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Endocrine Abstracts (2015) 37 GP17.03 | DOI: 10.1530/endoabs.37.GP.17.03

1Department of Endocrinology, Diabetes and Nutrition, Charité-University Medicine Berlin, Berlin, Germany; 2Department of Clinical Nutrition, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany; 3Department of Endocrinology, Diabetes and Nutrition at the Center for Cardiovascular Research (CCR), Charité-University Medicine Berlin, Berlin, Germany; 4Warwickshire Institute for the Study of Diabetes, Endocrinology and Metabolism,University Hospitals Coventry and Warwickshire NHS Trust, Coventry, UK; 5Division of Metabolic & vascular Health, Warwick Medical School, University of Warwick, Coventry, UK; 6Medical Research Laboratories, Institute of Clinical Medicine, Faculty of Health Sciences, Aarhus University, DK-8000 Aarhus C, Aahrus, Denmark; 7Department of Endocrinology, Diabetes and Nutrition at the Experimental and Clinical Research Center (ECRC), Charité-University Medicine Berlin and Max-Delbrück Centre Berlin-Buch,, Berlin, Germany; 8Section of Metabolic Vascular Medicine,Medical Clinic III, University Clinic Dresden, Dresden, Germany.

Background: The mechanisms underlying the association between severe hypoglycaemia and increased cardiovascular mortality among patients with diabetes mellitus are not fully understood. Our aim was to evaluate changes in GH/IGF1 axis during insulin-induced hypoglycaemia, as a possible link.

Methods: Twenty-five healthy subjects, 12 obese participants (OP; 6/ 6; 34.4±1.7 kg/m2), and 13 healthy lean participants (LP; 6/ 7; 21.7±0.6 kg/m2) were studied using insulin tolerance test and changes in GH, total IGF1, IGF binding proteins (IGFBPs) and IGF1 bioactivity, measured by the cell-based KIRA method, were investigated. Moreover, the effect of insulin on mRNA expression of parts of the GH/IGF1 system was further studied in mouse primary hepatocytes.

Results: Under hypoglycaemic conditions, insulin significantly increased IGFBP2 and decreased IGF1 bioactivity in both groups (P<0.01). This was followed by a surge in GH (P<0.01). As expected, insulin decreased IGFBP1 levels, whereas no changes in total IGF1 and IGFBP3 levels were observed. In vitro, insulin stimulation of primary hepatocytes lead to a decrease of IGFBP1 and IGFBP3 and increase of IGFBP2 mRNA expression.

Conclusion: The insulin-induced hypoglycaemia is associated with a decrease in IGF1 bioactivity through up-regulation of IGFBP2. Our results point to a possible and previously poorly explored mechanism explaining the strong association between hypoglycaemia and increased cardiovascular mortality among diabetic patients.

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