Abstract | AIM: METHODS: RESULTS: 4H2BH alone had no significant effect on cAMP production or insulin secretion from BRIN-BD11 cells. However, 4H2BH significantly inhibited GIP-mediated cAMP production and insulin secretion in vitro. 4H2BH also suppressed (p < 0.05 to p < 0.001) glucagon-induced elevations of cAMP generation and insulin secretion in BRIN-BD11 cells. However, 4H2BH had no effect on glucagon-like peptide-1 (GLP-1) mediated insulinotropic actions. Administration of 4H2BH to mice in combination with glucose and GIP significantly annulled the glucose-lowering actions of GIP. In agreement with this, 4H2BH completely annulled GIP-mediated insulin secretion. Combined injection of 4H2BH with glucagon also partially (p < 0.05 to p < 0.001) impaired glucagon-induced elevations in blood glucose and plasma insulin. 4H2BH had no effect on blood glucose or insulin levels when administered alone. CONCLUSION: These results indicate that 4H2BH has a dual effect of inhibiting GIP and glucagon-mediated biological actions. Given that hyperglucagonaemia is also a cardinal feature of type 2 diabetes, 4H2BH and related low molecular weight compounds appear worthy of further evaluation for therapeutic potential in obesity diabetes.
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Authors | Z J Franklin, B McDonnell, I A Montgomery, P R Flatt, N Irwin |
Journal | Diabetes, obesity & metabolism
(Diabetes Obes Metab)
Vol. 13
Issue 8
Pg. 742-9
(Aug 2011)
ISSN: 1463-1326 [Electronic] England |
PMID | 21418501
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | © 2011 Blackwell Publishing Ltd. |
Chemical References |
- 4-hydroxybenzoic acid 2-bromobenzylidene hydrazide
- Adipokines
- Benzene Derivatives
- Hydrocarbons, Brominated
- Parabens
- Receptors, Gastrointestinal Hormone
- Gastric Inhibitory Polypeptide
- Glucagon
- gastric inhibitory polypeptide receptor
- 4-hydroxybenzoic acid
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Topics |
- Adipokines
- Animals
- Benzene Derivatives
(pharmacology)
- Gastric Inhibitory Polypeptide
(administration & dosage, pharmacology)
- Glucagon
(administration & dosage, pharmacology)
- Hydrocarbons, Brominated
(pharmacology)
- Insulin Resistance
- Male
- Mice
- Obesity
(drug therapy)
- Parabens
(metabolism, pharmacology)
- Receptors, Gastrointestinal Hormone
(metabolism)
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