This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Guo, Y. Articles by Liu, J.-L. Search for Related Content PubMed PubMed Citation Articles by Guo, Y. Articles by Liu, J.-L.

Pancreatic Islet-Specific Expression of an Insulin-Like Growth Factor-I Transgene Compensates Islet Cell Growth in Growth Hormone Receptor Gene-Deficient Mice

Fraser Laboratories (Y.G., Y.L., K.R., Z.T., Y.L.L., J.-L.L.), Department of Medicine, McGill University, Montreal, Quebec, Canada H3A 1A1; Transgenic Unit (D.H.), Montreal General Hospital Research Institute, Montreal, Quebec, Canada H3G 1A4; and Edison Biotechnology Institute and Department of Biomedical Sciences (J.J.K.), College of Osteopathic Medicine, Ohio University, Athens, Ohio 45701

Address all correspondence and requests for reprints to: Dr. Jun-Li Liu, Fraser Laboratories, Room M3-15, Royal Victoria Hospital, 687 Pine Avenue West, Montreal, Quebec, Canada H3A 1A1. E-mail: jun-li.liu{at}mcgill.ca.

Both GH and IGF-I stimulate islet cell growth, inhibit cell apoptosis, and regulate insulin biosynthesis and secretion. GH receptor gene deficiency (GHR^–/–) caused diminished pancreatic islet cell mass and serum insulin level and elevated insulin sensitivity. Because IGF-I gene expression was nearly abolished in these mice, we sought to determine whether that had caused the islet defects. To restore IGF-I level, we have generated transgenic mice that express rat IGF-I cDNA under the direction of rat insulin promoter 1 (RIP-IGF). Using RNase protection assay and immunohistochemistry, the IGF-I transgene expression was revealed specifically in pancreatic islets of the RIP-IGF mice, which exhibited normal growth and development and possess no abnormalities in glucose homeostasis, insulin production, and islet cell mass. GHR^–/– mice exhibited 50% reduction in the ratio of islet cell mass to body weight and increased insulin sensitivity but impaired glucose tolerance. Compared with GHR^–/– alone, IGF-I overexpression on a GHR^–/– background caused no change in the diminished blood glucose and serum insulin levels, pancreatic insulin contents, and insulin tolerance but improved glucose tolerance and insulin secretion. Remarkably, islet-specific overexpression of IGF-I gene in GHR^–/– mice restored islet cell mass, at least partially through cell hypertrophy. Interestingly, double-transgenic male mice demonstrated a transient rescue in growth rates vs. GHR^–/– alone, at 2–3 months of age. Our results suggest that IGF-I deficiency is part of the underlying mechanism of diminished islet growth in GHR^–/– mice and are consistent with the notion that IGF-I mediates GH-induced islet cell growth.

This article has been cited by other articles:

				K. Robertson, Y. Lu, K. De Jesus, B. Li, Q. Su, P. K. Lund, and J.-L. Liu A general and islet cell-enriched overexpression of IGF-I results in normal islet cell growth, hypoglycemia, and significant resistance to experimental diabetes Am J Physiol Endocrinol Metab, May 1, 2008; 294(5): E928 - E938. [Abstract] [Full Text] [PDF]

				K. Robertson, J. J. Kopchick, and J.-L. Liu Growth hormone receptor gene deficiency causes delayed insulin responsiveness in skeletal muscles without affecting compensatory islet cell overgrowth in obese mice Am J Physiol Endocrinol Metab, September 1, 2006; 291(3): E491 - E498. [Abstract] [Full Text] [PDF]