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Endocrinology Vol. 139, No. 11 4540-4546
Copyright © 1998 by The Endocrine Society

ARTICLES

Insulin, But Not Glucose Lowering Corrects the Hyperglucagonemia and Increased Proglucagon Messenger Ribonucleic Acid Levels Observed in Insulinopenic Diabetes1

Eric Dumonteil2, Christophe Magnan2, Beate Ritz-Laser, Paolo Meda, Philippe Dussoix, Marc Gilbert, Alain Ktorza and Jacques Philippe

Unité de Diabétologie Clinique, Department of Medicine (E.D., B.R.-L., P.D., J.P.), and the Department of Morphology (P.M.), Centre Médical Universitaire, 1211 Geneva 4, Switzerland; and Laboratoire de Physiopathologie de la Nutrition, Centre National de la Recherche Scientifique, URA 307, Université Paris 7-Denis Diderot (C.M., M.G., A.K.), 75005 Paris, France

Address all correspondence and requests for reprints to: Jacques Philippe, M.D., Unité de Diabétologie Clinique, Centre Médical Universitaire, 1 rue Michel Servet, CH-1211 Geneva 4, Switzerland. E-mail: philippe{at}cmu.unige.ch

The factors that regulate glucagon biosynthesis and proglucagon gene expression are poorly defined. We previously reported that insulin inhibits proglucagon gene expression in vitro. In vivo, however, the effects of insulin on the regulation of the proglucagon gene have been controversial. Furthermore, whether glucose plays any role alone or in conjunction with insulin on proglucagon gene expression is unknown. We investigated the consequences of insulinopenic diabetes on glucagon gene expression in the endocrine pancreas and intestine and whether insulin and/or glucose could correct the observed abnormalities. We show here that in the first 3 days after induction of hyperglycemia by streptozotocin, rats have levels of plasma glucagon and proglucagon messenger RNA comparable to those of normoglycemic controls despite hyperglycemia. With more prolonged diabetes, plasma glucagon and proglucagon messenger RNA levels increase; this increase is corrected by insulin treatment, but not by phloridzin despite normalization of the glycemia by both treatments. Proglucagon gene expression exhibits the same regulatory response to glucose and insulin in both pancreas and ileum. We conclude that insulin tonically inhibits proglucagon gene expression in the pancreas and ileum and that glucose plays a minor, if any, role in this regulation.




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