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Albert Salehi

S Albert Salehi

Research team manager

Albert Salehi

Islet glucan-1,4-alpha-glucosidase : differential influence on insulin secretion induced by glucose and isobutylmethylxanthine in mice

Author

  • A Salehi
  • I Lundquist

Summary, in English

In previous in-vivo studies we have presented indirect evidence for the involvement of islet acid glucan-1,4-alpha-glucosidase (acid amyloglucosidase), a lysosomal glycogen-hydrolysing enzyme, in certain insulin secretory processes. In the present combined in-vitro and in-vivo investigation, we studied whether differential changes in islet acid amyloglucosidase activity were related to the insulin secretory response induced by two mechanistically different secretagogues, glucose and isobutylmethylxanthine (IBMX). It was observed that addition of the selective alpha-glucosidehydrolase inhibitor emiglitate (1 mmol/l) to isolated pancreatic islets resulted in a marked reduction of glucose-induced insulin release. This was accompanied by a pronounced suppression of islet activities of acid amyloglucosidase and acid alpha-glucosidase, whereas other lysosomal enzyme activities, such as acid phosphatase and N-acetyl-beta-D-glucosaminidase, were unaffected. Furthermore, islets first incubated with emiglitate in the presence of high (16.7 mmol/l) glucose released less insulin than untreated controls in response to glucose in a second incubation period in the absence of emiglitate. In contrast, IBMX-induced insulin release was not influenced by emiglitate although accompanied by a marked reduction of islet activities of all three alpha-glucosidehydrolases. Basal insulin secretion (1 mmol glucose/l) was unaffected in the presence of emiglitate. In-vivo pretreatment of mice with highly purified fungal amyloglucosidase ('enzyme replacement'), a procedure known to increase islet amyloglucosidase activity, resulted in a greatly enhanced insulin secretory response to an i.v. glucose load. The increase in insulin release was accompanied by a markedly improved glucose tolerance curve in these animals. In contrast, enzyme pretreatment did not influence the insulin response or the blood glucose levels after an i.v. injection of IBMX. The data lend further support to our hypothesis that islet acid amyloglucosidase is involved in the multifactorial insulin secretory processes induced by glucose but not in those involving direct activation of the cyclic AMP system. The results also indicate separate, or at least partially separate, pathways for insulin release induced by glucose and IBMX.

Department/s

  • Diabetes - Islet Patophysiology
  • Islet cell physiology
  • Department of Experimental Medical Science

Publishing year

1993-09

Language

English

Pages

391-400

Publication/Series

Journal of Endocrinology

Volume

138

Issue

3

Document type

Journal article

Publisher

Society for Endocrinology

Topic

  • Endocrinology and Diabetes

Keywords

  • 1-Deoxynojirimycin
  • 1-Methyl-3-isobutylxanthine
  • Animals
  • Drug Interactions
  • Female
  • Glucan 1,4-alpha-Glucosidase
  • Glucosamine
  • Glucose
  • Insulin
  • Insulin Antagonists
  • Islets of Langerhans
  • Kinetics
  • Lysosomes
  • Mice
  • Mice, Inbred Strains
  • Journal Article
  • Research Support, Non-U.S. Gov't

Status

Published

Research group

  • Diabetes - Islet Patophysiology
  • Islet cell physiology

ISBN/ISSN/Other

  • ISSN: 0022-0795