Measurements of insulin activities in pancreas and serum of mice with spontaneous (“obese” and “New Zealand obese”) and induced (goldthioglucose) obesity and hyperglycemia,with considerations on the pathogenesis of the spontaneous syndrome

Summary 1. Insulin-like activity (ILA) and immunoreactive insulin (IRI) of pancreatic extracts and of serum have been measured in lean and obese (obob) mice from the Jackson Memorial Laboratory in Bar Harbor, Maine; in New Zealand obese mice; and in goldthioglucose-obese Swiss mice, and their lean controls. In all three types of mice the relative amounts of suppressible and nonsuppressible insulin activities of serum have also been established. — 2. Pancreatic content of IRI in (obob) mice is much greater than in their lean sibblings at five months of age, but smaller at 5 weeks, whereas serum IRI and ILA of (obob) mice are greatly in excess of the same activities of serum from their lean littermates at both ages. It is suggested that increased peripheral demand for insulin preceeds increased insulin synthesis and storage in this type of obesity. — 3. In all three strains of mice, obese or lean, the ratio of biologic to immunologic activity of pancreatic extracts was constant and close to unity. In serum, this ratio was also constant but approximately five times greater than unity. These findings do not support the notion that differences in insulin structure might account for differences in the biological activity of insulin in obese and non-obese animals; they are in keeping with the concept of a potentiation of serum insulin activity by some component of serum in all mice. — 4. Approximately 90% of serum ILA in all three types of obese mice studied was suppressed in the presence of anti-insulin serum, although the absolute levels of non-suppressible ILA were similar to those reported for other species. It is unlikely, therefore, that bound insulin accounts for a significant part of the increased ILA of serum of any of the three types of obese animals studied. — 5. Present data support the concept of a marked tissue-bound muscular resistance to insulin action as an important, possibly primary pathogenetic feature in (obob) mice. A similar, but much less marked muscular resistance can be demonstrated in NZO mice, whereas muscular resistance to insulin action is totally absent in goldthioglucose obese Swiss mice after a 24 hour fast.This work was supported by the Fonds National Suisse de la Recherche Scientifique (Grant No. 3618), Berne, Switzerland, the Fondation Emil Barell pour le développement de la recherche médico-scientifique, Basel, Switzerland, and the Diabetes Foundation, Inc., Boston, Massachusetts. Dr.Lambert is aspirant of the Fonds National Belge de la Recherche Scientifique.