GIP does not potentiate the antidiabetic effects of GLP-1 in hyperglycemic patients with type 2 diabetes
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GIP does not potentiate the antidiabetic effects of GLP-1 in hyperglycemic patients with type 2 diabetes. / Mentis, Nikolaos; Vardarli, Irfan; Köthe, Lars D; Holst, Jens Juul; Deacon, Carolyn F; Theodorakis, Michael; Meier, Juris J; Nauck, Michael A.
In: Diabetes, Vol. 60, No. 4, 2011, p. 1270-1276.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - GIP does not potentiate the antidiabetic effects of GLP-1 in hyperglycemic patients with type 2 diabetes
AU - Mentis, Nikolaos
AU - Vardarli, Irfan
AU - Köthe, Lars D
AU - Holst, Jens Juul
AU - Deacon, Carolyn F
AU - Theodorakis, Michael
AU - Meier, Juris J
AU - Nauck, Michael A
PY - 2011
Y1 - 2011
N2 - OBJECTIVE The incretin glucagon-like peptide 1 (GLP-1) exerts insulinotropic activity in type 2 diabetic patients, whereas glucose-dependent insulinotropic polypeptide (GIP) no longer does. We studied whether GIP can alter the insulinotropic or glucagonostatic activity of GLP-1 in type 2 diabetic patients. RESEARCH DESIGN AND METHODS Twelve patients with type 2 diabetes (nine men and three women; 61 ± 10 years; BMI 30.0 ± 3.7 kg/m2; HbA1c 7.3 ± 1.5%) were studied. In randomized order, intravenous infusions of GLP-1(7-36)-amide (1.2 pmol · kg-1 · min-1), GIP (4 pmol · kg-1 · min-1), GLP-1 plus GIP, and placebo were administered over 360 min after an overnight fast (=1 day wash-out period between experiments). Capillary blood glucose, plasma insulin, C-peptide, glucagon, GIP, GLP-1, and free fatty acids (FFA) were determined. RESULTS Exogenous GLP-1 alone reduced glycemia from 10.3 to 5.1 ± 0.2 mmol/L. Insulin secretion was stimulated (insulin, C-peptide, P < 0.0001), and glucagon was suppressed (P = 0.009). With GIP alone, glucose was lowered slightly (P = 0.0021); insulin and C-peptide were stimulated to a lesser degree than with GLP-1 (P < 0.001). Adding GIP to GLP-1 did not further enhance the insulinotropic activity of GLP-1 (insulin, P = 0.90; C-peptide, P = 0.85). Rather, the suppression of glucagon elicited by GLP-1 was antagonized by the addition of GIP (P = 0.008). FFA were suppressed by GLP-1 (P < 0.0001) and hardly affected by GIP (P = 0.07). CONCLUSIONS GIP is unable to further amplify the insulinotropic and glucose-lowering effects of GLP-1 in type 2 diabetes. Rather, the suppression of glucagon by GLP-1 is antagonized by GIP.
AB - OBJECTIVE The incretin glucagon-like peptide 1 (GLP-1) exerts insulinotropic activity in type 2 diabetic patients, whereas glucose-dependent insulinotropic polypeptide (GIP) no longer does. We studied whether GIP can alter the insulinotropic or glucagonostatic activity of GLP-1 in type 2 diabetic patients. RESEARCH DESIGN AND METHODS Twelve patients with type 2 diabetes (nine men and three women; 61 ± 10 years; BMI 30.0 ± 3.7 kg/m2; HbA1c 7.3 ± 1.5%) were studied. In randomized order, intravenous infusions of GLP-1(7-36)-amide (1.2 pmol · kg-1 · min-1), GIP (4 pmol · kg-1 · min-1), GLP-1 plus GIP, and placebo were administered over 360 min after an overnight fast (=1 day wash-out period between experiments). Capillary blood glucose, plasma insulin, C-peptide, glucagon, GIP, GLP-1, and free fatty acids (FFA) were determined. RESULTS Exogenous GLP-1 alone reduced glycemia from 10.3 to 5.1 ± 0.2 mmol/L. Insulin secretion was stimulated (insulin, C-peptide, P < 0.0001), and glucagon was suppressed (P = 0.009). With GIP alone, glucose was lowered slightly (P = 0.0021); insulin and C-peptide were stimulated to a lesser degree than with GLP-1 (P < 0.001). Adding GIP to GLP-1 did not further enhance the insulinotropic activity of GLP-1 (insulin, P = 0.90; C-peptide, P = 0.85). Rather, the suppression of glucagon elicited by GLP-1 was antagonized by the addition of GIP (P = 0.008). FFA were suppressed by GLP-1 (P < 0.0001) and hardly affected by GIP (P = 0.07). CONCLUSIONS GIP is unable to further amplify the insulinotropic and glucose-lowering effects of GLP-1 in type 2 diabetes. Rather, the suppression of glucagon by GLP-1 is antagonized by GIP.
KW - Adult
KW - Aged
KW - Diabetes Mellitus, Type 2
KW - Drug Interactions
KW - Female
KW - Gastric Inhibitory Polypeptide
KW - Glucagon-Like Peptide 1
KW - Humans
KW - Hyperglycemia
KW - Hypoglycemic Agents
KW - Incretins
KW - Male
KW - Middle Aged
U2 - 10.2337/db10-1332
DO - 10.2337/db10-1332
M3 - Journal article
C2 - 21330636
VL - 60
SP - 1270
EP - 1276
JO - Diabetes
JF - Diabetes
SN - 0012-1797
IS - 4
ER -
ID: 33725546