Lysosomal glycogen storage mimicking the cytological picture of Pompe’s disease as induced in rats by injection of an α-glucosidase inhibitor

The Pseudotetrasaccharide Acarbose Inhibits Pancreatic Islet Glucan-1,4-α-glucosidase Activity in Parallel With a Suppressive Action on Glucose-Induced Insulin Release

“…In contrast, we have found previously (26) that the enzyme inhibition curve, when using another selective a-glucoside hydrolase inhibitor, the deoxynojirimycin derivative miglitol, was almost identical to the inhibition curve for insulin release. The explanation for this discrepancy is most probably the following: Miglitol is readily transported into cells, whereas the pseudotetrasaccharide acarbose is taken up by endocytosis (11,13). This means that miglitol can be considered to be uniformly distributed within the whole cell, whereas acarbose is concentrated in the vacuolar system.…”

“…Very recently, we found that repeated injections of acarbose to mice during two consecutive days induced changes in islet glucan-l,4-a-glucosidase activity that were accompanied by similar changes in the insulin secretory response to an intravenous glucose load (8). Moreover, previous studies have shown that parenteral administration of acarbose to rats induced hepatic lysosomal glycogenosis as assessed histochemically and cytochemically (13). This effect is thought to be achieved by acarbose molecules being taken up by endocytosis in the liver and transferred to the lysosomal apparatus, where acarbose can inhibit the glycogenolytic hydrolases (13).…”

“…Moreover, previous studies have shown that parenteral administration of acarbose to rats induced hepatic lysosomal glycogenosis as assessed histochemically and cytochemically (13). This effect is thought to be achieved by acarbose molecules being taken up by endocytosis in the liver and transferred to the lysosomal apparatus, where acarbose can inhibit the glycogenolytic hydrolases (13). Thus, in the present context, acarbose has two unique features: 1) it is a selective a-glucoside hydrolase inhibitor; and 2) its action within the cell is presumably restricted to the vacuolar apparatus.…”

Effects of Bay m 1099, an α-Glucosidase Inhibitor, on Starch Metabolism in Germinating Wheat Seeds

“…Blocking the breakdown of oligosaccharides by intestinal a-glucosidase, these sugar analogs are expected to be anti-hyperglycemic drugs for diabetes and obesity.14-16) These analogs also inhibit lysosomal acid ct-glucosidase to accumulate glycogen in lysosomes, mimiking the cytological and biochemical feature of type II glycogenosis (Pompe's disease). [17][18][19] Bay m 1099 and acarbose also strongly inhibit plant tissue a-glucosidases in vitro. 20 ) In this paper, we describe for the first time the effects of Bay m 1099 on starch metabolism in germinating wheat seeds.…”

Pharmacology of Glucosidase Inhibitors

“…A number of experiments have been done to simulatc Iysosomal glycogen storage (Pompe's disease), predominantly by parenteral administration of excessive doses of acarbose, miglitol and emiglitate (CALDER and GEDDES 1989;GEDDES et al 1983;GEDDES and TAYLOR 1985a;KONISHI et al 1989;KONISHI et al 1990;LEMBCKE et al 1991;LUELLMANN-RAUCH 1981;LUELLMANN-RAUCH 1982;LUELLMANN-RAUCH and W A"I'ERMANN 1(87). It was shown that inhibition of the Iysosomal acid 1,4-glucosidase was followed by an increased lysosom al content of glycogen in various organs under these experimental conditions.…”