Abstract
| Originalsprog | Engelsk |
|---|---|
| Tidsskrift | Journal of Clinical Endocrinology and Metabolism |
| Vol/bind | 94 |
| Udgave nummer | 2 |
| Sider (fra-til) | 603-8 |
| Antal sider | 6 |
| ISSN | 0021-972X |
| DOI | |
| Status | Udgivet - 2008 |
Bibliografisk note
Keywords: Aged; Blood Glucose; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Female; Gastric Inhibitory Polypeptide; Glucagon; Glucose Clamp Technique; Humans; Hypoglycemic Agents; Infusion Pumps; Insulin; Insulin Resistance; Ion Channel Gating; KATP Channels; Male; Middle Aged; Sulfonylurea CompoundsAdgang til dokumentet
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KATP channel closure ameliorates the impaired insulinotropic effect of glucose-dependent insulinotropic polypeptide in patients with type 2 diabetes. / Aaboe, Kasper; Knop, Filip Krag; Vilsboll, Tina; Vølund, Aage; Simonsen, Ulf; Deacon, Carolyn F.; Madsbad, Sten; Holst, Jens Juul; Krarup, Thure.
I: Journal of Clinical Endocrinology and Metabolism, Bind 94, Nr. 2, 2008, s. 603-8.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review
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TY - JOUR
T1 - KATP channel closure ameliorates the impaired insulinotropic effect of glucose-dependent insulinotropic polypeptide in patients with type 2 diabetes
AU - Aaboe, Kasper
AU - Knop, Filip Krag
AU - Vilsboll, Tina
AU - Vølund, Aage
AU - Simonsen, Ulf
AU - Deacon, Carolyn F.
AU - Madsbad, Sten
AU - Holst, Jens Juul
AU - Krarup, Thure
N1 - Keywords: Aged; Blood Glucose; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Female; Gastric Inhibitory Polypeptide; Glucagon; Glucose Clamp Technique; Humans; Hypoglycemic Agents; Infusion Pumps; Insulin; Insulin Resistance; Ion Channel Gating; KATP Channels; Male; Middle Aged; Sulfonylurea Compounds
PY - 2008
Y1 - 2008
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.
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.
U2 - 10.1210/jc.2008-1731
DO - 10.1210/jc.2008-1731
M3 - Journal article
C2 - 19050053
VL - 94
SP - 603
EP - 608
JO - Journal of Clinical Endocrinology and Metabolism
JF - Journal of Clinical Endocrinology and Metabolism
SN - 0021-972X
IS - 2
ER -