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Increased Insulin Sensitivity Is Associated with Reduced Insulin and Glucagon Secretion and Increased Insulin Clearance in Man

Department of Medicine (B.A.), Lund University, Lund SE-221 84; and Department of Clinical Physiology (O.T.), Lund University, SE-20501 Malmö, Sweden

Address all correspondence and requests for reprints to: Dr. Bo Ahrén, Department of Medicine, Lund University, B11 BMC, SE-221 84 Lund, Sweden. E-mail: bo.ahren{at}med.lu.se.

Insulin secretion is increased in insulin resistance. In this study, we examined whether high insulin sensitivity results in low insulin secretion. Twelve male master athletes [age 25.6 ± 4.1 (mean ± SD) yr] and seven male sedentary students (age 25.0 ± 2.0 yr) underwent a hyperinsulinemic, euglycemic clamp and a glucose-dependent arginine stimulation test. Athletes had high insulin sensitivity [230 ± 18 vs. 92 ± 12 (nmol glucose/kg·min)/(pmol insulin/liter), P < 0.001] and low insulin response to arginine (at fasting glucose 135 ± 22 vs. 394 ± 60 pmol/liter, P < 0.001), which resulted in unaltered disposition index (32.8 ± 3.8 vs. 33.5 ± 3.3 µmol glucose/kg·min, NS). Also, the C-peptide response to arginine was reduced (at fasting glucose 0.71 ± 0.09 vs. 0.89 ± 0.09 nmol/liter, P = 0.034). However, the C-peptide reduction was not as large as the insulin reduction yielding increased disposition index in athletes when calculated from C-peptide data (184 ± 9 vs. 76 ± 11 µmol glucose/kg·min, P < 0.001). This difference is explained by increased insulin clearance among the athletes during the first 5 min after arginine (81.1% ± 1.8% vs. 53.6% ± 4.7%, P < 0.001). Also, the glucagon response to arginine was reduced in the athletes (58.8 ± 6.7 vs. 90.1 ± 9.9 ng/liter at fasting glucose, P = 0.009). We conclude that high insulin sensitivity results in low islet hormone secretion and increased insulin clearance.

This work was supported by the Swedish Research Council (Grant 6834); Novo Nordisk Foundation; Swedish Diabetes Foundation; Albert Påhlsson Foundation; Lund University Hospital Research Funds; and Faculty of Medicine, Lund University.

Abbreviations: ACR, Acute C-peptide response; AGR, acute glucagon response; AIR, acute insulin response; BMI, body mass index; DI, disposition index; FFA, free fatty acid; M/I value, amount of glucose infused to maintain the glucose level during the clamp study divided by the mean insulin concentration.

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