title: The relationship of islet amyloglucosidase activity and glucose-induced insulin secretion.
abstract: We have previously presented evidence for the involvement of islet acid amyloglucosidase, a lysosomal glycogen-hydrolyzing enzyme, in certain insulin secretory processes. In the present investigation, we studied whether differential changes in islet amyloglucosidase activity could be related to the insulin secretory response to glucose. It was observed that the dose-response curve for glucose-induced insulin response in vivo was shifted to the left by pretreatment of mice with purified fungal amyloglucosidase. In enzyme-pretreated mice, the ED50 was 2.1 mmol/kg glucose as compared with 5.7 mmol/kg in saline-pretreated controls (p less than 0.005). Also, the maximal insulin response to glucose was enhanced by amyloglucosidase pretreatment. Parenteral administration to mice (four injections during 2 days) of the pseudotetrasaccharide acarbose, a recognized inhibitor of intestinal alpha-glucosidases, surprisingly induced a marked increase in the activities of islet acid amyloglucosidase (+ 120%; p less than 0.001) and acid alpha-glucosidase (+ 45%; p less than 0.01) without affecting the activities of other lysosomal enzymes such as acid phosphatase and N-acetyl-beta-D-glucosaminidase. No effect on the microsomal neutral alpha-glucosidase was recorded. Moreover, in these mice, the insulin secretory response to glucose was enhanced both at a maximal dose of glucose 11.1 mmol/kg and at a dose in the ED25-ED50 range, 3.3 mmol/kg (p less than 0.005). Direct addition of acarbose to islet homogenates strongly suppressed acid amyloglucosidase activity, the EC50 being approximately 1 microM. Acid alpha-glucosidase activity was also strongly inhibited, whereas the activities of acid phosphatase and N-acetyl-beta-D-glucosaminidase were unaffected. Neutral alpha-glucosidase was slightly suppressed.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Department of Cell Biology, Faculty of Health Sciences, University of Linköping, Sweden.
authors.forename: I
authors.initials: I
authors.lastname: Lundquist
authors.forename: G
authors.initials: G
authors.lastname: Panagiotidis
mesh_terms: D020909:Acarbose; D000818:Animals; D001481:Basal Metabolism / Q000187:drug effects; D005260:Female; D005656:Fungal Proteins / Q000378:metabolism*; D005087:Glucan 1,4-alpha-Glucosidase / Q000378:metabolism*; D005947:Glucose / Q000494:pharmacology*; D065089:Glycoside Hydrolase Inhibitors; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000201:enzymology*; D008247:Lysosomes / Q000201:enzymology; D051379:Mice; D008815:Mice, Inbred Strains; D014312:Trisaccharides / Q000494:pharmacology
chemical_list: D005656:Fungal Proteins; D065089:Glycoside Hydrolase Inhibitors; D007328:Insulin; D014312:Trisaccharides; D005087:Glucan 1,4-alpha-Glucosidase; D005947:Glucose; D020909:Acarbose