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Current Insights and New Perspectives on the Roles of Hyperglucagonemia in Non-Insulin–Dependent Type 2 Diabetes

  • Hypertension Management and Antihypertensive Drugs (HM Siragy and B Waeber, Section Editors)
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Abstract

Type 2 diabetes is well recognized as a noninsulin-dependent diabetic disease. Clinical evidence indicates that the level of circulating insulin may be normal, subnormal, and even elevated in type 2 diabetic patients. Unlike type 1 diabetes, the key problem for type 2 diabetes is not due to the absolute deficiency of insulin secretion, but because the body is no longer sensitive to insulin. Thus, insulin resistance is increased and the sensitivity to insulin is reset, so increasing levels of insulin are required to maintain body glucose and metabolic homeostasis. How insulin resistance is increased and what factors contribute to its development in type 2 diabetes remain incompletely understood. Overemphasis of insulin deficiency alone may be too simplistic for us to understand how type 2 diabetes is developed and should be treated, since glucose metabolism and homeostasis are tightly controlled by both insulin and glucagon. Insulin acts as a YIN factor to lower blood glucose level by increasing cellular glucose uptake, whereas glucagon acts as a YANG factor to counter the action of insulin by increasing glucose production. Furthermore, other humoral factors other than insulin and glucagon may also directly or indirectly contribute to increased insulin resistance and the development of hyperglycemia. The purpose of this article is to briefly review recently published animal and human studies in this field, and provide new insights and perspectives on recent debates as to whether hyperglucagonemia and/or glucagon receptors should be targeted to treat insulin resistance and target organ injury in type 2 diabetes.

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Acknowledgments

The authors’ work was supported in part by the National Institute of Diabetes, Digestive and Kidney Diseases Grants (5RO1DK067299, 2R56057299, and 2RO1DK067299.A2). The authors apologize to those investigators whose excellent work is not cited due to space and scope restrictions.

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Conflict of Interest

Xiao C. Li and Jia L. Zhuo declare that they have no conflict of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human subjects performed by any of the authors. All animal experiments as described in the work of the authors in this manuscript were approved by the Institutional Animal Care and Use Committees of Henry Ford Health System, Detroit, Michigan, and the University of Mississippi Medical Center, Jackson, Mississippi, USA.

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  1. Laboratory of Receptor and Signal Transduction, Department of Pharmacology & Toxicology, University of Mississippi Medical Center, Jackson, MS, 39216, USA

    Xiao C. Li & Jia L. Zhuo

  2. Department of Pharmacology and Toxicology, University of Mississippi Medical Center, 2500 North State Street, Jackson, MS, 39216-4505, USA

    Jia L. Zhuo

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Li, X.C., Zhuo, J.L. Current Insights and New Perspectives on the Roles of Hyperglucagonemia in Non-Insulin–Dependent Type 2 Diabetes. Curr Hypertens Rep 15, 522–530 (2013). https://doi.org/10.1007/s11906-013-0383-y

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