Niels Jessen

Unacylated Ghrelin does not Acutely Affect Substrate Metabolism or Insulin Sensitivity in Men with Type 2 Diabetes

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Objective: Unacylated ghrelin (UAG) is suggested to improve insulin sensitivity with a therapeutic potential. We therefore tested the effects of intravenous UAG infusion on glucose and lipid metabolism, insulin sensitivity, and energy expenditure in men with type 2 diabetes (T2DM).

Design: A randomized double blind and placebo-controlled crossover study performed at a university hospital clinical research center.

Methods: Ten men with T2DM completed two study days: I) 6-h UAG (1 microgram/kg/h) infusion and II) 6-h placebo (PL) infusion. The patients were investigated in the basal postabsorptive state for 4 hours followed by a hyperinsulinemic clamp for 2 hours. The turnover rates of glucose and fatty acids were assayed by isotope tracer techniques. Energy expenditure was measured by indirect calorimetry.

Results: Plasma UAG was 64.1 ± 11.3 pg/ml at baseline and increased more than 50-fold during UAG infusion. Plasma glucose was 7.0 ± 0.3 [UAG] vs. 6.7 ± 0.4 [PL] mmol/l (P = 0.43) at baseline and was not affected by UAG. During the hyperinsulinemic clamp, glucose infusion rates were 4.69 ± 0.56 [UAG] vs. 4.98 ± 0.43 [PL] mg/kg/min (P = 0.66). UAG did not affect either glucose oxidation, non-oxidative glucose disposal, lipolysis, energy expenditure, or respiratory exchange rate.

Conclusions: This study demonstrates that native UAG exposure does not exert acute metabolic effects in men with T2DM.

TidsskriftJournal of Clinical Endocrinology and Metabolism
Sider (fra-til)2435-2442
Antal sider8
StatusUdgivet - jun. 2019

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