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102. Secretion of incretin hormones and the insulinotropic effect of gastric inhibitory polypeptide in women with a history of gestational diabetes

Author

Meier, J J, Gallwitz, B, Askenas, M, Vollmer, K, Deacon, C F, Holst, Jens Juul, Schmidt, W E, Nauck, M A, Meier, J J, Gallwitz, B, Askenas, M, Vollmer, K, Deacon, C F, Holst, Jens Juul, Schmidt, W E, and Nauck, M A

Abstract

AIMS/HYPOTHESIS: The insulinotropic effect of gastric inhibitory polypeptide (GIP) is reduced in patients with type 2 diabetes and around 50% of their first-degree relatives under hyperglycaemic conditions. It is unknown whether this is a result of a specific defect in GIP action or of a general reduction in beta cell function. Moreover, impaired secretion of glucagon-like peptide 1 (GLP-1) has been described in patients with type 2 diabetes. Therefore, we studied the insulinotropic effect of GIP in women with previous gestational diabetes (pGDM) under euglycaemic fasting conditions and during a hyperglycaemic clamp experiment. The secretion of GIP and GLP-1 was assessed following oral glucose ingestion.MATERIALS AND METHODS: On separate occasions we performed an OGTT and administered an i.v. bolus of 20 pmol GIP/kg body weight in 20 women with pGDM and 20 control women. An additional hyperglycaemic clamp experiment (140 mg/dl [7.8 mmol/l] over 120 min) with i.v. infusion of GIP (2 pmol kg(-1) min(-1); 30-90 min) was performed in 14 women in each group. Capillary and venous blood samples were drawn for the measurement of glucose (glucose oxidase), insulin, C-peptide, GIP and GLP-1 (specific immunoassays). Indices of insulin sensitivity and beta cell function were calculated. Statistical analyses were carried out using repeated measures ANOVA.RESULTS: Following oral glucose ingestion, plasma glucose, insulin and C-peptide concentrations increased to higher levels in the women with pGDM than in the control women (p<0.05). The women with pGDM were characterised by a higher degree of insulin resistance than the control women (p=0.007 for the Matsuda index), but showed no overt defects in glucose-stimulated insulin secretion (p=0.40 for the insulinogenic index following i.v. glucose). The secretion of GLP-1 and GIP was not different between the groups (p=0.87 and p=0.57, respectively). The insulin secretory response to GIP administration was similar i

Published
2005

104. Behandlung des Diabetes mellitus Typ 2*

Author

Matthaei, S., primary, Bierwirth, R., additional, Fritsche, A., additional, Gallwitz, B., additional, Häring, H.-U., additional, Joost, H.-G., additional, Kellerer, M., additional, Kloos, C., additional, Kunt, T., additional, Nauck, M., additional, Schernthaner, G., additional, Siegel, E., additional, and Thienel, F., additional

Published
2012
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116. Behandlung des Diabetes mellitus Typ 2

Author

Matthaei, S, primary, Bierwirth, R, additional, Fritsche, A, additional, Gallwitz, B, additional, Häring, H-U, additional, Joost, H-G, additional, Kellerer, M, additional, Kloos, C, additional, Kunt, T, additional, Nauck, M, additional, Schernthaner, G, additional, Siegel, E, additional, and Thienel, F, additional

Published
2011
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121. Gastric inhibitory polypeptide (GIP) dose-dependently stimulates glucagon secretion in healthy human subjects at euglycaemia

Author

Meier, J J, Gallwitz, B, Siepmann, N, Holst, Jens Juul, Deacon, C F, Schmidt, W E, Nauck, M A, Meier, J J, Gallwitz, B, Siepmann, N, Holst, Jens Juul, Deacon, C F, Schmidt, W E, and Nauck, M A

