Pathogenetic aspects of the obese-hyperglycemic syndrome in mice (genotypeobob): II. Extrapancreatic factors

The cause of the pronounced insulin resistance of the hereditary obese-hyperglycemic syndrome in mice (obob) is so far unknown. To evaluate whether growth hormone (GH) is of pathogenetic significance in this context thein vivo incorporation of sulfate into costal cartilage was measured in obese-hyperglycemic mice and their lean littermates at various ages. It was found that a) GH administration raised the sulfation activity of the costal cartilage in both types of mice; b) the hormone further increased the insulin resistance of the obesehyperglycemic animals; c) the sulfate incorporation of the obese mice was considerably elevated after 1 month of age and remained high until the age of about 10 months. In 17 months old animals it had returned to a level similar to that of the lean littermates. In addition, the epiphyseal width of the tibia was increased in the obese mice. Since it was not clear whether the increased rate of sulfate in corporation was due to an elevated endogenous GH activity and/or the high serum insulin levels prevailing in the obese mice at this period of life a study of the pituitary morphology was carried out. The lack of obvious structural or quantitative differences between the pituitary alpha cells of the lean and obese mice did not exclude the possibility that the elevated sulfation activity was caused by the high serum insulin levels rather than an increased circulating GH activity. — Glucokinase activity, characterized by a highK m value, was found in the livers of both lean and obese mice. A significant elevation of this enzyme activity, but not of the hexokinase activity, in the obese mice strongly suggests that the insulin resistance does not extend to the liver cells in the obese-hyperglycemic syndrome.