Exp Clin Endocrinol Diabetes 2020; 128(08): 520-527
DOI: 10.1055/a-0808-4029
Article

Peripheral Insulin Extraction in Non-Diabetic Subjects and Type 2 Diabetes Mellitus Patients

Daniël H. van Raalte
1   Department of Internal Medicine, Spaarne Gasthuis, Haarlem, The Netherlands
2   Department of Internal Medicine, Diabetes Center, VU University Medical Center, Amsterdam, The Netherlands
,
Eva van der Palen
1   Department of Internal Medicine, Spaarne Gasthuis, Haarlem, The Netherlands
,
Pauline Idema
1   Department of Internal Medicine, Spaarne Gasthuis, Haarlem, The Netherlands
,
Liza Wong
3   Department of Cardiology, Spaarne Gasthuis, Haarlem, The Netherlands
,
Sander W. M. Keet
1   Department of Internal Medicine, Spaarne Gasthuis, Haarlem, The Netherlands
,
Mariska Vlot
1   Department of Internal Medicine, Spaarne Gasthuis, Haarlem, The Netherlands
,
Raymond Tukkie
3   Department of Cardiology, Spaarne Gasthuis, Haarlem, The Netherlands
,
Bob van Vlies
3   Department of Cardiology, Spaarne Gasthuis, Haarlem, The Netherlands
,
Erik H. Serné
2   Department of Internal Medicine, Diabetes Center, VU University Medical Center, Amsterdam, The Netherlands
,
Reinier W. ten Kate
1   Department of Internal Medicine, Spaarne Gasthuis, Haarlem, The Netherlands
› Author Affiliations

Abstract

Background Insulin has to be transported across the capillary endothelium to stimulate muscle glucose uptake. We investigated insulin uptake from the peripheral circulation in non-diabetic (ND) individuals and in type 2 diabetes (T2D) patients.

Methods Single-center cross-sectional study involving 40 ND (age 65±11 years) and 30 T2D patients (age 67±8 years). Thirty-six participants were studied in the fasted state (22 ND subjects and 14 T2D patients termed NDF and T2DF) and 34 participants 1-h following a glucose challenge (18 ND subjects and 16 T2D patients indicated as NDG and T2DG). Main outcome measure was fractional extraction (FE) of insulin (FEins) and glucose using the forearm balance method.

Results In NDF, FEins was 18 (10–26) % at lower insulin levels (63 51–80] pmol/l), while in NDG at higher insulin levels (776 [543–1176] pmol/l), FEins was 9 (4–16) % (p = 0.01 vs. NDF). In NDF only, a negative correlation was observed between FEins and arterial plasma insulin load (rho = − 0.575;p = 0.006) and fasting plasma glucose levels (rho = − 0.551;p = 0.01). In T2DF FEins was 6 (1–19) % and not different from FEins in T2DG (10 2–14) %), and was not associated to fasting glucose. FEins tended to be higher in NDF compared to T2DF (p = 0.07).

Discussion We propose that in ND individuals, besides passive diffusion, an active high-affinity pathway with limited capacity around lower physiologic insulin levels exists for insulin transendothelial transport, contributing to glycemic control. In T2D patients, this mechanism of peripheral insulin uptake is diminished or even absent. Modulation of insulin extraction from the circulation may be a novel target to improve glucose metabolism in T2D.



Publication History

Received: 06 August 2018
Received: 23 October 2018

Accepted: 27 November 2018

Article published online:
17 December 2018

© Georg Thieme Verlag KG
Stuttgart · New York

 
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