Enhanced gluconeogenesis and hepatic insulin resistance in insulin-like growth factor binding protein-1 transgenic mice

Fasting hyperglycemia is observed in transgenic mice which overexpress insu lin-like growth factor binding protein-1. In an attempt to understand the m echanisms underlying this observation we have examined glycogenolysis and g luconeogenesis in isolated hepatocytes from wild-type and transgenic mice. Glucose production from pyruvate was significantly less responsive to inhib ition by insulin in hepatocytes from transgenic mice compared to hepatocyte s from wild-type mice. Serum from transgenic mice resulted in more glucose production by hepatocytes than serum from wild-type mice. Serum alanine was increased while serum lactate was significantly reduced in transgenic mice compared to wild-type mice. Serum free fatty acids and beta-hydroxybutyrat e were similar in both groups of mice. These data suggest that fasting hype rglycemia is due to enhanced gluconeogenesis, hepatic insulin resistance an d increased serum gluconeogenic substrate in transgenic mice. (C) 1999 Else vier Science B.V. All rights reserved.