Aerobic exercise training improves hepatic and muscle insulin sensitivity, but reduces splanchnic glucose uptake in obese humans with type 2 diabetes

Justin M Gregory,Jason J Winnick,E Patrick Donahue,Brian G Engelhardt,Dale S Edgerton,Pam Marks-Shulman,James A Muldowney,Heidi J Silver,Regina Tyree

doi:10.1038/s41387-019-0090-0

Justin M Gregory, Jason J Winnick + Show 7 more

Open Access

https://doi.org/10.1038/s41387-019-0090-0

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Abstract

BackgroundAerobic exercise training is known to have beneficial effects on whole-body glucose metabolism in people with type 2 diabetes (T2D). The responses of the liver to such training are less well understood. The purpose of this study was to determine the effect of aerobic exercise training on splanchnic glucose uptake (SGU) and insulin-mediated suppression of endogenous glucose production (EGP) in obese subjects with T2D.MethodsParticipants included 11 obese humans with T2D, who underwent 15 ± 2 weeks of aerobic exercise training (AEX; n = 6) or remained sedentary for 15 ± 1 weeks (SED; n = 5). After an initial screening visit, each subject underwent an oral glucose load clamp and an isoglycemic/two-step (20 and 40 mU/m2/min) hyperinsulinemic clamp (ISO-clamp) to assess SGU and insulin-mediated suppression of EGP, respectively. After the intervention period, both tests were repeated.ResultsIn AEX, the ability of insulin to suppress EGP was improved during both the low (69 ± 9 and 80 ± 6% suppression; pre-post, respectively; p < 0.05) and high (67 ± 6 and 82 ± 4% suppression, respectively; p < 0.05) insulin infusion periods. Despite markedly improved muscle insulin sensitivity, SGU was reduced in AEX after training (22.9 ± 3.3 and 9.1 ± 6.0 g pre-post in AEX, respectively; p < 0.05).ConclusionsIn obese T2D subjects, exercise training improves whole-body glucose metabolism, in part, by improving insulin-mediated suppression of EGP and enhancing muscle glucose uptake, which occur despite reduced SGU during an oral glucose challenge.

Highlights

Introduction Type2 diabetes (T2D) is a metabolic disease characterized by the dysfunction of several key glucoregulatory organs during the fasted state and in response to glucose ingestion[1]
Subjects who participated in the study included six obese people with type 2 diabetes, that performed aerobic exercise for 15 ± 2 weeks (AEX) and five subjects with T2D who remained sedentary for the same length of time (SED; 15 ± 1 weeks)
As opposed to SED, whose hemoglobin A1C did not change (n = 4 in SED for this measure), hemoglobin A1C was lower in aerobic exercise training (AEX) after the study (p < 0.05; n = 6), thereby indicating that the training program had a beneficial effect on whole-body glucose metabolism

Summary

Introduction

2 diabetes (T2D) is a metabolic disease characterized by the dysfunction of several key glucoregulatory organs during the fasted state and in response to glucose ingestion[1]. Among these organs, impaired glucose metabolism by the liver is recognized as an important contributor to T2D because of the central role it plays in the regulation of both fasting glucose levels and glucose tolerance. Insulin signaling is important for normal liver function during the postprandial state because it promotes hepatic glucose uptake and glycogen deposition, a complex process that accounts for the disposal of one-third of ingested carbohydrate[4,5,6,7,8,9]. The purpose of this study was to determine the effect of aerobic exercise training on splanchnic glucose uptake (SGU) and insulinmediated suppression of endogenous glucose production (EGP) in obese subjects with T2D

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