GLP-1 Restores Altered Insulin and Glucagon Secretion in Posttransplantation Diabetes
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GLP-1 Restores Altered Insulin and Glucagon Secretion in Posttransplantation Diabetes. / Halden, Thea A S; Egeland, Erlend J; Åsberg, Anders; Hartmann, Anders; Midtvedt, Karsten; Khiabani, Hassan Z; Holst, Jens J; Knop, Filip K; Hornum, Mads; Feldt-Rasmussen, Bo; Jenssen, Trond.
In: Diabetes Care, Vol. 39, 23.02.2016, p. 617-24.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - GLP-1 Restores Altered Insulin and Glucagon Secretion in Posttransplantation Diabetes
AU - Halden, Thea A S
AU - Egeland, Erlend J
AU - Åsberg, Anders
AU - Hartmann, Anders
AU - Midtvedt, Karsten
AU - Khiabani, Hassan Z
AU - Holst, Jens J
AU - Knop, Filip K
AU - Hornum, Mads
AU - Feldt-Rasmussen, Bo
AU - Jenssen, Trond
N1 - © 2016 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.
PY - 2016/2/23
Y1 - 2016/2/23
N2 - OBJECTIVE: Development of posttransplantation diabetes (PTDM) is characterized by reduced insulin secretion and sensitivity. We aimed to investigate whether hyperglucagonemia could play a role in PTDM and to examine the insulinotropic and glucagonostatic effects of the incretin hormone glucagon-like peptide 1 (GLP-1) during fasting and hyperglycemic conditions, respectively.RESEARCH DESIGN AND METHODS: Renal transplant recipients with (n = 12) and without (n = 12) PTDM underwent two separate experimental days with 3-h intravenous infusions of GLP-1 (0.8 pmol/kg/min) and saline, respectively. After 1 h of infusion, a 2-h hyperglycemic clamp (fasting plasma glucose + 5 mmol/L) was established. Five grams of arginine was given as an intravenous bolus 10 min before termination of the clamp.RESULTS: Fasting concentrations of glucagon (P = 0.92) and insulin (P = 0.23) were similar between the groups. In PTDM patients, glucose-induced glucagon suppression was significantly less pronounced (maximal suppression from baseline: 43 ± 12 vs. 65 ± 12%, P < 0.001), while first- and second-phase insulin secretion were significantly lower. The PTDM group also exhibited a significantly lower insulin response to arginine (P = 0.01) but similar glucagon and proinsulin responses compared with control subjects. In the preclamp phase, GLP-1 lowered fasting plasma glucose to the same extent in both groups but reduced glucagon only in PTDM patients. During hyperglycemic clamp, GLP-1 reduced glucagon concentrations and increased first- and second-phase insulin secretion in both groups.CONCLUSIONS: PTDM is characterized by reduced glucose-induced insulin secretion and attenuated glucagon suppression during a hyperglycemic clamp. Similar to the case in type 2 diabetes, GLP-1 infusion seems to improve (insulin) or even normalize (glucagon) these pathophysiological defects.
AB - OBJECTIVE: Development of posttransplantation diabetes (PTDM) is characterized by reduced insulin secretion and sensitivity. We aimed to investigate whether hyperglucagonemia could play a role in PTDM and to examine the insulinotropic and glucagonostatic effects of the incretin hormone glucagon-like peptide 1 (GLP-1) during fasting and hyperglycemic conditions, respectively.RESEARCH DESIGN AND METHODS: Renal transplant recipients with (n = 12) and without (n = 12) PTDM underwent two separate experimental days with 3-h intravenous infusions of GLP-1 (0.8 pmol/kg/min) and saline, respectively. After 1 h of infusion, a 2-h hyperglycemic clamp (fasting plasma glucose + 5 mmol/L) was established. Five grams of arginine was given as an intravenous bolus 10 min before termination of the clamp.RESULTS: Fasting concentrations of glucagon (P = 0.92) and insulin (P = 0.23) were similar between the groups. In PTDM patients, glucose-induced glucagon suppression was significantly less pronounced (maximal suppression from baseline: 43 ± 12 vs. 65 ± 12%, P < 0.001), while first- and second-phase insulin secretion were significantly lower. The PTDM group also exhibited a significantly lower insulin response to arginine (P = 0.01) but similar glucagon and proinsulin responses compared with control subjects. In the preclamp phase, GLP-1 lowered fasting plasma glucose to the same extent in both groups but reduced glucagon only in PTDM patients. During hyperglycemic clamp, GLP-1 reduced glucagon concentrations and increased first- and second-phase insulin secretion in both groups.CONCLUSIONS: PTDM is characterized by reduced glucose-induced insulin secretion and attenuated glucagon suppression during a hyperglycemic clamp. Similar to the case in type 2 diabetes, GLP-1 infusion seems to improve (insulin) or even normalize (glucagon) these pathophysiological defects.
U2 - 10.2337/dc15-2383
DO - 10.2337/dc15-2383
M3 - Journal article
C2 - 26908914
VL - 39
SP - 617
EP - 624
JO - Diabetes Care
JF - Diabetes Care
SN - 0149-5992
ER -
ID: 159744153