Endocrine Abstracts (2008) 16 P215

Metabolic changes induced by glucose infusion in persons with Glu23Lys polymorphism

Thomas Bobbert, Marc Mittag, Knut Mai, Antje Fischer, Ayman Arafat, AFH Pfeiffer & Joachim Spranger

Charité, Berlin, Germany.

The development of diabetes mellitus type 2 (T2DM) is affected by genetic and lifestyle factors. Polymorphisms within the KIR6.2 gene seem to be associated with a higher risk for T2DM. The protein encoded by this gene represents a potassium channel, which plays an essential role in insulin and glucagon secretion by the pancreas.

A hyperglycaemic clamp without insulin was performed over 2 h in 10 healthy persons with the Kir6.2 E23K wild type Glu/Glu, 10 age-, BMI- and sex-matched persons being heterogenous at Kir6.2 E23K (Glu/Lys) and 10 persons with the Lys/Lys genotype. Effects on insulin and glucagon secretion were analysed.

Insulin values were not different, although the maximum peak of the insulin answer was delayed for the Lys/Lys group (Glu/Glu-peak: 2.5 min, Lys/Lys-peak: 5 min). Glucagon was at baseline significantly different between Glu/Glu (39.1±2.9 pg/ml) and Lys/Lys (30.3±1.6) individuals (P=0.015). In addition, Glucagon decreased significantly in the Lys/Lys group after 2 h (85.9±2.3%; P<0.001) and the AUC values for the glucagon time course showed significant lower results (4218±332 vs 3321±194; P=0.035) compared to the Glu/Glu group.

In conclusion we demonstrated in this study for the first time lower glucagon levels in healthy persons with the Glu23Lys variant in the KIR6.2 gene. In addition a stronger reduction in glucagon suppression after i.v. glucose was found. These results in healthy individuals indicate that specifically effects on glucagon secretion might contribute to the development of type 2 diabetes.

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