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

Abstract

Background Aerobic 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. Methods Participants 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/m 2 /min) hyperinsulinemic clamp (ISO-clamp) to assess SGU and insulin-mediated suppression of EGP, respectively. After the intervention period, both tests were repeated. Results In 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). Conclusions In 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.

Plasma Interleukin-10 and Cholesterol Levels May Inform about Interdependences between Fitness and Fatness in Healthy Individuals

“…Fitness has been shown to play an important role in protecting against glucose intolerance [ 43 ]. This may be related to the well-known effect of muscle contractile activity, hence exercise training, on insulin sensitivity [ 44 ].…”

Exercise-Induced Improvements to Whole Body Glucose Metabolism in Type 2 Diabetes: The Essential Role of the Liver

“…The results showed that the percent of the oral glucose taken up by the splanchnic tissues increased from 38 to 50% within the collapsed group. In a more recent study, Gregory et al ( 50 ) studied the effect of 15 weeks of aerobic exercise training without weight loss (70% VO 2 max, 4–5 days/week, 50 min/day) on SGU in patients with T2D. In addition to observing that insulin-mediated suppression of EGP was improved in the same group of patients after exercise training, it was reported that SGU in response to a 75-gram oral glucose load decreased from 23 grams to 9 grams.…”

“…In addition to the previously noted results by Bogardus et al ( 43 ), Segal et al ( 45 ) observed that fasting HGP was lower in patients with T2D after 12 weeks of aerobic exercise training (4x/week, 1 h/day, 70% VO 2 max) without weight loss. On the other hand, most other studies in patients with T2D that used aerobic exercise training durations of 6 weeks or more report that fasting EGP does not change ( 46 , 48 – 50 ), even those that incorporate significant weight loss into their study design ( 48 , 49 ). The reason for this discrepancy is not entirely clear, but this is not to say that subjects with T2D from these latter studies did not demonstrate improved hepatic function as a result of exercise training.…”

“…The reason for this discrepancy is not entirely clear, but this is not to say that subjects with T2D from these latter studies did not demonstrate improved hepatic function as a result of exercise training. In fact, all but one of these studies [which was the only one that showed a lowering of fasting EGP ( 45 )], utilizing an exercise training duration >6 weeks showed that after training, the suppression of EGP by insulin was improved ( 43 , 46 , 48 – 50 ). Thus, although the manifestations may differ slightly between studies, it is clear that sufficient training durations result in improved hepatic glucose metabolism in patients with T2D, with the most common effect being enhanced suppression of EGP by physiological levels of insulin.…”

C-peptide enhances glucagon secretion in response to hyperinsulinemia under euglycemic and hypoglycemic conditions

“…A portion of the regulation of glucagon secretion has been ascribed to an inhibitory effect of insulin on glucagon secretion, also known as the intra-islet hypothesis (14,15). In fact, the intravenous (IV) infusion of insulin during euglycemia has been shown to lower glucagon levels in dogs (16), healthy humans (17)(18)(19)(20), and patients with diabetes (21)(22)(23). In contrast, endogenous insulin secretion, such as occurs after a meal, does not have the same inhibitory effect on glucagon levels (24), thereby raising the possibility that endogenous insulin regulates glucagon secretion differently than IV insulin.…”