The hexosamine signaling pathway: a new road to drug discovery
- 1 April 2002
- journal article
- diabetes and-the-endocrine-pancreas
- Published by Wolters Kluwer Health in Current Opinion in Endocrinology, Diabetes and Obesity
- Vol. 9 (2) , 160-167
- https://doi.org/10.1097/00060793-200204000-00006
Abstract
Hyperglycemia is a pathophysiologic state that can perpetuate and sustain the elevated blood glucose levels in type 2 diabetes mellitus by worsening the underlying insulin resistance and impairing insulin secretion. Prolonged hyperglycemia leads to retinopathy, nephropathy, neuropathy, and other vascular disorders. The hexosamine signaling pathway is now known to detect hyperglycemic conditions and mediate induction of insulin resistance and regulation of gene expression. However, the mechanism(s) underlying this novel glucose-sensing pathway require elucidation. The prevailing hypothesis is that the cellular actions of hexosamine signaling are closely linked to O-linked glycosylation of cytosolic and nuclear proteins. In this review, the author discusses recent advances in the field and highlights potential pitfalls in the design and interpretation of some current hexosamine studies. The author also offers suggestions on terminology to facilitate future studies. Understanding the cellular mechanisms underlying hyperglycemia-induced insulin resistance and the progressive development of glucose-mediated diabetic complications will facilitate the discovery of novel drugs to treat diabetes.Keywords
This publication has 33 references indexed in Scilit:
- Glycan‐dependent signaling: O‐linked N‐acetylglucosamineThe FASEB Journal, 2001
- Overexpression of glutamine: fructose-6-phosphate amidotransferase in the liver of transgenic mice results in enhanced glycogen storage, hyperlipidemia, obesity, and impaired glucose tolerance.Diabetes, 2000
- Transgenic mice with increased hexosamine flux specifically targeted to beta-cells exhibit hyperinsulinemia and peripheral insulin resistance.Diabetes, 2000
- Glucosamine infusion in rats mimics the β-cell dysfunction of non—insulin-dependent diabetes mellitusMetabolism, 1998
- Overexpression of glutamine:fructose-6-phosphate amidotransferase in transgenic mice leads to insulin resistance.Journal of Clinical Investigation, 1996
- Glucosamine induces insulin resistance in vivo by affecting GLUT 4 translocation in skeletal muscle. Implications for glucose toxicity.Journal of Clinical Investigation, 1995
- In vivo glucosamine infusion induces insulin resistance in normoglycemic but not in hyperglycemic conscious rats.Journal of Clinical Investigation, 1995
- In vivo effects of glucosamine on insulin secretion and insulin sensitivity in the rat: Possible relevance to the maladaptive responses to chronic hyperglycaemiaDiabetologia, 1995
- Pre-exposure to glucosamine induces insulin resistance of glucose transport and glycogen synthesis in isolated rat skeletal muscles. Study of mechanisms in muscle and in rat-1 fibroblasts overexpressing the human insulin receptorDiabetes, 1993
- New insights into the metabolic regulation of insulin action and insulin resistance: role of glucose and amino acidsThe FASEB Journal, 1991