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GLP-1 Restores Altered Insulin and Glucagon Secretion in Posttransplantation Diabetes
Oleh:
Halden, Thea A. S.
;
Egeland, Erlend J.
;
Asberg, Anders
;
Hartmann, Anders
;
Midtvedt, Karsten
Jenis:
Article from Journal - ilmiah internasional
Dalam koleksi:
Diabetes Care vol. 39 no. 04 (Apr. 2016)
,
page 617-624.
Topik:
Posttransplantation Diabetes
;
PTDM
Ketersediaan
Perpustakaan FK
Nomor Panggil:
D05.K
Non-tandon:
1 (dapat dipinjam: 0)
Tandon:
tidak ada
Lihat Detail Induk
Isi artikel
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.
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