title: Effects of cytochalasin B and D upon insulin release and pancreatic islet cell metabolism.
abstract: Cytochalasin B is known to enhance insulin release evoked by nutrient and non-nutrient secretagogues, including D-glucose, despite inhibiting D-glucose uptake and metabolism in pancreatic islets. In the present study, cytochalasin D, which failed to affect D-glucose uptake and metabolism by isolated islets, also augmented glucose-stimulated insulin release, but unexpectedly to a lesser extent than cytochalasin B. Such was not the case, however, in islets stimulated by non-glucidic nutrients such as 2-ketoisocaproate or the association of L-leucine and L-glutamine. This situation coincided with the fact that cytochalasin B inhibited more severely D-glucose metabolism in non-B, as distinct from B, islet cells and, in the former case, caused a relatively greater inhibition of hexose catabolism at 2.8 mM than at 16.7 mM D-glucose. Nevertheless, even in the presence of forskolin, cytochalasin B was more efficient than cytochalasin D in augmenting glucose-stimulated insulin secretion. Thus, although these data document that non-B islet cells are more sensitive than purified islet B cells to cytochalasin B, at least in terms of inhibition of D-glucose catabolism, such a difference and its possible consequence upon the release of glucagon and other non-insulinic hormones by non-B islet cells do not appear sufficient to account for the greater enhancing action of cytochalasin B, as distinct from cytochalasin D, upon glucose-stimulated insulin output. Likewise, the latter difference does not appear attributable to a greater efficiency of cytochalasin B, as compared to cytochalasin D, upon the mechanical events involved in nutrient-stimulated exocytosis of insulin granules. Hence, the present findings suggest a so-far-unidentified interference of cytochalasin B with the B-cell glucose-sensing device.
authors.affiliation: Laboratory of Experimental Medicine, Brussels Free University, B-1070 Brussels, Belgium.
authors.forename: Hassan
authors.initials: H
authors.lastname: Jijakli
authors.forename: Hai-Xia
authors.initials: HX
authors.lastname: Zhang
authors.forename: Eszter
authors.initials: E
authors.lastname: Dura
authors.forename: Remedios
authors.initials: R
authors.lastname: Ramirez
authors.forename: Abdullah
authors.initials: A
authors.lastname: Sener
authors.forename: Willy J
authors.initials: WJ
authors.lastname: Malaisse
mesh_terms: D019325:3-O-Methylglucose / Q000378:metabolism; D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D002245:Carbon Dioxide / Q000378:metabolism; D005576:Colforsin / Q000494:pharmacology; D003571:Cytochalasin B / Q000494:pharmacology*; D015638:Cytochalasin D / Q000494:pharmacology*; D005947:Glucose / Q000378:metabolism; D005973:Glutamine / Q000494:pharmacology; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects* / Q000378:metabolism*; D007651:Keto Acids / Q000494:pharmacology; D007930:Leucine / Q000494:pharmacology; D011868:Radioisotopes; D051381:Rats; D014867:Water / Q000378:metabolism
chemical_list: D000596:Amino Acids; D007328:Insulin; D007651:Keto Acids; D011868:Radioisotopes; D014867:Water; D005973:Glutamine; D002245:Carbon Dioxide; D019325:3-O-Methylglucose; D005576:Colforsin; D015638:Cytochalasin D; D003571:Cytochalasin B; C013082:alpha-ketoisocaproic acid; D007930:Leucine; D005947:Glucose