Abstract

AIMS/HYPOTHESIS: In the isolated perfused pancreas, gastric inhibitory polypeptide (GIP) has been shown to enhance glucagon secretion at basal glucose concentrations, but in healthy humans no glucagonotropic effect of GIP has yet been reported. Therefore, we studied the effect of GIP on glucagon secretion under normoglycaemic conditions.METHODS: Ten healthy subjects (9 men, 1 woman; age 33+/-11; BMI 26.8+/-2.2 kg/m(2)) received three different doses of intravenous GIP (7, 20, and 60 pmol/kg body weight) and placebo. Venous blood samples were drawn over 30 min for glucagon and GIP concentrations (specific radioimmunoassays). In addition, 31 healthy subjects (16 men, 15 women; 42+/-11 years; BMI 24.4+/-2.7 kg/m(2)) were studied with 20 pmol GIP/kg. Statistics were done with RM-ANOVA and Duncan's post hoc tests.RESULTS: Gastric inhibitory polypeptide dose-dependently stimulated glucagon secretion ( p=0.019) with a maximal increment after 10 min. Incremental glucagon concentrations (Delta(10-0 min)) were 0.1+/-0.7, 1.4+/-0.5, 2.4+/-0.5, and 3.4+/-0.8 pmol/l (for placebo and for 7, 20, and 60 pmol GIP/kg, respectively; p=0.017). After the injection of 20 pmol GIP/kg b.w. in 31 healthy subjects, glucagon concentrations increased over the baseline from 7.5+/-0.5 to 9.3+/-0.7 pmol/l ( p=0.0082).CONCLUSIONS/INTERPRETATION: Glucagon secretion is dose-dependently stimulated by GIP at basal glucose concentrations. The absence of a glucagonotropic GIP effect in previous studies could be due to the hyperglycaemic conditions used in these experiments. Our results underline differences between GIP and the glucagonostatic incretin GLP-1.

Published
2003

127. Behandlung des Diabetes mellitus Typ 2

Author

Matthaei, S., primary, Bierwirth, R., additional, Fritsche, A., additional, Gallwitz, B., additional, Häring, H.-U., additional, Joost, H.-G., additional, Kellerer, M., additional, Kloos, C., additional, Kunt, T., additional, Nauck, M., additional, Schernthaner, G., additional, Siegel, E., additional, and Thienel, F., additional

Published
2010
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129. Association of Somatostatin Receptor 2 Immunohistochemical Expression with [111In]-DTPA Octreotide Scintigraphy and [68Ga]-DOTATOC PET/CT in Neuroendocrine Tumors

Author

Müssig, K., primary, Öksüz, M. Ö., additional, Dudziak, K., additional, Ueberberg, B., additional, Wehrmann, M., additional, Horger, M., additional, Schulz, S., additional, Häring, H.U., additional, Pfannenberg, C., additional, Bares, R., additional, Gallwitz, B., additional, and Petersenn, S., additional

Published
2010
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131. O84 Effet de l’exénatide et du glimeripide sur le poids, la composition corporelle et la distribution de la masse grasse. Résultats d’une étude prospective, contrôlée et randomisée sur 9 mois

Author

Kazda, C.M., primary, Schernthaner, G., additional, Dotta, F., additional, Rose, L., additional, Guerci, B., additional, Cueille, C., additional, Salaün-Martin, C., additional, Kraus, P., additional, Nicolay, C., additional, and Gallwitz, B., additional

Published
2010
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137. Medical Antihyperglycaemic Treatment of Type 2 Diabetes Mellitus

Author

Matthaei, S., primary, Bierwirth, R., additional, Fritsche, A., additional, Gallwitz, B., additional, Häring, H.-U., additional, Joost, H.-G., additional, Kellerer, M., additional, Kloos, Ch., additional, Kunt, T., additional, Nauck, M., additional, Schernthaner, G., additional, Siegel, E., additional, and Thienel, F., additional

Published
2009
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138. Behandlung des Diabetes mellitus Typ 2

Author

Matthaei, S., primary, Bierwirth, R., additional, Fritsche, A., additional, Gallwitz, B., additional, Häring, H.-U., additional, Joost, H.-G., additional, Kellerer, M., additional, Kloos, C., additional, Kunt, T., additional, Nauck, M., additional, Schernthaner, G., additional, Siegel, E., additional, and Thienel, F., additional

Published
2009
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143. Medikamentöse antihyperglykämische Therapie des Diabetes mellitus Typ 2

Author

Matthaei, S., primary, Bierwirth, R., additional, Fritsche, A., additional, Gallwitz, B., additional, Häring, H.-U., additional, Joost, H.-G., additional, Kellerer, M., additional, Kloos, C., additional, Kunt, T., additional, Nauck, M., additional, Schernthaner, G., additional, Siegel, E., additional, and Thienel, F., additional

Published
2009
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