Is Hypothalamic Dysfunction a Cause of Type II Diabetes Mellitus?

BACKGROUND A number of factors contribute to the development of diabetes mellitus, but until recently, the role of hypothalamic dysfunction in the development of this disorder has not received sufficient attention. Hypothalamic neurons that project to the autonomic nervous system control overall glucose metabolism and insulin sensitivity. These neurons, in turn, are controlled by specialized astrocytes possessing proteins that enable them to function as nutrient sensors for glucose and fatty acids. An aging-related pathological process (that of mitochondrial degeneration) is present in these specific hypothalamic astrocytes. This mitochondrial degeneration can be accelerated by access to a high-fat diet, which also induces hypothalamic resistance to leptin, generalized insulin resistance, and an abnormal glucose homeostasis. An impaired astrocyte-neuron signaling, caused by this pathological mitochondrial degeneration, may underlie an abnormal hypothalamic function that leads to the development of type II diabetes. Pharmacological agents that protect astrocytes from mitochondrial degeneration may have a place in the treatment of type II diabetes.

SUMMARY This article reviews evidence that hypothalamic pathology may make an important contribution to the etiology of type II diabetes mellitus.

KEY MESSAGES abnormalities in hypothalamic astrocytes provokes a disturbed hypothalamic function that contributes to the development of diabetes mellitus.