Islet lysosomal enzyme activities and glucose-induced insulin secretion: effects of mannoheptulose, 2-deoxyglucose and clonidine.
In previous investigations we have shown a striking relationship between the activity of glycogenolytic glucose producing acid hydrolases in pancreatic islet tissue and certain insulin-releasing processes. In the present investigation we have studied the relation between islet lysosomal enzyme activities and glucose-induced insulin secretion in vitro in the presence of various insulin secretory inhibitors. It was observed that the nonmetabolizable glucose analogue, mannoheptulose (5 mmol/l) did induce a 2-fold increase in insulin release at low (1 mmol/l) glucose, and a total suppression of insulin release at high (16.7 mmol/l) glucose. These changes in the insulin-secretory pattern were accompanied by similar changes in the activity of islet acid alpha-glucosidase. The activities of neutral alpha-glucosidase (endoplasmic reticulum) or acid phosphatase and N-acetyl-beta-D-glucosaminidase (lysosomes) were not affected by mannoheptulose. 2-Deoxyglucose (5 mmol/l), another glucose analogue, did not increase insulin secretion or acid alpha-glucosidase activity at low glucose. At high glucose, however, a partial inhibition of both insulin release (approximately 50%) and acid alpha-glucosidase activity was seen. 2-Deoxyglucose slightly suppressed acid phosphatase activity but did not influence the activities of neutral alpha-glucosidase or N-acetyl-beta-D- glucosaminidase. Direct addition of glucose to islet homogenates showed a suppressive effect on alpha-glucosidase activity at pH 4.0 and 5.0. The glucose analogues displayed only marginal (-10%) inhibition of alpha-glucosidase activity at pH 5.0. No effect of the analogues was seen at pH 4.0.(ABSTRACT TRUNCATED AT 250 WORDS)
Salehi
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AA
Department of Pharmacology, University of Lund, Sweden.
Lundquist
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I
D000118:Acetylglucosaminidase / Q000378:metabolism; D000135:Acid Phosphatase / Q000378:metabolism; D000818:Animals; D003000:Clonidine / Q000494:pharmacology*; D003847:Deoxyglucose / Q000494:pharmacology*; D004347:Drug Interactions; D005260:Female; D005947:Glucose / Q000494:pharmacology; D005959:Glucosidases / Q000378:metabolism; D066298:In Vitro Techniques; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D008247:Lysosomes / Q000187:drug effects* / Q000201:enzymology; D008356:Mannoheptulose / Q000494:pharmacology*; D051379:Mice
D007328:Insulin; D008356:Mannoheptulose; D003847:Deoxyglucose; D000135:Acid Phosphatase; D005959:Glucosidases; D000118:Acetylglucosaminidase; D005947:Glucose; D003000:Clonidine