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Diabetes 54:952-958, 2005
© 2005 by the American Diabetes Association, Inc.

Acute Induction of Gene Expression in Brain and Liver by Insulin-Induced Hypoglycemia

Jason W. Mastaitis1, Elisa Wurmbach2,3, Hui Cheng1, Stuart C. Sealfon1,2, and Charles V. Mobbs1

1 Fishberg Center for Neurobiology, Mount Sinai School of Medicine, New York, New York
2 Department of Neurology, Mount Sinai School of Medicine, New York, New York
3 Department of Medicine, Division of Hematology/Oncology, Mount Sinai School of Medicine, New York, New York

The robust neuroendocrine counterregulatory responses induced by hypoglycemia protect the brain by restoring plasma glucose, but little is known about molecular responses to hypoglycemia that may also be neuroprotective. To clarify these mechanisms, we examined gene expression in hypothalamus, cortex, and liver 3 h after induction of mild hypoglycemia by a single injection of insulin, using cDNA microarray analysis and quantitative real-time PCR. Real-time PCR corroborated the induction of six genes (angiotensinogen, GLUT-1, inhibitor of {kappa}B, inhibitor of DNA binding 1 [ID-1], Ubp41, and mitogen-activated protein kinase phosphatase-1 [MKP-1]) by insulin-induced hypoglycemia in the hypothalamus: five of these six genes in cortex and three (GLUT-1, angiotensinogen, and MKP-1) in liver. The induction was due to hypoglycemia and not hyperinsulinemia, since fasting (characterized by low insulin and glucose) also induced these genes. Four of these genes (angiotensinogen, GLUT-1, ID-1, and MKP-1) have been implicated in enhancement of glucose availability, which could plausibly serve a neuroprotective role during acute hypoglycemia but, if persistent, could also cause glucose-sensing mechanisms to overestimate plasma glucose levels, potentially causing hypoglycemia-induced counterregulatory failure. Although using cDNA microarrays with more genes, or microdissection, would presumably reveal further responses to hypoglycemia, these hypoglycemia-induced genes represent useful markers to assess molecular mechanisms mediating cellular responses to hypoglycemia.

Address correspondence and reprint requests to Charles V. Mobbs, PhD, Neurobiology of Aging Laboratories, Box 1639, Mount Sinai School of Medicine, One Gustave Levy Place, New York, NY 10029. E-mail: charles.mobbs{at}mssm.edu


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