Autonomic dysfunction of the β-cell and the pathogenesis of obesity

In this review, we describe and characterize a specific subtype of obesity with organic underpinnings. There is evidence for etiology (vagal modulation of β-cell depolarization), pathogenesis (insulin hypersecretion), diagnosis (insulin dynamics during OGTT), and treatment (insulin suppression through β-cell somatostatin receptor agonism). Although the number of obese patients with organic VMH damage is exceedingly small, the numbers of subjects who may manifest similar pathogeneses, with either a genetic, neural, or hormonal etiology, may be much greater. Studies are now underway to determine the incidence of this disorder, and the best method for diagnosis and treatment. This recognition of this syndrome of autonomic dysfunction of β-cell insulin secretion is an important first step in improving the nosology of obesity, tying the hypothalamus to the adipocyte, and trying to correlate biochemistry with human behavior. In doing so, it is anticipated that the clinical evaluation of obesity will take a more scientific tone in the near future.