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Extra‐pancreatic action of glibenclamide in man: reduction in vitro of the inhibitory effect of glucagon and epinephrine on the hepatic key glycolytic enzymes phosphofructokinase (PFK) and pyruvate kinase (PK)
Author(s) -
BELFIORE F.,
RABUAZZO AGATA M.,
IANNELLO SILVIA,
CAMPIONE ROSA,
CASTORINA S.,
URZI F.
Publication year - 1989
Publication title -
european journal of clinical investigation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.164
H-Index - 107
eISSN - 1365-2362
pISSN - 0014-2972
DOI - 10.1111/j.1365-2362.1989.tb00243.x
Subject(s) - glibenclamide , phosphofructokinase , glucagon , endocrinology , medicine , pyruvate kinase , epinephrine , gluconeogenesis , glycolysis , chemistry , insulin , biology , metabolism , diabetes mellitus
. Human liver slices (surgery biopsies) were preincubated with glucagon or epinephrine for 10 min at 37°C in Krebs‐Henseleit solution at pH 7.4, in the absence or presence of glibenclamide, and then homogenized and assayed for phosphofructokinase (PFK) and pyruvate kinase (PK) activity at subsaturating, near physiological, substrate concentrations (suitable for detecting regulatory effects). Preincubation with 10 μM glucagon ( n = 7) or 10 μM epinephrine ( n = 7) resulted in a reduction of PFK activity of 25% ( P < 0.02) and 29% ( p < 0.05), respectively. Addition of 2 μM glibenclamide in the preincubation mixture reduced the inhibitory effect of glucagon by 99% ( P < 0.05) and that of epinephrine by 70% ( p < 0.01). Likewise, 10 μM glucagon ( n = 6) or 10 μM epinephrine ( n = 4) reduced PK activity by 40% ( P < 0.01) and 46% ( P < 0.01), respectively. Addition of 2 μM glibenclamide significantly reduced the inhibitory effect of glucagon by 77% ( P < 0.05) and that of epinephrine by 33% ( P < 0.05). In the absence of the hormones, glibenclamide was without effect. Thus, glibenclamide opposes the inhibitory effect of glucagon and epinephrine on two key hepatic glycolytic enzymes. Since the inhibition of key glycolytic enzymes favours gluconeogenesis, the observed action of glibenclamide, if it occurs also in vivo , might reduce the glucagon‐ and epinephrine‐stimulated gluconeogenesis, and could be regarded as an insulin‐like action.