Differential changes in islet lysosomal enzyme activities in aging obese hyperglycemic mice

The pattern of pancreatic islet lysosomal enzyme activities was investigated in adult obese mice (aged 5-7 months), old obese mice (aged 9-17 months) and aged-matched old "obese" mice suffering from excessive weight loss. A series of lean NMRI mice of comparable age was included as controls. It was observed that the islet activity of the glucose producing glycogenolytic hydrolase, acid amyloglucosidase, was excessively high in the adult obese mouse, being about 10 times higher than in the adult lean mouse. This high activity was reduced by about 65% in the islets of old obese mice and by about 80% in old mice suffering from weight loss. When glycogen and maltose were compared as substrates for the alpha-1,4-glucoside splitting activity, the ratio, glycogen splitting/maltose splitting activity in adult obese mice (1.68) showed amyloglucosidase predominance, whereas the ratio in old obese mice (0.67), and in old mice suffering from weight loss (0.79) revealed a significant change in this relation. The extremely elevated plasma insulin levels in the adult obese mice were reduced by about 65% in old obese mice and by about 95% in old mice with excessive weight loss and thus displaying the same pattern as islet amyloglucosidase activity. Further, in normoglycemic obese mice a highly significant correlation (r = 0.85; p less than 0.001) was found between islet acid amyloglucosidase activity and the actual insulin secretory rate as reflected by the plasma insulin concentrations. The activity of islet N-acetyl-beta-D-glucosaminidase showed an activity pattern opposite to that of acid amyloglucosidase.(ABSTRACT TRUNCATED AT 250 WORDS)