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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Effect of glucagon on carbohydrate- mediated secretion of glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (7-36 amide) (GLP-1).

BACKGROUND: The insulinotropic hormones, glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (7-36 amide) (GLP-1), regulate insulin secretion to nutrient intake and constitute the endocrine arm of the entero-insular axis. Glucagon has been implicated in the pathophysiology of conditions characterised by abnormal glucose tolerance such as obesity and diabetes mellitus although its effect on the entero-insular axis is not fully understood. Materials and methods We investigated the effect of exogenous glucagon on the entero-insular axis and its relation to gastric emptying in six healthy men aged [mean (+/-S.E.M. )] 23.6 (0.9) years with a body mass index of 24.0 (1.5) kg/m(2). Plasma glucose, GIP, GLP-1, insulin and paracetamol concentrations were measured before and after a 100 g oral carhohydrate load containing 1.5 g of paracetamol for 6 h during intravenous infusion of either glucagon or saline. RESULTS: When compared to the saline infusion, peak and integrated insulin and glucose concentrations were higher (p<0.05) following glucagon infusion. After 60 min paracetamol concentrations were lower (p<0.05) following glucagon infusion. Integrated responses for GIP and GLP-1 were markedly reduced following glucagon infusion. CONCLUSIONS: Exogenous glucagon in addition to its well-documented action of increasing glucose and insulin concentrations and delaying gastric emptying also markedly reduces GIP and GLP-1 secretion. The inhibition of GLP-1 soon after commencement of glucagon infusion supports a direct effect of glucagon on intestinal L-cells. We speculate that the marked inhibition of postprandial GLP-1 secretion by glucagon may be of importance in the pathogenesis of relative insulinopenia in Type 2 diabetes and in the development of reduced satiety in obesity and diabetes.[1]


  1. Effect of glucagon on carbohydrate-mediated secretion of glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (7-36 amide) (GLP-1). Ranganath, L., Schaper, F., Gama, R., Morgan, L., Wright, J., Teale, D., Marks, V. Diabetes Metab. Res. Rev. (1999) [Pubmed]
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