caa a22 4500 475773101 CHVBK 20180406123623.0 cr unu---uuuuu 170329e20001001xx s 000 0 eng 10.1007/s001250051540 doi (NATIONALLICENCE)springer-10.1007/s001250051540 Stimulatory effect of increased non-esterified fatty acid concentrations on proinsulin processing in healthy humans [Elektronische Daten] [N. Stefan, A. Fritsche, A. Madaus, H. Häring, M. Stumvoll] Aims/hypothesis. To assess the effect of increased concentrations of non-esterified fatty acids (NEFA) on proinsulin processing in healthy humans.¶Methods. We did a hyperglycaemic clamp (130 min duration, 8 mmol/l glucose, with a 5-g arginine bolus at min 120) before and after a 5-h infusion of Intralipid/heparin in 14 healthy subjects. Of the subjects eight underwent a saline control experiment. The proinsulin : insulin (PI:I) ratio immediately after the arginine bolus (122.5 to 125 min) was considered to provide an estimate for the conversion of proinsulin to insulin in the beta cell.¶Results. Concentrations of NEFA were 757 ± 86 μmol/l and 1669 ± 134 μmol/l (p < 0.001) after the 5-h infusion of saline or Intralipid, respectively. Insulin secretion rates were no different between the Intralipid and saline infusions (p = 0.73). There was no statistically significant difference for either the proinsulin concentration or the PI:I ratio during glucose stimulation alone (0 to 120 min). In response to arginine, in contrast, proinsulin remained unchanged during the saline infusion (from 31 ± 6 to 29 ± 7 pmol/l, p = 0.50) but decreased during 5 h of lipid infusion from (21 ± 3 to 15 ± 2 pmol/l, p = 0.02). The PI:I ratio in response to the arginine bolus was higher during the saline infusion (2.0 ± 0.2 % vs 1.7 ± 0.2 %, p = 0.04) but decreased during the Intralipid infusion (from 1.6 ± 0.2 % to 1.2 ± 0.1 %, p = 0.04).¶Conclusion/interpretation. The statistically significantly lower PI:I ratio in response to arginine during experimentally increased concentrations of NEFA suggests that NEFA increase the conversion of proinsulin to insulin in humans in vivo. [Diabetologia (2000) 43: 1368-1373] Springer-Verlag Berlin Heidelberg, 2000 Keywords Insulin secretion, proinsulin secretion, non-esterified fatty acids, glucose, arginine nationallicence Stefan N. Medical Clinic, Department of Endocrinology, Metabolism and Pathobiochemistry, Eberhard-Karls-University, Tübingen, Germany, DE aut Fritsche A. Medical Clinic, Department of Endocrinology, Metabolism and Pathobiochemistry, Eberhard-Karls-University, Tübingen, Germany, DE aut Madaus A. Medical Clinic, Department of Endocrinology, Metabolism and Pathobiochemistry, Eberhard-Karls-University, Tübingen, Germany, DE aut Häring H. Medical Clinic, Department of Endocrinology, Metabolism and Pathobiochemistry, Eberhard-Karls-University, Tübingen, Germany, DE aut Stumvoll M. Medical Clinic, Department of Endocrinology, Metabolism and Pathobiochemistry, Eberhard-Karls-University, Tübingen, Germany, DE aut https://doi.org/10.1007/s001250051540 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s001250051540 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Stefan N. Medical Clinic, Department of Endocrinology, Metabolism and Pathobiochemistry, Eberhard-Karls-University, Tübingen, Germany, DE aut NATIONALLICENCE 700 1- Fritsche A. Medical Clinic, Department of Endocrinology, Metabolism and Pathobiochemistry, Eberhard-Karls-University, Tübingen, Germany, DE aut NATIONALLICENCE 700 1- Madaus A. Medical Clinic, Department of Endocrinology, Metabolism and Pathobiochemistry, Eberhard-Karls-University, Tübingen, Germany, DE aut NATIONALLICENCE 700 1- Häring H. Medical Clinic, Department of Endocrinology, Metabolism and Pathobiochemistry, Eberhard-Karls-University, Tübingen, Germany, DE aut NATIONALLICENCE 700 1- Stumvoll M. Medical Clinic, Department of Endocrinology, Metabolism and Pathobiochemistry, Eberhard-Karls-University, Tübingen, Germany, DE aut Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer