Regulating Glucagon Secretion: Somatostatin in the Spotlight

The regulation of islet hormone secretion in vivo is likely to involve a complex interplay between circulating nutrients, hormones, and neurotransmitters (1). A new study by Hauge-Evans et al. (2) in this issue provides interesting new insights into the contribution of an intraislet paracrine role for somatostatin in the control of insulin, and more especially glucagon, release.

Glucagon is the principal counterregulatory hormone that opposes the anabolic effects of insulin, notably on the liver (3), and a relative excess of glucagon is a hallmark of all forms of diabetes. However, failure to secrete adequate quantities of glucagon in response to insulin-induced hypoglycemia characterizes longstanding type 1 diabetes (4) and is an important contributor to mortality in this disease, accounting for 2–4% of all deaths (5).

Glucagon is stored alongside insulin in the islet, albeit in a discrete cellular compartment, the pancreatic α-cell. Just as the metabolic actions of glucagon oppose those of insulin, the regulators of insulin's release (1) tend to exert opposing effects on glucagon secretion (6). Thus, elevated concentrations of glucose suppress glucagon release, while catecholamines stimulate the secretion of this hormone. Acting independently of these mechanisms, neuronal inputs into the islet exert a further important level of control over glucagon release (7).

Despite being a subject under investigation for more than 35 years (6), just how the effects of glucose are achieved at the level of individual α-cells is still disputed and has become an area of vigorous research in recent times (Figure 1). As yet, however, a consensus has not been reached. Several laboratories (e.g., 8), including the author's (9), have concluded that glucose acts directly on isolated mouse α-cells to suppress oscillations in intracellular free Ca²⁺ concentration in …