TY - JOUR
T1 - K-ATP Channel Closure Ameliorates the Impaired Insulinotropic Effect of Glucose-Dependent Insulinotropic Polypeptide in Patients with Type 2 Diabetes
AU - Aaboe, K.
AU - Knop, K.
AU - Vilsboll, T.
AU - Volund, A.
AU - Simonsen, U.
AU - Deacon, C.F.
AU - Madsbad, S.
AU - Holst, J.J.
AU - Krarup, T.
N1 - JFEB
PY - 2009
Y1 - 2009
N2 - Objective: The reduced incretin effect in subjects with type 2 diabetes is accompanied by a severely impaired insulinotropic effect of the incretin hormone glucose-dependent insulinotropic polypeptide (GIP). The K-ATP channels of the beta-cell appear to be essential for the function of GIP in mice, and mutations in the gene encoding these channels have been linked to the development of type 2 diabetes. With this study we therefore aimed at clarifying the role of K-ATP channel malfunction in the impaired function of GIP. Research Design and Methods: We examined 12 subjects with type 2 diabetes using a 2-h (15 mM) hyperglycemic clamp on 4 separate days with concomitant infusion of one of the following: GIP; GIP + 10 mg sulfonylurea (SU, glipizide) taken orally 1 h before the clamp; saline + 10 mg SU; or saline alone. Blood was sampled to measure plasma concentrations of glucose, intact GIP, insulin, C-peptide, and glucagon. Results: Compared to the results of GIP alone, SU alone, or those results added together, coadministration of GIP and SU resulted in a more-than-additive increase in the peripheral insulin (P = 0.002) and C-peptide (P = 0.028) responses and furthermore, a more-than-additive increase in total (P = 0.01), early (P = 0.02), and late-phase (P = 0.02) insulin secretion. Conclusion: We have demonstrated that inhibiting the K-ATP channels of the diabetic beta-cell acutely using SU significantly increases both the peripheral insulin response to GIP and GIP-induced insulin secretion, indicating an ameliorated insulinotropic effect of GIP. (J Clin Endocrinol Metab 94: 603-608, 2009)
Udgivelsesdato: 2009
AB - Objective: The reduced incretin effect in subjects with type 2 diabetes is accompanied by a severely impaired insulinotropic effect of the incretin hormone glucose-dependent insulinotropic polypeptide (GIP). The K-ATP channels of the beta-cell appear to be essential for the function of GIP in mice, and mutations in the gene encoding these channels have been linked to the development of type 2 diabetes. With this study we therefore aimed at clarifying the role of K-ATP channel malfunction in the impaired function of GIP. Research Design and Methods: We examined 12 subjects with type 2 diabetes using a 2-h (15 mM) hyperglycemic clamp on 4 separate days with concomitant infusion of one of the following: GIP; GIP + 10 mg sulfonylurea (SU, glipizide) taken orally 1 h before the clamp; saline + 10 mg SU; or saline alone. Blood was sampled to measure plasma concentrations of glucose, intact GIP, insulin, C-peptide, and glucagon. Results: Compared to the results of GIP alone, SU alone, or those results added together, coadministration of GIP and SU resulted in a more-than-additive increase in the peripheral insulin (P = 0.002) and C-peptide (P = 0.028) responses and furthermore, a more-than-additive increase in total (P = 0.01), early (P = 0.02), and late-phase (P = 0.02) insulin secretion. Conclusion: We have demonstrated that inhibiting the K-ATP channels of the diabetic beta-cell acutely using SU significantly increases both the peripheral insulin response to GIP and GIP-induced insulin secretion, indicating an ameliorated insulinotropic effect of GIP. (J Clin Endocrinol Metab 94: 603-608, 2009)
Udgivelsesdato: 2009
M3 - Journal article
SN - 0021-972X
VL - 94
SP - 603
EP - 608
JO - Journal of Clinical Endocrinology and Metabolism
JF - Journal of Clinical Endocrinology and Metabolism
IS - 2
ER -
