal, and Anselmino(1933) and Hofmann (1933)' ") reported the hypoglycemic factor and pancreaticotropic factor of growth hormone. Marks (1940) reported that the repeated administration of growth hormone increases the amount of insulin in pancreas islet and Anselmino showed the excitment effect on the islet, showing the increase of pancreatic islet in number and But Bryans (1952) denied the existence of such pancreaticotropic hormone, showing that after hypophysectomy the normal pancreatic islet did not show any shrinking").…”