Therapeutical concentrations of tolbutamide, glibenclamide, gliclazide and gliquidone at different glucose levels: in vitro effects on pancreatic A- and B-cell function

Gregorio, F. Di; Ambrosi, F; Cristallini, S.; Pedetti, M.; Filipponi, P; Santeusanio, Fausto

doi:10.1016/0168-8227(92)90146-i

Cited by 47 publications

(22 citation statements)

References 28 publications

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“…In contrast, in our previous study, we demonstrated only nonsignificant stimulation of arginine-induced insulin release by glibenclamide (1). This current finding is consistent with previous findings that gliclazide is more potent in stimulating the first phase of insulin release from isolated perfused pancreas (35).…”

Section: Discussionsupporting

confidence: 92%

Gliclazide Directly Inhibits Arginine-Induced Glucagon Release

et al. 2002

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Arginine-stimulated insulin and somatostatin release is enhanced by the sulfonylurea gliclazide. In contrast, gliclazide inhibits the glucagon response. The aim of the present study was to investigate whether this inhibition of glucagon release was mediated by a direct suppressive effect of gliclazide or was secondary to the paracrine effect of released somatostatin. To eliminate the paracrine effects of somatostatin, we first perfused isolated rat pancreata with a medium supplemented with 23% of the standard calcium content. Second, we perifused isolated rat islets with a novel and highly specific antagonist of type 2 somatostatin receptor, DC-41-33 (2 mol/l), which fully antagonizes the suppressive somatostatin effect on rat A cells. Gliclazide (30 mol/l) inhibited glucagon release by 54% in the perfusion experiments, whereas the somatostatin response was nearly abolished. In islet perifusions with DC-41-33, arginineinduced glucagon release was inhibited by 66%. We therefore concluded that gliclazide inhibits glucagon release by a direct action on the pancreatic A cell. Diabetes 51 (Suppl. 3):S381-S384, 2002

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Section: Discussionsupporting

confidence: 92%

Gliclazide Directly Inhibits Arginine-Induced Glucagon Release

et al. 2002

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“…While it is well established that hyperglycemia suppresses glucagon secretion strongly, the effect of sulfonylurea on glucagon secretion is controversial and reported to be unaffected (17), stimulated (38), inhibited (39), and influenced differently depending on the prevailing glucose and drug concentration and presence of paracrine effectors (38,40,41). We observed that during infusion with tolbutamide alone, glucagon secretion did not rise in the presence of 3 mmol/l glucose.…”

Section: Discussionmentioning

confidence: 54%

“…By applying the K ATP channel-inhibitor tolbutamide in a dose of 185 mol/l (50 mg/l), which is within the therapeutic range in humans, we bypassed the precondition of elevated glucose levels, and showed GLP-1-induced insulin secretion at a glucose concentration of 3 mmol/l (17,27). These results are in line with clinical trials, in which the incidence of mild to moderate hypoglycemia was greatly increased in diabetic patients receiving combination therapy of the GLP-1 mimetic exendin-4 and sulfonylurea (8 -11).…”

Section: Discussionmentioning

confidence: 99%

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Sulfonylurea Compounds Uncouple the Glucose Dependence of the Insulinotropic Effect of Glucagon-Like Peptide 1

2007

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“…However, when plasma glucose concentrations were allowed to fall, as in the lower panel of Figure 1 in the current study, there was absolutely no discernible change in glucagon concentrations [19]. Furthermore, it also appears from resuits of recent studies that sulfonylureas do not influence alpha-cell function, either directly or indirectly by a paracrine effect via insulin suppression [21]. While glucagon concentrations were not measured in the present study, it is unlikely that such a small dose of tolbutamide could have had any significant impact.…”

Section: Discussionmentioning

confidence: 71%

Evidence that insulin can directly inhibit hepatic glucose production

et al. 1997

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SummaryIn order to evaluate the role of portal insulin in the modulation of hepatic glucose production (HGP), measurements of plasma glucose and insulin concentrations and both HGP and peripheral glucose disappearance rates were made following an infusion of a dose of tolbutamide (0.74 mgm -2. min -1) in healthy volunteers that does not result in an increase in peripheral vein insulin concentrations or metabolic clearance rate of glucose. The results showed that the infusion of such a dose of tolbutamide was associated with a significant and rapid decline in both HGP (from 9.0 + 0.5 to 7.7 + 0.5~tmol.kg -1.min -1 or A= -13.8+4.5%; p< 0.001 compared to saline) and plasma glucose concentration (from 5.1+ 0.2 to 4.4+ 0.1mmol/l or A = -13.0 + 2.1%; p < 0.01 compared to saline). Since neither HGP nor fasting glucose fell when tolbutamide-stimulated insulin secretion was inhibited by the concurrent administration of somatostatin, it indicated that tolbutamide by itself, does not directly inhibit HGP. Finally, HGP fell by 26.3 + 6.0 % at 10 min after a dose of tolbutamide that elevated both peripheral and portal insulin concentrations, at a time when HGP had barely increased (A = + 6.9 + 5.3 %). The difference in the magnitude of the two responses was statistically significant (p < 0.03), providing further support for the view that insulin can directly inhibit HGP, independent of any change in flow of substrates from periphery to liver. [Diabetologia (1997[Diabetologia ( ) 40: 1300[Diabetologia ( -1306 Keywotds Liver, insulin, portal system, C-peptide, tolbutamide.Evidence has been published showing that hepatic glucose production (HGP) is decreased following the infusion of either insulin or sulfonylurea compounds [1][2][3][4], and this is generally assumed to be due to a direct effect of insulin on the liver. However, the results of two recent studies in dogs [5,6] of insulin, suggesting that the ability of insulin to inhibit HGP may be mediated through its peripheral action on substrate flow to the liver. Although we think it reasonable that insulin can inhibit HGP by decreasing substrate flow to the liver, the experiments to be presented were initiated to see whether insulin can also inhibit HGP directly. In order to accomplish this task non-invasively, we measured HGP, in normal subjects, in response to a continuous infusion of tolbutamide that would not significantly increase peripheral insulin concentrations and compared it to a saline) infusion. Under these conditions, HGP should have been similar in both studies if HGP was only modulated by the peripheral inhibition of substrate flow. Since HGP was significantly lower following tolbutamide, the data are consistent with the hypothesis that insulin can directly inhibit HGE

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Therapeutical concentrations of tolbutamide, glibenclamide, gliclazide and gliquidone at different glucose levels: in vitro effects on pancreatic A- and B-cell function

Cited by 47 publications

References 28 publications

Gliclazide Directly Inhibits Arginine-Induced Glucagon Release

Gliclazide Directly Inhibits Arginine-Induced Glucagon Release

Sulfonylurea Compounds Uncouple the Glucose Dependence of the Insulinotropic Effect of Glucagon-Like Peptide 1

Evidence that insulin can directly inhibit hepatic glucose production

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