뇌하수체, 부신 및 갑상선剔出이 膵小島에 미치는 영향

Abstract

[영문]

Until the discovery of the islets by Langerhans in 1869 the pancreas was regarded solely as an exocrine gland. The endocrine function of the islets, however, was first suggested by Laguesse in 1904.

Von Mering and Minkowski in 1889 noted that the pancreas regulate carbohydrated metabolism based on the observation of the development of diabetes in pancreatechomized dogs, but they attributed this effect to the function of exocrine pancreas. Hedon(1893), however, proved that regulation of sugar metabolism by the pancreas is dependent on its endocrine function through the observation of transplantation experiment of the pancreas after the main pancreas was removed.

Lane(1907) and Bensley(1911) succeded to differentiate two types of cells, A and B, in the langerhans islets by special staining methods, and Homans(1914, 1915) noticed that B-cells are involved in experimental diabetes and attributed sugar regulating function to B-cells in the islets.

Discovery of insulin in 1921 and selective destruction of B-cells leading to diabetes by the administration of alloxan by Dunn et al. in 1943 appeared to conclude the study of the etiology and treatment of diabetes. But it soon became clear that the etiology of diabetes is not so simple as previously regarede, and many other factors besides islets of the pancreas are involved in the development of diabetes, particularly the hypophysis and adrenals. Furthermore, the changes in the Langerhans islets are geing regarded to be secondary to the changes in blood sugar level rather than a primary lesion(Houssay et al. 1932, Lukens and Dohan 1942, Colowick et al. 1947, Long et al. 1940, Levine et al. 1950, Ashmore 19640.

The present investigation is aimed to study the effect of hypohysectomy, adrenalectomy, and thyroidectomy on the Langerhans islets of the pancreas to find any relationship between the islets of Langerhans and other endocrine organs.

Materials and Methods

Albino rats weighing around 200 gms were used for the experiments and divided into four groups as follow:

Group Ⅰ : Normal control (7)

Group Ⅱ : Hypothysectomy (40)

Group Ⅲ : Adrenalectomy (50)

Group Ⅳ : Thyroidctomy (35)

Hypothysectomy was performed by the transauricular aspiration method of Falconi and Rossi (1964). The adrenals were removed after the exposure of the kidney and adrenals retroperitoneally thought the incision from the back along 1cm distance from the vertebral column on each sides. The thyroids were removed through the incision at midline of the anterior neck after separating and leaving parathyroid glands with as little as the thyroid tissue is included . All operative procudures were carried out under ether anesthesia with aseptic precautions.

Animals were fed with a mixture of 3 parts of wheat, 2 parts of barley, 1 part of corn, and 0.1% of powder milk and fish. For adrenalectomized animals 1 gm% salt water were given. For hypophysectomized animals cortisone was given intramuscularly

once a day for 5 days in a dose of 10mg/kg of body weight.

Postmortem examinations were made in shortest time when the animals died, and the remaining animals were killed and necropsied on the 6th, 20th, and 40th day in adrenalectomized group, on the 20th and 40th day in thyroidectomized group, and the 20th, 35th, and 55th day in hypophysectomized group. At necropsy, the adequacy of the hypophysectomy, darenalectomy, and thyroidectomy was checked. Then the pancreas, heart, liver and skeletal muscles were removed and fixed in 10% neutral formalin. Microsections were prepared in 6-μ thickness after paraffin embeding and stained all sections with hematoxylin and eosin. In additon, sections of the pancreas were stained with Gomori's aldehyde-fuchsin(1950) method to study beta-cells in Langerhans islets, and sections of the liver, heart and skeletal muscle were stained with periodic acid-Schiff's reaction and periodic acid-Schiff's reaction method after diastase digestion, to estimate glycogen contents of each organs.

Blood sugar determinations were made in normal control, adrenalectomy and thyroidectomy groups by the method of Somogy and Nelson(1953).

Results and Discussion

A. Survival period of animals in each experimental group:

Over 50% of animals in each group died within 3 days following hypophysectomy, adrenalectomy or thyroidectomy. Of these over 70% died immediately or within one day after the operation. Numbers of animals survived more than 20 days were 15 out of 40 in hypophysectomy group(37.5%), 8 out of 50 in adrenalectomy group (16%), and 50 out of 35 in thyroidectomy group(43%).

B. Alterations of blood sugar level:

Average normal blood sugar level in control group was 72.0±3.4mg%. It declined to 38.0±4.8mg% at the 6th day, 45.6±0.54mg% at the 20th day and 46.6mg% at the 40th day after adrenalectomy. In thyroidectomy group it fell to 53.6±5.8mg% at the 20th day and 51.5±5.9mg% at the 40th day following the thyroid was removed.

C. Histologic alterations of the Lagerhans islets of the pancreas: Hypophysectomy mduced generalized and individual cell atrophy of the islets with pyknosis of individual nuclei at the 20th day and 35th day. But they became slightly enlarged and unclear pyknosis disappeared at the 55th day after the removal of the pituitary gland. The relative numbers of beta-cells to others

increased slightly during the 20th and 35th day following the hypophysectomy, but returned to aratio equivalent to normal control group at the 55th day. The amount of beta-granules decreased slightly after the 35th day.

Adrenaletomy induced cloudy swelling of beta-cells until the 5th day followed by atrophy and nuclear pyknosis from the 6th day. The ratio of beta-cells gradually increased from the 3th beta-granules also increased and concentrated within cytoplasm at the 6th day after adrenalectomy.

Thyroidectomy induced rather minor changes in the islets and showed slight but generalized atrophy of the islets with light increase of beta-cell ratio to other cells.

D. Changes of glycogen contents in the liver, cardiac muscle and skeletal muscles

Hepatic glycogen decreased throughout the period of observation in the hypophysectomy group, but decreased markedly during the first 20 days followed by gradual increase in adrenalectomy group, and decreased slight to moderately throughout the couse in thyroidectomy group. Glycogen in cardiac muscle was negligible in all groups and no notable alteration was found. Glycogen in skeletal muscle was rather scanty in amount in control group. It decreased in hypophysectomy and adrenalectomy groups.

Summary

The results obtained by the present investigation showed decrease of blood sugar, atrophy of beta-cells in the Lagerhans islets of the pancreas with temporary accumulation of beta-granules and marked decrease of hepatic glycogen contents.

These changes seemed to be readjusted as the time proceed following the removal of each organs. The changes in the beta-cells are likely secondary to the decreased blood sugar level, but the possibility of direct action of normone from the pituitary, adrenals, and thyroid on beta-cells can not be assesed with present results.