Islet lysosomal enzyme activities and plasma insulin levels in obese hyperglycemic mice following injection of the lysosomotropic drug suramin.

The pattern of islet lysosomal enzyme activities and the plasma levels of insulin and glucose were studied in adult obese hyperglycemic mice (aged 6-8 months) after in vivo administration of the lysosomotropic drug suramin. After suramin administration, 5.2 mumol/mouse, at time 0 and at 18 hr, the plasma insulin levels in the obese mice gradually decreased and were reduced by about 85% at 20 hr. At the same time point the suramin-induced inhibition of insulin secretion was reflected by a notable (250%) increase in islet insulin content. A negative correlation (r = -0.81; p less than 0.01) was observed between plasma insulin level and islet insulin storage. The plasma glucose levels were not affected by the drug. Furthermore, it was observed that the islet activity of the glucose producing glycogenolytic hydrolase, acid amyloglucosidase, which is excessively high in the obese mouse, was markedly reduced by suramin (about 70%) at 20 hr. A good correlation (r = 0.88; p less than 0.001) was found to exist between the islet acid amyloglucosidase activity and the plasma insulin concentration in controls and suramin-treated mice. When glycogen was replaced by maltose or 4-methylumbelliferyl-alpha-D-glucoside as substrate for the acid alpha-1,4-glucoside splitting activity the inhibitory effect of suramin was less pronounced (about 50%). The ratio, glycogen splitting/maltose splitting activity in islet tissue was reduced by suramin from 1.25 +/- 0.12 (control) to 0.69 +/- 0.06 (p less than 0.005). The neutral, nonlysosomal alpha-1,4-glucoside splitting activity was not affected by the drug.(ABSTRACT TRUNCATED AT 250 WORDS)